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• W2093148727 abstract "Inflammatory cell infiltration and fibrin deposition play important roles in the development of crescentic glomerulonephritis (GN). In particular, activation of coagulation is an indispensable factor in crescent formation. However, the mechanisms underlying the pathogenesis of crescent formation have not been completely elucidated. We identified the growth factor midkine (MK) as a novel key molecule in the progression of crescentic GN induced by anti–glomerular basement membrane antibody. Despite the lack of significant differences in autologous and heterologous reactions, MK-deficient (Mdk−/−) mice unexpectedly showed a greater number of necrotizing glomerular injuries than wild-type (Mdk+/+) mice. Likewise, more tubulointerstitial damage was observed in Mdk−/− mice, and this damage positively correlated with glomerular injury. Plasminogen activator inhibitor (PAI)-1 was strongly induced in the injured glomerulus of Mdk−/− mice, particularly in crescents and endothelial cells. This enhanced PAI-1 production was associated with an increase in inflammatory cell infiltration and matrix deposition in the glomerulus and the interstitium of Mdk−/− mice. In line with these in vivo data, primary cultured endothelial cells derived from Mdk−/− mice exhibited higher PAI-1 mRNA expression on fibrin challenge and less fibrinolysis than Mdk+/+ mice. In contrast, the expression of plasminogen activators was not affected. Our combined data suggest that MK leads to a blockade of PAI-1, which is closely associated with the suppression of crescentic GN. Inflammatory cell infiltration and fibrin deposition play important roles in the development of crescentic glomerulonephritis (GN). In particular, activation of coagulation is an indispensable factor in crescent formation. However, the mechanisms underlying the pathogenesis of crescent formation have not been completely elucidated. We identified the growth factor midkine (MK) as a novel key molecule in the progression of crescentic GN induced by anti–glomerular basement membrane antibody. Despite the lack of significant differences in autologous and heterologous reactions, MK-deficient (Mdk−/−) mice unexpectedly showed a greater number of necrotizing glomerular injuries than wild-type (Mdk+/+) mice. Likewise, more tubulointerstitial damage was observed in Mdk−/− mice, and this damage positively correlated with glomerular injury. Plasminogen activator inhibitor (PAI)-1 was strongly induced in the injured glomerulus of Mdk−/− mice, particularly in crescents and endothelial cells. This enhanced PAI-1 production was associated with an increase in inflammatory cell infiltration and matrix deposition in the glomerulus and the interstitium of Mdk−/− mice. In line with these in vivo data, primary cultured endothelial cells derived from Mdk−/− mice exhibited higher PAI-1 mRNA expression on fibrin challenge and less fibrinolysis than Mdk+/+ mice. In contrast, the expression of plasminogen activators was not affected. Our combined data suggest that MK leads to a blockade of PAI-1, which is closely associated with the suppression of crescentic GN. Crescent formation in the glomerulus develops as a result of segmental breaks of the glomerular basement membrane (GBM), often in association with fibrinoid necrosis.1Eddy A.A. Fogo A.B. Plasminogen activator inhibitor-1 in chronic kidney disease: evidence and mechanisms of action.J Am Soc Nephrol. 2006; 17: 2999-3012Crossref PubMed Scopus (192) Google Scholar This component includes fibrin deposition, infiltration of inflammatory cells, and the extracellular matrix accumulation. Of these components, fibrin deposition by itself not only interrupts glomerular blood flow, leading to irreversible ischemia and glomerular obsolescence, but also promotes the infiltration of inflammatory cells and the proliferation of epithelial cells in Bowman’s space.2Hertig A. Rondeau E. Role of the coagulation/fibrinolysis system in fibrin-associated glomerular injury.J Am Soc Nephrol. 