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• W2316985585 abstract "Lung transplantation (LT) has proven to be successful in carefully selected individuals with end-stage lung disease. However, long-term graft survival post-LT is often hindered by the development of the bronchiolitis obliterans syndrome (BOS). Because BOS represents is a major problem for all LT centers, early identification and prediction of progressive loss of lung function is a major goal. MicroRNAs (miRNAs) play a major role in regulating many cellular functions, including epithelial-to-mesenchymal transition. miRNAs are emerging not only as biomarkers but also as potential therapy. The recognized importance of injured human bronchial epithelium in lung allograft dysfunction indicates that there is a need for research into the potential role of miRNAs. In this we review we summarize published findings in miRNAs implicated in lung and other types of allograft dysfunction and their role in maintaining the phenotype of epithelial cells after transplant injury. We also address potential clinical interventions that involve manipulating miRNA expression that may promote long-term airway integrity and graft survival. Lung transplantation (LT) has proven to be successful in carefully selected individuals with end-stage lung disease. However, long-term graft survival post-LT is often hindered by the development of the bronchiolitis obliterans syndrome (BOS). Because BOS represents is a major problem for all LT centers, early identification and prediction of progressive loss of lung function is a major goal. MicroRNAs (miRNAs) play a major role in regulating many cellular functions, including epithelial-to-mesenchymal transition. miRNAs are emerging not only as biomarkers but also as potential therapy. The recognized importance of injured human bronchial epithelium in lung allograft dysfunction indicates that there is a need for research into the potential role of miRNAs. In this we review we summarize published findings in miRNAs implicated in lung and other types of allograft dysfunction and their role in maintaining the phenotype of epithelial cells after transplant injury. We also address potential clinical interventions that involve manipulating miRNA expression that may promote long-term airway integrity and graft survival. Lung transplantation (LT) has proven to be the only option for carefully selected individuals suffering from a variety of end-stage lung diseases unresponsive or minimally responsive to medical treatment. LT has been performed since the 1960s, although the early attempts had limited success.1Cooper D.K.C. Transplantation of the heart and both lungs I. Historical review.Thorax. 1969; 24: 383-390Crossref PubMed Scopus (19) Google Scholar, 2Calne R.Y. Clinical organ transplantation. Wiley-Blackwell, New York1971Google Scholar Since that time, LT has continued to evolve in terms of application and long-term success and is now a viable treatment.3Orens J.B. Garrity E.R.J. General overview of lung transplantation and review of organ allocation.Proc Am Thorac Soc. 2009; 6: 13-19Crossref PubMed Scopus (87) Google Scholar It has been suggested that complications in the early post-operative survival period seeds the development of progressive pulmonary disorders. Thus, chronic allograft dysfunction is considered one of the most significant problems in LT. Improvements are therefore required for early diagnosis and treatment, which may be facilitated through increased understanding of the pathophysiology involved.4Gottlieb J. Update on lung transplantation.Ther Adv Respir Dis. 2008; 2: 237-247Crossref PubMed Scopus (27) Google Scholar, 5Hartert M. Senbaklavacin O. Gohrbandt B. et al.Lung transplantation: a treatment option in end-stage lung disease.Dtsch Arztebl Int. 2014; 111: 107-116PubMed Google Scholar, 6Suwara M.I. Vanaudenaerde B.M. Verleden S.E. et al.Mechanistic differences between phenotypes of chronic lung allograft dysfunction after lung transplantation.Transpl Int. 2014; 27: 857-867Crossref PubMed Scopus (40) Google Scholar After LT, chronic lung allograft dysfunction (rejection) continues to be a problem despite the advancements in immunosuppressant and surgical techniques. About 60% to 75% recipients have suffered from