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• W2968103410 abstract "Nasal polyposis and eye pterygium are two inflammatory diseases of the nasal mucosa and ocular surface, respectively, characterized by inflammatory cell infiltration, modifications of epithelial differentiation, tissue remodeling, and abnormal extracellular matrix accumulation. High expression of IL-6, type-I collagen, and TIMP-1 has been identified in nasal polyps and pterygium tissues in comparison with normal nasal mucosa and eye conjunctiva, respectively. Wnt-inducible signaling pathway protein-1 (Wisp-1, also known as CCN4) belongs to the CCN gene family, which contains cysteine-rich 61 (Cyr61/CCN1), connective tissue growth factor (CTGF/CCN2), nephroblastoma overexpressed (NOV/CCN3), Wisp-1/CCN4, Wisp-2/CCN5, and Wisp-3/CCN6. This gene family encodes secreted proteins that interact with the extracellular matrix and have important roles in migration, adhesion, proliferation, apoptosis, survival, inflammation, and injury repair. Wisp-1 is highly expressed in several pathologic conditions characterized by fibrosis, such as the idiopathic pulmonary fibrosis, and induces the expression of extracellular matrix components, such as type-I collagen and fibronectin in lung fibroblasts. It has been reported that Wisp-1 is strongly up-regulated in the synovial membrane and articular cartilage of patients with osteoarthritis and is able to induce the production of IL-6 from synovial fibroblasts and elicit the release of MMPs and aggrecanase from macrophages and chondrocytes, which cause cartilage damage. In addition, it appears that a functional relationship between Wisp-1 and TGF-β1 signaling pathways occurs, since Wisp-1 significantly reduces TGF-β1-induced phosphorylation of SMAD-2, while TGF-β1 stimulates the canonical Wnt-1 signaling pathway through the suppression of Wnt-1 antagonist, Dickkopf-1, leading to stimulation of Wisp-1 expression. The aim of this work was the investigation of Wnt-1 and TGF-β1 expression in nasal polyps and pterygium tissues in comparison with normal nasal mucosa and conjunctiva, respectively, as well as the study of Wisp-1 effects on the expression of various extracellular matrix components in nasal polyps and pterygium fibroblast, having on mind the known effects of Wisp-1 on synovial fibroblasts. Nasal polyps were resected by functional endoscopic sinus surgery from patients suffered from chronic sinusitis with polyposis. The control group consisted of healthy subjects from whom healthy nasal mucosa was taken during nasal septoplasty-inferior turbinoplasty. Pterygium specimens were obtained after the surgical removal of primary pterygium. Specimens of normal human conjunctiva were obtained from healthy donors, during cataract surgery. Synovial membranes were obtained from patients with osteoarthritis subjected in total knee arthroplasty. Fibroblasts were isolated from all the above tissues upon mild treatment by clostridium collagenase. The levels of IL-6 and MIF in cell cultures conditioned media were determined by ELISA. The expression of IL-6, type-I collagen and TIMP-1 in cultured fibroblasts or of TGF-β1 and Wnt-1 in tissues was ascertained by semi-quantitative RT-PCR. RT-PCR analysis showed that Wnt-1 is expressed in pterygium as well as in nasal polyps. The expression of Wnt-1 was higher in normal conjunctiva than in pterygium. On the contrary, the expression of Wnt-1 was higher in polyps than in normal nasal mucosa. On the other hand, RT-PCR analysis showed also that the expression of TGF-β1 was higher in normal nasal mucosa than in polyps, while was not observed statistically significant difference in the expression of TGF-β1, between pterygium and normal conjunctiva. Culture of fibroblasts in the presence of rhWisp-1 showed that it caused up-regulation of IL-6 expression in synovial and pterygium fibroblasts but down-regulation in polyps fibroblasts, in a dose-depended manner. It is noticed that Wisp-1 did not affect the expression of IL-6 in normal mucosa and conjunctiva fibroblasts. When fibroblasts were cultured in the presence of TGF-β1, alone or together with Wisp-1, a suppression of TGF-β1-induced expression of IL-6 in polyps and synovial fibroblasts by Wisp-1 was observed, while it had not any effect on TGF-β1-induced expression of IL-6 in pterygium fibroblasts. Wisp-1 caused also up-regulation of TIMP-1 in both the polyps and pterygium fibroblast in a dose-depended manner, while it suppressed the TGF-β1-induced expression of TIMP-1 in both fibroblasts. Similarly, Wisp-1 caused up-regulation of type-I collagen in both the polyps and pterygium fibroblast in a dose-depended manner, however, it suppressed the TGF-β1-induced expression of type-I collagen only in pterygium fibroblasts, while it did not affect this TGF-β1 effect in polyps fibroblasts. In addition, Wisp-1 caused significant up-regulation of MIF production from all the three kinds of fibroblasts tested, in a dose-depended mode. Wisp-1 is reported to be a Wnt target. The Wnt/β-catenin pathway may be expressed and is operative in nasal polyps and pterygium. It is possible that an initial injury, caused by UV irradiation in pterygium or by various factors in nasal polyps, leads to Wisp-1 increased expression by epithelial cells. By exception of polyps fibroblasts, regarding the expression of IL-6, the released Wisp-1 subsequently, through paracrine effects, stimulates the stromal fibroblasts to produce factors that may contribute in the extracellular matrix accumulation and fibrosis. On the other hand, Wisp-1 suppresses the TGF-β1-induced production of the same factors from stromal fibroblasts and induces the production of MIF, a known pro-inflammatory factor, from these cells. A such effect of Wisp-1 is presented for the first time in literature. Taken to account all these observations, it is not possible, at the present time, to express an opinion related to exactly role of Wisp-1 in polyps and pterygium formation and development." @default.
• W2968103410 created "2019-08-22" @default.
• W2968103410 creator A5008012704 @default.
• W2968103410 date "2017-05-14" @default.
• W2968103410 modified "2023-09-23" @default.
• W2968103410 title "Eπίδραση της επαγόμενης απο Wnt-1 πρωτεΪνης-1 (Wisp-1) στην έκφραση συστατικών του εξωκυττάριου χώρου σε ινοβλάστες αρθρικού υμένα, ρινικού πολύποδα και πτερυγιού οφθαλμού ανθρώπου" @default.
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