2004; 15: 844-853Crossref PubMed Scopus (66) Google Scholar The recruitment of macrophages and neutrophils, which is triggered by inflammatory mediators such as fibrin, oxidative stress, and various chemokines, further leads to the activation of coagulation during crescentic glomerulonephritis (GN) and to thrombotic microangiopathy that is accompanied by severe endothelial dysfunction.1Eddy A.A. Fogo A.B. Plasminogen activator inhibitor-1 in chronic kidney disease: evidence and mechanisms of action.J Am Soc Nephrol. 2006; 17: 2999-3012Crossref PubMed Scopus (192) Google Scholar It is therefore critical to break the vicious cycle of these processes to improve the mortality associated with aggressive kidney diseases. The glycoprotein plasminogen activator inhibitor (PAI)-1, which is a serine protease inhibitor, is the major physiologic inhibitor of important plasminogen activators, such as tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA).3Ha H. Oh E.Y. Lee H.B. The role of plasminogen activator inhibitor 1 in renal and cardiovascular diseases.Nat Rev Nephrol. 2009; 5: 203-211Crossref PubMed Scopus (118) Google Scholar Plasma and tissue concentrations of PAI-1 are extremely low under physiologic conditions but increase in pathologic states. The roles of PAI-I are diverse, ranging from the development of thrombotic disorders to involvement in ischemic diseases, fibrotic disorders, metabolic syndrome, diabetes mellitus, and cancer.1Eddy A.A. Fogo A.B. Plasminogen activator inhibitor-1 in chronic kidney disease: evidence and mechanisms of action.J Am Soc Nephrol. 2006; 17: 2999-3012Crossref PubMed Scopus (192) Google Scholar, 3Ha H. Oh E.Y. Lee H.B. The role of plasminogen activator inhibitor 1 in renal and cardiovascular diseases.Nat Rev Nephrol. 2009; 5: 203-211Crossref PubMed Scopus (118) Google Scholar, 4Roelofs J.J. Teske G.J. Bonta P.I. de Vries C.J. Meijers J.C. Weening J.J. van der Poll T. Florquin S. Plasminogen activator inhibitor-1 regulates neutrophil influx during acute pyelonephritis.Kidney Int. 2009; 75: 52-59Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar Many elegant studies suggest that up-regulation of PAI-1 in response to various stimuli, including high ambient glucose exposure,5Lee E.A. Seo J.Y. Jiang Z. Yu M.R. Kwon M.K. Ha H. Lee H.B. Reactive oxygen species mediate high glucose-induced plasminogen activator inhibitor-1 up-regulation in mesangial cells and in diabetic kidney.Kidney Int. 2005; 67: 1762-1771Abstract Full Text Full Text PDF PubMed Scopus (110) Google Scholar transforming growth factor (TGF)-β,6Jiang Z. Seo J.Y. Ha H. Lee E.A. Kim Y.S. Han D.C. Uh S.T. Park C.S. Lee H.B. Reactive oxygen species mediate TGF-beta1-induced plasminogen activator inhibitor-1 upregulation in mesangial cells.Biochem Biophys Res Commun. 2003; 309: 961-966Crossref PubMed Scopus (100) Google Scholar oxidative stress,7Liao H. Hyman M.C. Lawrence D.A. Pinsky D.J. Molecular regulation of the PAI-1 gene by hypoxia: contributions of Egr-1, HIF-1alpha, and C/EBPalpha.FASEB J. 2007; 21: 935-949Crossref PubMed Scopus (98) Google Scholar and angiotensin II,8Yoshimoto T. Fukai N. Sato R. Sugiyama T. Ozawa N. Shichiri M. Hirata Y. Antioxidant effect of adrenomedullin on angiotensin II-induced reactive oxygen species generation in vascular smooth muscle cells.Endocrinology. 2004; 145: 3331-3337Crossref PubMed Scopus (73) Google Scholar, 9Yoshimoto T. Gochou N. Fukai N. Sugiyama T. Shichiri M. Hirata Y. Adrenomedullin inhibits angiotensin II-induced oxidative stress and gene expression in rat endothelial cells.Hypertens Res. 2005; 28: 165-172Crossref PubMed Scopus (57) Google Scholar promotes interstitial macrophage recruitment and exerts direct cellular effects through binding to the uPA receptor. Indeed, PAI-1 deficiency reduces the severity of anti-GBM–induced nephritis.10Kitching A.R. Kong Y.Z. Huang X.R. Davenport P. Edgtton K.L. Carmeliet P. Holdsworth S.R. Tipping P.G. Plasminogen activator inhibitor-1 is a significant determinant of renal injury in experimental crescentic glomerulonephritis.J Am Soc Nephrol. 