chronic rejection within 5 years post-LT, which is manifested physiologically as loss of lung function.7Hayes Jr, D. A review of bronchiolitis obliterans syndrome and therapeutic strategies.J Cardiothorac Surg. 2011; 6: 92Crossref PubMed Scopus (59) Google Scholar The development and severity of bronchiolitis obliterans syndrome (BOS) has been characterized by the International Society for Heart and Lung Transplantation (ISHLT) guidelines, which defined the various stages of loss of lung function (Table 1).8Kesten S. Maidenberg A. Winton T. et al.Treatment of presumed and proven acute rejection following six months of lung transplant survival.Am J Respir Crit Care Med. 1991; 152: 1321-1324Crossref Scopus (41) Google ScholarTable 1Five Stages of BOSStage2003 ClassificationBOS 0FEV1 >90% of baseline and FEV25-75 >75% of baselineBOS 0pFEV1 81% to 90% of baseline and/or FEV25-75 ≤75% of baselineBOS 1FEV1 66% to 80% of baselineBOS 2FEV1 51% to 65% of baselineBOS 3FEV1 ≤50% of baselineThe baseline FEV1 and FEV25-75 values were recorded as the average of the 2 highest FEV values without the use of a bronchodilator at 3 weeks post-transplant. The progressive stages of BOS correlate with declining airflow obstruction. BOS 0p (potential BOS) gives an indication of an early decline in lung function.8Kesten S. Maidenberg A. Winton T. et al.Treatment of presumed and proven acute rejection following six months of lung transplant survival.Am J Respir Crit Care Med. 1991; 152: 1321-1324Crossref Scopus (41) Google Scholar BOS, bronchiolitis obliterans syndrome; FEV, forced expiratory volume in 1 second. Open table in a new tab The baseline FEV1 and FEV25-75 values were recorded as the average of the 2 highest FEV values without the use of a bronchodilator at 3 weeks post-transplant. The progressive stages of BOS correlate with declining airflow obstruction. BOS 0p (potential BOS) gives an indication of an early decline in lung function.8Kesten S. Maidenberg A. Winton T. et al.Treatment of presumed and proven acute rejection following six months of lung transplant survival.Am J Respir Crit Care Med. 1991; 152: 1321-1324Crossref Scopus (41) Google Scholar BOS, bronchiolitis obliterans syndrome; FEV, forced expiratory volume in 1 second. It is postulated that early graft injury and acute rejection contributes to the development of progressive graft deterioration and chronic rejection. Development of the pathology thought to underlie BOS involves the release of cytokines, chemokines and growth factors from the allograft airway due to repetitive tissue injury, which forms a positive feedback system (Figure 1). This leads to recruitment of immune cells at the site of injury and an influx of mononuclear phagocytes and T cells that cumulatively induce inflammatory responses promoting epithelial damage. These inflammatory responses stimulate epithelial cells to undergo repair and vascular remodeling that ultimately leads to fibrosis.9Neuringer I. Medaiyese A. McNeillie P. et al.New insights into acute and chronic lung rejection.Curr Respir Med Rev. 2008; 4: 40-51Crossref Scopus (1) Google Scholar, 10Song M.K. De Vito Dabbs A. Studer S.M. et al.Course of illness after the onset of chronic rejection in lung transplant recipients.Am J Crit Care. 2008; 17: 246-253PubMed Google Scholar, 11Holbro A. Lehmann T. Girsberger S. et al.Lung histology predicts outcome of bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation.Biol Blood Marrow Transplant. 2013; 19: 973-980Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar The etiology of chronic allograft dysfunction is mediated by both alloimmune and non-alloimmune mechanisms. Acute cellular rejection (ACR) is one of the major alloimmune-dependent risk factors responsible for the development of BOS.12Mangi A.A. Mason D.P. Nowicki E.R. et al.Predictors of acute rejection after lung transplantation.Ann Thorac Surg. 2011; 91: 1754-1762Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar The generation of antibodies against allogeneic antigen leads to repeated episodes of ACR, which increases the risk of irreversible graft dysfunction. Lymphocytic bronchitis and pulmonary infections are also likely to be precursors of BOS.13Bando K. Paradis I.L. Similo S. et al.Obliterative bronchiolitis after