2003; 14: 1487-1495Crossref PubMed Scopus (75) Google Scholar An understanding of the PAI-1–mediated signaling pathways involved in these processes might aid in the development of novel therapeutic strategies for rapid progressive GN. Midkine (MK; alias Mdk) is a multifunctional, heparin-binding growth factor with major biological roles, such as neuronal survival and differentiation, cancer development, and inflammation.11Kadomatsu K. Muramatsu T. Midkine and pleiotrophin in neural development and cancer.Cancer Lett. 2004; 204: 127-143Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar The neuronal cytoprotective effects of MK have been demonstrated in various in vivo models, including retinal degeneration induced by constant light exposure,12Unoki K. Ohba N. Arimura H. Muramatsu H. Muramatsu T. Rescue of photoreceptors from the damaging effects of constant light by midkine, a retinoic acid-responsive gene product.Invest Ophthalmol Vis Sci. 1994; 35: 4063-4068PubMed Google Scholar cerebral infarction,13Yoshida Y. Goto M. Tsutsui J. Ozawa M. Sato E. Osame M. Muramatsu T. Midkine is present in the early stage of cerebral infarct.Brain Res Dev Brain Res. 1995; 85: 25-30Crossref PubMed Scopus (94) Google Scholar and ischemia-induced neuronal death.14Yoshida Y. Ikematsu S. Moritoyo T. Goto M. Tsutsui J. Sakuma S. Osame M. Muramatsu T. Intraventricular administration of the neurotrophic factor midkine ameliorates hippocampal delayed neuronal death following transient forebrain ischemia in gerbils.Brain Res. 2001; 894: 46-55Crossref PubMed Scopus (48) Google Scholar, 15Takada J. Ooboshi H. Ago T. Kitazono T. Yao H. Kadomatsu K. Muramatsu T. Ibayashi S. Iida M. Postischemic gene transfer of midkine, a neurotrophic factor, protects against focal brain ischemia.Gene Ther. 2005; 12: 487-493Crossref PubMed Scopus (38) Google Scholar In addition, MK regulates hypertension in kidney-lung interactions through activation of the renin-angiotensin system, which eventually leads to progressive renal failure with elevated angiotensin II.16Hobo A. Yuzawa Y. Kosugi T. Kato N. Asai N. Sato W. Maruyama S. Ito Y. Kobori H. Ikematsu S. Nishiyama A. Matsuo S. Kadomatsu K. The growth factor midkine regulates the renin-angiotensin system in mice.J Clin Invest. 2009; 119: 1616-1625Crossref PubMed Scopus (76) Google Scholar MK also exacerbates inflammation-related diseases, as revealed by in vivo models of diseases such as rheumatoid arthritis,17Maruyama K. Muramatsu H. Ishiguro N. Muramatsu T. Midkine, a heparin-binding growth factor, is fundamentally involved in the pathogenesis of rheumatoid arthritis.Arthritis Rheum. 2004; 50: 1420-1429Crossref PubMed Scopus (89) Google Scholar arterial restenosis,18Horiba M. Kadomatsu K. Nakamura E. Muramatsu H. Ikematsu S. Sakuma S. Hayashi K. Yuzawa Y. Matsuo S. Kuzuya M. Kaname T. Hirai M. Saito H. Muramatsu T. Neointima formation in a restenosis model is suppressed in midkine-deficient mice.J Clin Invest. 2000; 105: 489-495Crossref PubMed Scopus (173) Google Scholar ischemic reperfusion–induced renal injury,19Sato W. Kadomatsu K. Yuzawa Y. Muramatsu H. Hotta N. Matsuo S. Muramatsu T. Midkine is involved in neutrophil infiltration into the tubulointerstitium in ischemic renal injury.J Immunol. 2001; 167: 3463-3469Crossref PubMed Scopus (163) Google Scholar diabetic nephropathy,20Kosugi T. Yuzawa Y. Sato W. Arata-Kawai H. Suzuki N. Kato N. Matsuo S. Kadomatsu K. Midkine is involved in tubulointerstitial inflammation associated with diabetic nephropathy.Lab Invest. 2007; 87: 903-913Crossref PubMed Scopus (71) Google Scholar, 21Kosugi T. Yuzawa Y. Sato W. Kawai H. Matsuo S. Takei Y. Muramatsu T. Kadomatsu K. Growth factor midkine is involved in the pathogenesis of diabetic nephropathy.Am J Pathol. 2006; 168: 9-19Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar and postinfectious GN.22Kato K. Kosugi T. Sato W. Arata-Kawai H. Ozaki T. Tsuboi N. Ito I. Tawada H. Yuzawa Y. Matsuo S. Kadomatsu K. Maruyama S. Growth factor midkine is involved in the pathogenesis of renal injury induced by protein overload containing endotoxin.Clin Exp Nephrol. 2011; 15: 346-354Crossref PubMed Scopus (13) Google Scholar An inflammatory microenvironment induces MK, which in turn, induces macrophage recruitment both directly and indirectly through activation of monocyte chemoattractant protein (MCP)-1. The molecular mechanisms that induce PAI-1 under physiologic and pathologic conditions have been extensively studied. However, to date, systems that inhibit PAI-1 induction remain unknown. It is known that MK enhances fibrinolytic activity through the suppression of PAI-1 in vascular endothelial cells.23Kojima S. Soga W. Hagiwara H. Shimonaka M. Saito Y. Inada Y. Visible fibrinolysis by endothelial cells: effect of vitamins and sterols.Biosci Rep. 1986; 6: 1029-1033Crossref PubMed Scopus (13) Google Scholar, 24Kojima S. Muramatsu H. Amanuma H. Muramatsu T. Midkine enhances fibrinolytic activity of bovine endothelial cells.J Biol Chem. 1995; 270: 9590-9596Crossref PubMed Scopus (132) Google Scholar In the present study, we uncovered an unexpected and beneficial role of MK in crescentic GN by analysis of accelerated Masugi nephritis in mice. Mice deficient in the MK gene (Mdk) were generated as described previously.25Nakamura E. Kadomatsu K. Yuasa S. Muramatsu H. Mamiya T. Nabeshima T. Fan Q.W. Ishiguro K. Igakura T. Matsubara S. Kaname T. Horiba M. Saito H. Muramatsu T. Disruption of the midkine gene (Mdk) resulted in altered expression of a calcium binding protein in the hippocampus of infant mice and their abnormal behaviour.Genes Cells. 1998; 3: 811-822Crossref PubMed Scopus (120) Google Scholar After backcrossing of Mdk+/− mice for 14 generations with 129/SV mice, Mdk+/− mice were matched with each other to generate Mdk+/+ and Mdk−/− mice, which were used in this study. Experiments were performed on 8- to 12-week-old male Mdk+/+ or Mdk−/− mice weighing 20 to 30 g The mice were housed under controlled environmental conditions and maintained with standard food and water. A previously characterized model of accelerated Masugi nephritis in mice was used.26Unanue E.R. Lee S. Dixon F.J. Feldman J.D. Experimental glomerulonephritis. VII The absence of an autoimmune antikidney response in nephrotoxic serum nephritis.J Exp Med. 1965; 122: 565-578Crossref PubMed Scopus (14) Google Scholar, 27Unanue E.R. Dixon F.J. Experimental glomerulonephritis, V: studies on the interaction of nephrotoxic antibodies with tissue of the rat.J Exp Med. 1965; 121: 697-714Crossref PubMed Scopus (72) Google Scholar, 28Unanue E.R. Dixon F.J. Experimental glomerulonephritis, VI: the autologous phase of nephrotoxic serum nephritis.J Exp Med. 1965; 121: 715-725Crossref PubMed Scopus (59) Google Scholar In brief, Mdk+/+ and Mdk−/− mice (n = 7 in each group) that were sedated by general anesthesia underwent a right subcapsular nephrectomy. As described in Figure 1A, mice were preimmunized subcutaneously with 180 μg of rabbit IgG (Pierce, Rockford, IL) in Freund’s adjuvant-complete (Sigma-Aldrich, St. Louis, MO) and 7 days later were treated intravenously with 20 μL of rabbit anti-mouse GBM antibody (a gift from Prof. Yoshio Suzuki and Tadashi Nagamatsu, Meijo University). Mice were sacrificed at 3 and 7 days after injection of the anti-GBM antibody. The kidneys were removed for histologic and biochemical analysis. Blood samples were collected on each day of sacrifice. Blood urea nitrogen (BUN) and urinary albumin were measured as described previously.16Hobo A. Yuzawa Y. Kosugi T. Kato N. Asai N. Sato W. Maruyama S. Ito Y. Kobori H. Ikematsu S. Nishiyama A. Matsuo S. Kadomatsu K. The growth factor midkine regulates the renin-angiotensin system in mice.J Clin Invest. 