lung and heart-lung transplantation. An analysis of risk factors and management.J Thorac Cardiovasc Surg. 1995; 110: 4-13Abstract Full Text PDF PubMed Scopus (391) Google Scholar The non-alloimmune factors implicated in graft injury include primary graft dysfunction and result mainly from ischemia-reperfusion injury, with gastroesophageal reflux, subsequent microaspiration and infection also implicated.12Mangi A.A. Mason D.P. Nowicki E.R. et al.Predictors of acute rejection after lung transplantation.Ann Thorac Surg. 2011; 91: 1754-1762Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar, 14Nicod L.P. Mechanisms of airway obliteration after lung transplantation.Proc Am Thorac Soc. 2006; 3: 444-449Crossref PubMed Scopus (86) Google Scholar Epithelial-to-mesenchymal transition (EMT) is characterized by loss of cell-to-cell contact and cytoskeleton remodeling in epithelial cells leading to transformation into fibroblast-like cells expressing mesenchymal markers. These epithelial cells pass through various stages before acquiring mesenchymal properties. This process is characterized by reduced expression of epithelial cell markers such as cytokeratins, E-cadherin and zonula occludins-1, which are involved in maintaining cell-cell contact and structural integrity. Furthermore, due to loss of cell-adhesion proteins, epithelial cells lose their normal cellular organization, leading to increased expression of fibroblastic proteins such as vimentin and fibronectin.15Ward C. Forrest I.A. Murphy D.M. et al.Phenotype of airway epithelial cells suggests epithelial to mesenchymal cell transition in clinically stable lung transplant recipients.Thorax. 2005; 60: 865-871Crossref PubMed Scopus (109) Google Scholar, 16Huyard F. Yzydorczyk C. Castro M.M. et al.Remodeling of aorta extracellular matrix as a result of transient high oxygen exposure in newborn rats: implication for arterial rigidity and hypertension risk.PLoS One. 2014; 9: e92287Crossref PubMed Scopus (23) Google Scholar The differential expression of epithelial and mesenchymal proteins can therefore be used to track the EMT. For instance, expression of the fibroblast-specific protein S100-A4 is an early marker of EMT in mesenchymal cells.17Sato M. Shames D.S. Hasegawa Y. Emerging evidence of epithelial-to-mesenchymal transition in lung carcinogenesis.Respirology. 2012; 17: 1048-1059Crossref PubMed Scopus (78) Google Scholar, 18Zhao H. Chan-Li Y. Collins S.L. et al.Pulmonary delivery of docosahexaenoic acid mitigates bleomycin-induced pulmonary fibrosis.BMC Pulm Med. 2014; 14: 64Crossref PubMed Scopus (26) Google Scholar Matrix metalloproteinases (MMPs) are another set of markers that have profound implications in EMT. MMPs consist of 24 zinc-dependent endopeptidases that are released in response to allograft injury and environmental factors. These enzymes degrade the basement membrane-causing damage, differentiation and translocation of epithelial cells, thereby promoting EMT.19Greenlee K.J. Werb Z. Kheradmand F. Matrix metalloproteinases in lung: multiple, multifarious, and multifaceted.Physiol Rev. 2007; 87: 69-98Crossref PubMed Scopus (350) Google Scholar, 20Egger C. Gérard C. Vidotto N. et al.Lung volume quantified by MRI reflects extracellular-matrix deposition and altered pulmonary function in bleomycin models of fibrosis: effects of SOM230.Am J Physiol Lung Cell Mol Physiol. 2014; 306: L1064-L1077Crossref PubMed Scopus (32) Google Scholar, 21Jugdutt B.I. Ventricular remodeling after infarction and the extracellular collagen matrix: when is enough enough?.Circulation. 2003; 108: 1395-1403Crossref PubMed Scopus (530) Google Scholar Current research has shown that MMP-2 and MMP-9 activate latent transforming growth factor-beta (TGF-β) by proteolytic cleavage, thus promoting angiogenesis. MMPs have also been shown to induce EMT in primary bronchial epithelial cells (PBECs) and in a lung adenocarcinoma (A549) cell line.22Camara J. Jarai G. Epithelial-mesenchymal transition in primary human bronchial epithelial cells is Smad-dependent and enhanced by fibronectin and TNF-alpha.Fibrogen Tissue Repair. 2010; 3: 2Crossref PubMed Scopus (152) Google Scholar, 23Van Linthout S. Miteva K. Tschope C. Crosstalk between fibroblasts and inflammatory cells.Cardiovasc Res. 2014; 102: 258-269Crossref PubMed Scopus (325) Google Scholar, 24Yu Q. Stamenkovic I. Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis.Genes Dev. 2000; 14: 163-176Crossref PubMed Google Scholar TGF-β1 is a potent inducer of EMT, and the Smad signaling pathway components govern its downstream effects. Once activated, the Smad complex translocates into the nucleus and transcribes genes involved in fibrosis. TGF-β1 has been used to induce EMT in alveolar epithelial cells; these cells exhibit extreme plasticity that may serve as a source of fibroblasts in lung fibrosis.25Vancheri C. Failla M. Crimi N. et al.Idiopathic pulmonary fibrosis: a disease with similarities and links to cancer biology.Eur Respir J. 2010; 35: 496-504Crossref PubMed Scopus (335) Google Scholar, 26Willis BC, Borok Z. TGF-β-induced EMT: mechanisms and implications for fibrotic lung disease. Am J Physiol Lung Cell Mol Physiol. 2007;293:L525-34.Google Scholar Studies by our group have shown that markers associated with cell migration and EMT (Figure 2) are upregulated in TGF-β1-stimulated A549 and BEAS-2B cells.27Ladak SS, Ali S, Ward C. The potential role of miRNA-200b in the development of Bronchiolitis obliterans syndrome. In Immunology (Vol. 143, pp. 171-171), New Jersey, Wiley-Blackwell; 2014.Google Scholar These findings and early EMT studies demonstrate the role of EMT markers in lung fibrosis. The role of microRNAs (miRNAs) has been well documented in various pathologic processes and they are of likely importance in the progression and maintenance of lung disease. miRNAs are small, non-coding RNAs (19 to 22 nucleotides in length) that are highly conserved among species and modulate the expression of several genes at the transcriptional level by controlling various pathways.28Lino C. Christian L. Kaminski N. et al.Micromanaging microRNAs: using murine models to study microRNAs in lung fibrosis.Drug Discov Today Dis Mod. 2013; 10: e145-e151Crossref PubMed Scopus (15) Google Scholar miRNAs are transcribed in the nucleus from introns or exons by RNA polymerase II to generate long primary transcripts that are terminally cleaved by Drosha (RNase III enzyme) into a hairpin-like structure called pre-miRNA. These are subsequently transported into cytoplasm by exportin-5 protein. At that point, a dicer molecule cleaves pre-miRNA to generate double-stranded mature miRNA duplexes. One of the strands of the mature miRNA binds to the Argonaut family protein Ago2, is incorporated into the RNA inducing silencing complex, and binds to the 3’ UTR of the target mRNA. If miRNA aligns correctly to the target strand, then translation is repressed; alternatively, if the binding is partially complementary, then it leads to degradation of the target mRNA strand.29Wang Q.Z. Xu W. Habib N. et al.Potential uses of microRNA in lung cancer diagnosis, prognosis, and therapy.Curr Cancer Drug Targets. 2009; 9: 572-594Crossref PubMed Scopus (112) Google Scholar Assaying miRNAs can be useful not only for identification of novel miRNA candidates but also for studying miRNA–mRNA and miRNA–protein interactions.30Pritchard C.C. Cheng H.H. Tewari M. MicroRNA profiling: approaches and considerations.Nat Rev Genet. 2012; 13: 358-369Crossref PubMed Scopus (1250) Google Scholar Computational tools allow identification of potential mRNA targets by matching the complementarity between the seed region (2 to 8 bases) of the miRNA and the 3’ untranslated region of an mRNA.31Lemons D. Maurya M.R. Subramaniam S. et al.Developing microRNA screening as a functional genomics tool for disease research.Front Physiol. 2013; 4: 223Crossref PubMed Scopus (17) Google Scholar The TargetScan tool calculates a score after finding a perfect complement match to the seed region. Based on site type, it also takes into consideration other aspects of seed matching, such as A-U enrichment.32Lewis B.P. Shih I.H. Jones-Rhoades M.W. et al.Prediction of mammalian microRNA targets.Cell. 2003; 115: 787-798Abstract Full Text Full Text PDF PubMed Scopus (4223) Google Scholar MiRanda uses a complementarity score to select the miRNA-mRNA duplexes.33Enright A.J. John B. Gaul U. et al.MicroRNA targets in Drosophila.Genome Biol. 2003; 5: R1Crossref PubMed Google Scholar The PicTar algorithm locates all perfect seed (~7-seed match) or imperfect seed regions in 3’ UTR and predicts the score for each match.34Krek A. Grun D. Poy MN et al.Combinatorial microRNA target predictions.Nat Genet. 