2009; 119: 1616-1625Crossref PubMed Scopus (76) Google Scholar, 22Kato K. Kosugi T. Sato W. Arata-Kawai H. Ozaki T. Tsuboi N. Ito I. Tawada H. Yuzawa Y. Matsuo S. Kadomatsu K. Maruyama S. Growth factor midkine is involved in the pathogenesis of renal injury induced by protein overload containing endotoxin.Clin Exp Nephrol. 2011; 15: 346-354Crossref PubMed Scopus (13) Google Scholar All of the animal experiments were performed in accordance with the animal experimentation guidelines of Nagoya University School of Medicine. A kidney tissue sample was embedded in OCT compound and frozen in liquid nitrogen for immunofluorescence staining. Sections (4-μm thick) were cut using a cryostat and then fixed in acetone. The cryosections were stained with fluorescein isothiocyanate (FITC) goat anti-rabbit IgG antibody (Cappel, West Chester, PA), FITC-rabbit anti-mouse IgG antibody (Zymed, San Francisco, CA), and FITC-goat anti-mouse C3 antibody (Cappel). The cryosections were also stained with a monoclonal rat anti-mouse neutrophil marker 7/4 (Cedarlane, Ontario, Canada), followed by its detection with FITC-goat anti-rat IgG (Cedarlane). Leukocytes positive for the 7/4 marker were counted by examination of sections of 20 glomeruli per subject. The glomeruli analyzed were cut at their vascular pole and were analyzed in a blinded manner by two independent observers.22Kato K. Kosugi T. Sato W. Arata-Kawai H. Ozaki T. Tsuboi N. Ito I. Tawada H. Yuzawa Y. Matsuo S. Kadomatsu K. Maruyama S. Growth factor midkine is involved in the pathogenesis of renal injury induced by protein overload containing endotoxin.Clin Exp Nephrol. 2011; 15: 346-354Crossref PubMed Scopus (13) Google Scholar Negative controls were performed by replacement of the primary antibody with species-matched antibody. The removed kidneys were fixed in 4% paraformaldehyde, embedded in paraffin, and then cut into 4-μm sections. The sections were stained with PAS for evaluation of the development of severe glomerular damage and tubulointerstitial injury. The number of injured glomeruli per total glomeruli of each subject was calculated and expressed as a percentage.29Horio T. Development and fate of crescentic and granulomatous lesions in rat Masugi nephritis.Pathol Int. 2001; 51: 72-81Crossref PubMed Scopus (8) Google Scholar Glomerular abnormalities included crescent formation, which was defined as two or more layers of cells visible in Bowman’s space, and severe necrosis that affected >50% of the glomerular tuft.30Steinmetz O.M. Summers S.A. Gan P.Y. Semple T. Holdsworth S.R. Kitching A.R. The Th17-defining transcription factor RORgammat promotes glomerulonephritis.J Am Soc Nephrol. 2011; 22: 472-483Crossref PubMed Scopus (72) Google Scholar The percentage of atrophic tubules (tubular dilation, detachment of tubular epithelial cells, condensation of tubular nuclei, and cast formation) was assessed by scoring 800 renal cortical tubules in randomly selected fields for each subject.20Kosugi T. Yuzawa Y. Sato W. Arata-Kawai H. Suzuki N. Kato N. Matsuo S. Kadomatsu K. Midkine is involved in tubulointerstitial inflammation associated with diabetic nephropathy.Lab Invest. 2007; 87: 903-913Crossref PubMed Scopus (71) Google Scholar All scoring was performed on blinded slides by two independent observers. The sections embedded in paraffin were stained with phosphotungstic acid hematoxylin (PTAH) reagent and were examined for the development of fibrin formation. They were stained with polyclonal sheep anti-human fibrinogen antibody (Acris Antibodies GmbH, Herford, Germany), followed by biotinylated rabbit anti-sheep IgG antibody (Vector, Burlingame, CA) and avidin-biotinylated horseradish peroxidase complex (Vectastain Elite ABC kit, Vector, Burlingame, CA). The extent of fibrin deposition for each subject, which was indicated as PTAH- or fibrinogen-positive areas, was assessed as a percentage of the total glomerular area by examination of all glomeruli that were cut at their vascular pole in the section analyzed. Blood components were excluded in PTAH staining. The glomerular area was also stained along the outline of the Bowman’s capsule, and these areas were measured using the MetaMorph 6.3 image analysis computer program (Universal Imaging Co., West Chester, PA). Paraffin-embedded sections were stained with biotinylated monoclonal rat anti-mouse MAC2 antibody (Cedarlane), monoclonal rat anti-mouse macrophage marker F4/80 antibody (AbD Serotec, Oxford, UK), or biotinylated polyclonal rabbit anti-mouse plasminogen activator (PAI)-1 antibody (Abcam, Cambridge, UK), followed by detection using an avidin-biotinylated horseradish peroxidase complex (Vectastain Elite ABC kit, Vector, Burlingame, CA) or peroxidase-labeled goat anti-rat IgG antibody [Histofine Simple Stain Max PO (Rat), Nichirei Corp., Tokyo, Japan] as appropriate. Staining was visualized with 3,3′-diaminobenzidine (Nichirei Corp.), which produces a brown color. Negative controls involved replacement of the primary antibodies with species-matched antibodies. PAI-1–positive stained areas for each subject were measured in the cortical fields of 40 glomeruli, using the MetaMorph 6.3 image analysis computer program (Universal Imaging Co.). Monocytes-macrophages that were positive for Mac2 or F4/80 were counted by examination of randomly selected 20 glomeruli or 10 cortical fields under a microscope at ×200 magnification for each subject, in a blinded manner by two independent observers, respectively. Kidney samples were thawed over ice. A portion of each kidney was homogenized in T-PER Tissue Protein Extraction Reagent (Pierce). The homogenate was centrifuged at 10,000 × g for 5 minutes at 4°C. The supernatant was collected and used to determine total protein concentration using the bicinchoninic acid protein assay kit (Pierce). The levels of PAI-1, MCP-1, microphage inflammatory protein (MIP)-2, or keratinocyte-derived chemokine (KC) in the kidney homogenates were measured using specific enzyme-linked immunosorbent assays (ELISA) according to the instructions of the manufacturer (Innovative Research, Novi, MI; R&D Systems, Minneapolis, MN).31Ishimoto T. Takei Y. Yuzawa Y. Hanai K. Nagahara S. Tarumi Y. Matsuo S. Kadomatsu K. Downregulation of monocyte chemoattractant protein-1 involving short interfering RNA attenuates hapten-induced contact hypersensitivity.Mol Ther. 2008; 16: 387-395Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar The results were normalized to the total protein concentration. Mouse kidney tissues were snap-frozen in liquid nitrogen for total mRNA isolation. To perform mRNA extraction and cDNA synthesis, we used the RNeasy Mini Kit and the QuantiTect Reverse Transcriptional Kit (Qiagen, Hilden, Germany), according to the manufacturer instructions. Real-time PCR analysis was performed with an Applied Biosystems Prism 7500HT sequence detection system using TaqMan gene expression assays according to the manufacturer specifications (Applied Biosystems, Foster City, CA). TaqMan probes and primers for PAI-1 (Serpine; Mm00435860_m1), MK,16Hobo A. Yuzawa Y. Kosugi T. Kato N. Asai N. Sato W. Maruyama S. Ito Y. Kobori H. Ikematsu S. Nishiyama A. Matsuo S. Kadomatsu K. The growth factor midkine regulates the renin-angiotensin system in mice.J Clin Invest. 2009; 119: 1616-1625Crossref PubMed Scopus (76) Google Scholar MCP-1 (Ccl2; Mm00441242_m1), MIP-2 (Cxcl2; Mm00436450_m1), KC (Cxcl1; Mm04207460_m1), tPA (Plat; Mm00476931_m1), uPA (Plau; Mm00447054_m1), TGF-β (tgf-β; Mm01178820_m1), renin,16Hobo A. Yuzawa Y. Kosugi T. Kato N. Asai N. Sato W. Maruyama S. Ito Y. Kobori H. Ikematsu S. Nishiyama A. Matsuo S. Kadomatsu K. The growth factor midkine regulates the renin-angiotensin system in mice.J Clin Invest. 