2005; 37: 495-500Crossref PubMed Scopus (3897) Google Scholar Each prediction tool uses a different rule of miRNA targeting and therefore produces a different list of predicted mRNA targets. As a result, the targets acquired may not be genuine and the definitive targets can be missed. Therefore, more than one tool is required for experimental data and only the overlapping results need be considered to conclude whether a miRNA-mRNA interaction is reliable.35Shkumatava A. Stark A. Sive H. et al.Coherent but overlapping expression of microRNAs and their targets during vertebrate development.Genes Dev. 2009; 23: 466-481Crossref PubMed Scopus (91) Google Scholar, 36Thomson D.W. Bracken C.P. Goodall G.J. Experimental strategies for microRNA target identification.Nucleic Acids Res. 2011; 39: 6845-6853Crossref PubMed Scopus (446) Google Scholar A common approach to study the expression of miRNA and miRNA-mRNA interaction relies on well-established techniques, such as quantitative real-time polymerase chain reaction (qRT-PCR), Western blot and luciferase reporter assays. qRT-PCR is employed to study the expression of miRNA and its downstream mRNA targets at the RNA level. Pre-designed qRT-PCR plates allow screening of known miRNAs in various samples; however, this technique is not suitable for screening novel miRNAs.37Maltby S. Plank M. Ptaschinski C. et al.MicroRNA function in mast cell biology: protocols to characterize and modulate microRNA expression.Methods Mol Biol. 2015; 1220: 287-304Crossref PubMed Scopus (10) Google Scholar Western blot studies allow studying the downstream effects of differential miRNA expression at the protein level. The direct effects of miRNA are demonstrated using luciferase reporter assays. The 3’ UTR region of the miRNA target gene is incorporated into the luciferase construct. Altered luciferase-3’ UTR due to manipulation of a miRNA indicates a direct link between the target and miRNA.38Kuhn D.E. Martin M.M. Feldman D.S. et al.Experimental validation of miRNA targets.Methods. 2008; 44: 47-54Crossref PubMed Scopus (294) Google Scholar Hybridization-based techniques (NanoString Technologies, Seattle, WA) have been widely used to screen >800 miRNAs and thus allow identification of novel miRNAs. The NanoString nCounter human miRNA v2 assay has also been used to examine expression of miRNA signatures in formalin-fixed, paraffin-embedded samples obtained from patients post-prostatectomy. The nCounter system was also used to study miRNA expression in primary human small airway epithelial cells (HSAEpCs) that were subjected to 12 hours of oscillating pressure and/or tumor necrosis factor-alpha (TNF-α) treatment. This experiment was conducted to determine changes in miRNA expression after mechanical ventilation trauma and its role in regulating inflammation. miRNA profiling results suggested a significant (p < 0.05) increase in miR-146a expression in HSAEpCs exposed to oscillating pressure. This was further confirmed by qRT-PCR. miR-146a target studies were also performed using luciferase reporter assay that confirmed IRAK1 and TRAF6 as its direct targets. Furthermore, the study elucidated the role of these targets in maintaining cytokine secretion in lung epithelia. The study further demonstrated the use of various techniques to screen, select and identify miRNAs and miRNA targets involved in lung dysfunction.39Huang Y. Crawford M. Higuita-Castro N. et al.miR-146a regulates mechanotransduction and pressure-induced inflammation in small airway epithelium.FASEB J. 2012; 26: 3351-3364Crossref PubMed Scopus (19) Google Scholar Identification of unique signatures and their differential expression may help in distinguishing various outcomes, such as early graft dysfunction associated with rejection, and others without rejection history. Because miRNAs are relatively stable, they are well preserved in a range of sample types, including formalin-fixed tissues, urine and serum or blood plasma. Therefore, studying the differential expression of miRNA in various samples is achievable.40Montano M. MicroRNAs: miRRORS of health and disease.Transl Res. 2011; 157: 