2009; 119: 1616-1625Crossref PubMed Scopus (76) Google Scholar angiotensinogen (AGT)16Hobo A. Yuzawa Y. Kosugi T. Kato N. Asai N. Sato W. Maruyama S. Ito Y. Kobori H. Ikematsu S. Nishiyama A. Matsuo S. Kadomatsu K. The growth factor midkine regulates the renin-angiotensin system in mice.J Clin Invest. 2009; 119: 1616-1625Crossref PubMed Scopus (76) Google Scholar and angiotensin-converting enzyme (ACE),16Hobo A. Yuzawa Y. Kosugi T. Kato N. Asai N. Sato W. Maruyama S. Ito Y. Kobori H. Ikematsu S. Nishiyama A. Matsuo S. Kadomatsu K. The growth factor midkine regulates the renin-angiotensin system in mice.J Clin Invest. 2009; 119: 1616-1625Crossref PubMed Scopus (76) Google Scholar and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (Gapdh; Mm99999915_g1) were used. Amplification data were analyzed with Applied Biosystems Sequence Detection software version 1.3.1. Formalin-fixed, paraffin-embedded (FFPE) kidney sections were mounted on poly-l-lysin–coated (Sigma-Aldrich), glass foil, polyethylene naphthalate slides for laser microdissection (Leica Microsystems, Wetzlar, Germany). After toluidine blue staining, glomeruli and tubulointerstitium were dissected using the LMD 7000 system (Leica Microsystems) and collected into each tubes filled with deparaffinization buffer (Qiagen). The extraction of total RNA was performed with the RNeasy FFPE kit (Qiagen). These samples were analyzed by real-time PCR. Serum PAI-1 level was measured by Milliplex map mouse serum adipokine kit (Millipore, Billerica, MA) following the manufacturer instructions. The data were analyzed in a Bioplex 200 system, using the Bioplex manager software version 6.0 (Bio-Rad, Hercules, CA). Endothelial cell cultures were established from the lung tissue of adult Mdk+/+ or Mdk−/− mice, from which endothelial cells were isolated by conventional sieving methods using sheep anti-rat IgG Dynal beads (Invitrogen Dynal As, Oslo, Norway) coated with anti–platelet endothelial cell adhesion molecule 1 (BD Biosciences, Bedford, MA) and anti–intercellular adhesion molecule 1 (BD Biosciences) antibodies, as previously reported.32Lim Y.C. Garcia-Cardena G. Allport J.R. Zervoglos M. Connolly A.J. Gimbrone Jr., M.A. Luscinskas F.W. Heterogeneity of endothelial cells from different organ sites in T-cell subset recruitment.Am J Pathol. 2003; 162: 1591-1601Abstract Full Text Full Text PDF PubMed Scopus (130) Google Scholar The isolated mouse lung endothelial cells (MLECs) were identified by fluorescence-activated cell sorting, using anti-CD31 (BD Biosciences) and anti-CD102 (BD Biosciences) antibodies, and were then maintained in growth medium (Dulbecco’s modified Eagle’s medium containing 20% fetal bovine serum), supplemented with endothelial cell growth stimulant (Biomedical Technologies Inc., Stoughton, MA), containing porcine heparin, nonessential amino acids, sodium pyruvate, l-glutamine, and penicillin-streptomycin (Wako Pure Chemical Industries, Ltd., Osaka, Japan). To confirm the relationship between MK and PAI-1 expression in vitro, MLECs from Mdk+/+ or Mdk−/− mice were exposed to fibrin for 72 hours as described previously.23Kojima S. Soga W. Hagiwara H. Shimonaka M. Saito Y. Inada Y. Visible fibrinolysis by endothelial cells: effect of vitamins and sterols.Biosci Rep. 1986; 6: 1029-1033Crossref PubMed Scopus (13) Google Scholar The fibrin gel was prepared using a biological tissue adhesive kit (Astellas Pharma Inc., Tokyo, Japan) according to the manufacturer instructions. Cell growth was synchronized and the culture media containing fetal bovine serum was changed every day. PAI-1, tPA, and uPA mRNA expression in cell lysates was then evaluated by real-time PCR analysis. The measurement of systolic blood pressure was performed on day 14 and day 0, before the administration of rabbit anti-GBM serum, to certify the influence of unilateral nephrectomy. Blood pressure was measured by tail cuff method.16Hobo A. Yuzawa Y. Kosugi T. Kato N. Asai N. Sato W. Maruyama S. Ito Y. Kobori H. Ikematsu S. Nishiyama A. Matsuo S. Kadomatsu K. The growth factor midkine regulates the renin-angiotensin system in mice.J Clin Invest. 