157-162Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar, 41Zhang W. Zhou T. Ma S.F. et al.MicroRNAs implicated in dysregulation of gene expression following human lung transplantation.Transl Respir Med. 2013; 1Google Scholar miRNA profiling has been conducted to investigate the functions of miRNAs in different disease and normal human tissues. One recent study showed expression of 345 miRNAs in 40 normal human tissues that were universally expressed and several others that were exclusively expressed in specific tissues. Human tissue samples were hierarchically clustered based on anatomic position and functions using an miRNA expression profile. Results suggest that miRNAs and their host genes had coordinated expression patterns in these tissues. The data also present an overall view of miRNA distribution in various tissues in relation to their chromosomal patterns.42Liang Y. Ridzon D. Wong L. et al.Characterization of microRNA expression profiles in normal human tissues.BMC Genomics. 2007; 8: 166Crossref PubMed Scopus (862) Google Scholar miRNA quantification in biofluids has emerged as a promising new approach for disease biomarker detection. It has recently been shown that disease-specific exosomes and/or extracellular vesicle (EV) signatures may be useful in differentiating between normal and disease states. EVs include exosomes (<100 nm) and microparticles (100 to 1,000 nm), wherein the former are formed and stored in the cell before being released and the latter are generated through a process called ectocytosis (cell membrane shedding).43Julich H. Willms A. Lukacs-Kornek V. et al.Extracellular vesicle profiling and their use as potential disease specific biomarker.Front Immunol. 2014; 5: 413Crossref PubMed Scopus (58) Google Scholar The development of antibodies to donor-mismatched HLA (DSA) and BOS has shown an association with 8 selectively expressed circulating miRNAs (miR-369-5p, miR-144, miR-134, miR-10a, miR-142-5p, miR-195 and miR-155) in lung recipients with BOS as compared with stable LT patients. Dysregulated expression of TGF-β–associated miRNAs, namely miR-369-5p and miR-144, in lung transplant recipients with DSA and BOS suggested their role in fibrosis driven by TGF-β signaling. Furthermore, results acquired from a cohort of DSA+ BOS− and DSA+ BOS+ lung allograft recipients indicate that the miRNA candidates identified could differentiate LT recipients susceptible to development of DSA and BOS compared to those with stable lung transplants.44Xu Z. Nayak D. Trulock E. et al.OR15 De novo development of DSA following human lung transplantation is associated with changes on circulating micro-RNA involved in T and B cell regulation and fibrogenesis.Hum Immunol. 2015; 76: 13Crossref PubMed Google Scholar In addition to the findings just described, miRNA expression profiles of mononuclear cells from stable LTs (LT, n = 10), DSA+ BOS− LTs (DSA group, n = 10) and DSA+ BOS+ LTs (BOS group, n = 10) was carried out to assess the role of anti-HLA antibodies in the development of BOS. The results suggest that development of DSA altered the expression of miRNAs affecting TGF-β and other associated signaling pathways (such as B-cell receptor) that may play an integral role in development of BOS.45Xu Z. Nayak D. Yang W. et al.Dysregulated MicroRNA expression and chronic lung allograft rejection in recipients with antibodies to donor HLA.Am J Transplant. 2015; 15: 1933-1947Crossref PubMed Scopus (38) Google Scholar miR-144 is another candidate involved in fibrosis, which is known to lead to BOS. Expression of miR-144 was examined in biopsy specimens obtained from LT recipients with and without BOS. BOS+ patients demonstrated a significant increase in miR-144 expression (4.1 ± 0.8-fold) compared with the BOS− patients. Overexpression of miR-144 resulted in a significant decrease in TGF-β–induced factor homeobox 1, which is a co-repressor of smads. Thus, miR-144 is a major biomarker of BOS.46Xu Z. Ramachandran S. Gunasekaran M. et al.MicroRNA-144 dysregulates the transforming growth factor-beta signaling cascade and contributes to the development of bronchiolitis obliterans syndrome after human lung transplantation.J Heart Lung Transplant. 2015; 34: 1154-1162Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar Fibrotic lung diseases, such as silicosis, are associated with altered miRNA expression. Genome-wide miRNA profiling in a mouse model (with silicosis) using microarray allowed identification of 17 differentially expressed miRNAs between the control and silica groups. miR-486-5p was significantly decreased in this mouse model with silicosis. This was also shown in the bleomycin-induced fibrosis mouse model and in serum of patients with silicosis and idiopathic pulmonary fibrosis. A miRNA target study elucidated SMAD2 as one of the targets of miR-486-5p. Finally, overexpression of miR-486-5p in silica mouse models decreased lung lesions, suggesting its role in inhibiting fibrosis.47Ji X. Wu B. Fan J. et al.The anti-fibrotic effects and mechanisms of microRNA-486-5p in pulmonary fibrosis.Sci Rep. 2015; 5: 14131Crossref PubMed Scopus (75) Google Scholar In addition, Dong et al reported that expression of selective transcription factors (Myc/Max and FOXM1) and miRNAs (miR-376-5p and miR-338-3p) may prevent development of lung allograft dysfunction.48Dong M. Wang X. Zhao H.L. et al.Integrated analysis of transcription factor, microRNA and LncRNA in an animal model of obliterative bronchiolitis.Int J Clin Exp Pathol. 2015; 8: 7050-7058PubMed Google Scholar Expression of selective miRNAs may determine the risk of developing inflammation and fibrosis post-transplant. For example, secreted miR-21 from injured tubular epithelial cells packaged into microvesicles was found to promote phenotypic changes. Also, exogenous miR-21 was shown to downregulate phosphatase and tensin homolog protein, enhance Akt signaling, and promote tubular phenotypic transition.49Zhou Y. Xiong M. Fang L. et al.miR-21-containing microvesicles from injured tubular epithelial cells promote tubular phenotype transition by targeting PTEN protein.Am J Pathol. 2013; 183: 1183-1196Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar Despite limited research in this area, the potential role of miRNAs as biomarkers for early diagnosis of allograft rejection may have a major impact in the field of LT in the near future (Table 2). There have been few studies related to lung allograft rejection in humans; however, work has been done to study the role of miRNAs in the post-transplantat setting of other solid organs.Table 2Differential Expression on microRNAs in Various Tissues During Acute and Chronic Allograft InjuryAllograft dysfunctionDifferentially expressed miRNAsTarget tissueAcute injury and inflammationmiR-155, miR-146b, miR-146a, miR-200a, miR-10a, miR-10b, miR-18aKidney55Anglicheau D. Sharma V.K. Ding R. et al.MicroRNA expression profiles predictive of human renal allograft status.Proc Natl Acad Sci USA. 2009; 106: 5330-5335Crossref PubMed Scopus (285) Google Scholar, 93Saikumar J. Hoffmann D. Kim T.M. et al.Expression, circulation, and excretion profile of microRNA-21, -155, and -18a following acute kidney injury.Toxicol Sci. 2012; 129: 256-267Crossref PubMed Scopus (157) Google ScholarmiR-326, miR-142-3p, miR-10a, miR-31, miR-92a, miR-155, miR-133bHeart94Van Huyen J.P. Tible M. Gay A. et al.MicroRNAs as non-invasive biomarkers of heart transplant rejection.Eur Heart J. 2014; 35: 3194-3202Crossref PubMed Scopus (152) Google Scholar, 95Wang E. Nie Y. Zhao Q. et al.Circulating miRNAs reflect early myocardial injury and recovery after heart transplantation.J Cardiothorac Surg. 2013; 8: 165Crossref PubMed Scopus (42) Google ScholarmiR-122, miR-148a, miR-192, miR-194Liver96Farid W.R. Pan Q. van der Meer A.J. et al.Hepatocyte-derived microRNAs as serum biomarkers of hepatic injury and rejection after liver transplantation.Liver Transpl. 2012; 18: 290-297Crossref PubMed Scopus (150) Google ScholarmiR-127, miR-146a, miR-181b, miR-24, miR-26a, miR-126, miR-30a/b, miR-135b, miR-346, miR-146a/bLung97Kishore A. Borucka J. Petrkova J. et al.Novel insights into miRNA in lung and heart inflammatory diseases.Mediators Inflamm. 2014; 2014: 259131Crossref PubMed Scopus (45) Google Scholar, 98Huang C. Xiao X. Chintagari N.R. et al." @default.
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• W2316985585 title "The potential role of microRNAs in lung allograft rejection" @default.
• W2316985585 cites W1411210768 @default.
• W2316985585 cites W141788105 @default.