2009; 119: 1616-1625Crossref PubMed Scopus (76) Google Scholar The blots of serum on the polyvinylidene difluoride membrane (GE Healthcare, Little Chalfont, Buckinghamshire, UK) were incubated with rabbit IgG (R&D Systems, Minneapolis, MN) or PBS, followed by incubation with peroxidase-conjugated goat anti-rabbit IgG antibody or rabbit anti-mouse IgG antibody (Jackson Immunoresearch Laboratories, West Grove, PA), respectively. Proteins were visualized with an enhanced chemiluminescence detection system (GE Healthcare). The intensity of each blot was measured using the MetaMorph 6.3 image analysis computer program (Universal Imaging Co.). All values are expressed as mean ± SD. Statistical analysis was performed using the unpaired, two-tailed Student’s t-test for single comparisons or analysis of variance for multiple comparisons. Post hoc least significant difference tests were performed if the initial analysis of variance was significant. P < 0.05 was considered to indicate statistically significant differences. To develop a mouse model of crescentic GN, Mdk+/+ and Mdk−/− mice underwent uninephrectomy, were preimmunized with rabbit IgG, and were then treated with rabbit anti-mouse GBM antibody (Figure 1A). No significant differences in these two genotypes were found in urinary albumin, systolic blood pressure, BUN, and pathogenic factors, such as TGF-β, PAI-1, MCP-1, renin, AGT, and ACE, before induction of accelerated Masugi nephritis (see Supplemental Figures S1 and S2). These data indicate that unilateral nephrectomy did not affect basal states of both genotypes before the induction of immune renal injury. We next evaluated the severity of the immune and inflammatory response to anti-GBM treatment in both mouse groups. In the heterologous response phase, which is affected by the injected rabbit IgG against mouse GBM, high deposition of rabbit IgG in the glomeruli was observed in both genotypes to a similar extent on day 1 (Figure 1B). Likewise, in the autologous response phase, which is a result of the reaction of mouse IgG with rabbit IgG preimmunized GBM, a similar degree of mouse IgG depositio" @default.
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• W2093148727 date "2013-02-01" @default.
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• W2093148727 title "Deficiency of Growth Factor Midkine Exacerbates Necrotizing Glomerular Injuries in Progressive Glomerulonephritis" @default.
• W2093148727 cites W1936557532 @default.
• W2093148727 cites W1972334219 @default.
• W2093148727 cites W1973138150 @default.
• W2093148727 cites W1980359098 @default.
• W2093148727 cites W1983392569 @default.
• W2093148727 cites W1984038520 @default.
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• W2093148727 cites W2000932006 @default.
• W2093148727 cites W2002584827 @default.
• W2093148727 cites W2011339992 @default.
• W2093148727 cites W2027274931 @default.
• W2093148727 cites W2037255279 @default.
• W2093148727 cites W2046796695 @default.
• W2093148727 cites W2054207249 @default.
• W2093148727 cites W2059248709 @default.
• W2093148727 cites W2068166346 @default.
• W2093148727 cites W2078657995 @default.
• W2093148727 cites W2081006617 @default.
• W2093148727 cites W2084556092 @default.
• W2093148727 cites W2092483302 @default.
• W2093148727 cites W2094242221 @default.
• W2093148727 cites W2101846172 @default.
• W2093148727 cites W2103402207 @default.
• W2093148727 cites W2116763746 @default.
• W2093148727 cites W2127216982 @default.
• W2093148727 cites W2129680188 @default.
• W2093148727 cites W2130008461 @default.
• W2093148727 cites W2139139037 @default.
• W2093148727 cites W2141797473 @default.
• W2093148727 cites W2143920612 @default.
• W2093148727 cites W2148081733 @default.
• W2093148727 cites W2157939042 @default.
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