• W2316985585 cites W1575470091 @default.
• W2316985585 cites W1669106649 @default.
• W2316985585 cites W1688135294 @default.
• W2316985585 cites W1691255546 @default.
• W2316985585 cites W1951356170 @default.
• W2316985585 cites W1954133876 @default.
• W2316985585 cites W1964668704 @default.
• W2316985585 cites W1964681893 @default.
• W2316985585 cites W1966189833 @default.
• W2316985585 cites W1968148254 @default.
• W2316985585 cites W1969721873 @default.
• W2316985585 cites W1971530636 @default.
• W2316985585 cites W1975981804 @default.
• W2316985585 cites W1978206249 @default.
• W2316985585 cites W1979207431 @default.
• W2316985585 cites W1979601962 @default.
• W2316985585 cites W1982738547 @default.
• W2316985585 cites W1985571291 @default.
• W2316985585 cites W1986782449 @default.
• W2316985585 cites W1987864571 @default.
• W2316985585 cites W1989277040 @default.
• W2316985585 cites W1990061381 @default.
• W2316985585 cites W1992918760 @default.
• W2316985585 cites W1994636867 @default.
• W2316985585 cites W1998630181 @default.
• W2316985585 cites W2001020067 @default.
• W2316985585 cites W2002916448 @default.
• W2316985585 cites W2007191609 @default.
• W2316985585 cites W2012011968 @default.
• W2316985585 cites W2014869583 @default.
• W2316985585 cites W2018733331 @default.
• W2316985585 cites W2019806278 @default.
• W2316985585 cites W2023289452 @default.
• W2316985585 cites W2026051181 @default.
• W2316985585 cites W2026570544 @default.
• W2316985585 cites W2030712838 @default.
• W2316985585 cites W2031014255 @default.
• W2316985585 cites W2040868568 @default.
• W2316985585 cites W2043751765 @default.
• W2316985585 cites W2044967196 @default.
• W2316985585 cites W2046357497 @default.
• W2316985585 cites W2050442471 @default.
• W2316985585 cites W2050869737 @default.
• W2316985585 cites W2051931080 @default.
• W2316985585 cites W2062739618 @default.
• W2316985585 cites W2067574290 @default.
• W2316985585 cites W2071608379 @default.
• W2316985585 cites W2071925659 @default.
• W2316985585 cites W2072378401 @default.
• W2316985585 cites W2076449784 @default.
• W2316985585 cites W2082519777 @default.
• W2316985585 cites W2085520541 @default.
• W2316985585 cites W2091096046 @default.
• W2316985585 cites W2091205606 @default.
• W2316985585 cites W2092693006 @default.
• W2316985585 cites W2096093641 @default.
• W2316985585 cites W2102627944 @default.
• W2316985585 cites W2103177465 @default.
• W2316985585 cites W2103723163 @default.
• W2316985585 cites W2105679485 @default.
• W2316985585 cites W2114181581 @default.
• W2316985585 cites W2114970103 @default.
• W2316985585 cites W2118105142 @default.
• W2316985585 cites W2120169383 @default.
• W2316985585 cites W2120456037 @default.
• W2316985585 cites W2130089581 @default.
• W2316985585 cites W2130485791 @default.
• W2316985585 cites W2135508408 @default.
• W2316985585 cites W2136059996 @default.
• W2316985585 cites W2136418621 @default.
• W2316985585 cites W2137782468 @default.
• W2316985585 cites W2140477106 @default.
• W2316985585 cites W2141023213 @default.
• W2316985585 cites W2143760046 @default.
• W2316985585 cites W2144399925 @default.
• W2316985585 cites W2145302333 @default.
• W2316985585 cites W2145646761 @default.
• W2316985585 cites W2146518187 @default.
• W2316985585 cites W2147281325 @default.
• W2316985585 cites W2147575530 @default.
• W2316985585 cites W2149748804 @default.
• W2316985585 cites W2154086186 @default.
• W2316985585 cites W2158227546 @default.
• W2316985585 cites W2159864284 @default.
• W2316985585 cites W2162313829 @default.
• W2316985585 cites W2162877470 @default.
• W2316985585 cites W2163199119 @default.
• W2316985585 cites W2164428603 @default.

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