CCN family, a group of six extracellular matrix-associated proteins, plays an important role in fibrosis. WISP3 has addressed as a pro-fibrotic molecule in the development of human lung fibrosis. However, whether WISP3 involved in the activation and proliferation of renal fibroblast, and ultimately inhibited fibroblast-myofibroblast transdifferentiation remained unknown. Herein, we found that down-regulated WISP3 was involved in the fibrogenesis of rat renal NRK-49F cells induced by transforming growth (TGF-beta 1), which was further confirmed in a rat renal fibrosis induced by unilateral ureteral obstruction (UUO). In the present study, we aimed to investigate the roles of WISP3 in NRK-49F fibroblast-myofibroblast transdifferentiation, and the underlying mechanism. Results showed that after TGF-beta 1 treatment, significant increased cell proliferation, and up-regulated expressions of TGF-beta 1, connective tissue growth factor (CTGF), alpha-smooth muscle actin (alpha-SMA), vimentin, as well as increased concentrations of collagen types I (COL I), collagen types III (COL III) and hydroxyproline in cell culture supernatant were observed, demonstrating a successful establishment of fibroblast-myofibroblast transdifferentiation of NRK-49F cells. Besides, siRNA-WISP3 remarkably promoted the fibrogenesis of NRK-49F cells with or without TGF-beta 1 treatment, and increased mRNA levels of Axin, demonstrating that activating WNT signaling pathway was the underlying mechanism. However, lentivirus-mediated WISP3 overexpression exerted an opposite effect, protecting NRK-49F cells from transdifferentiation, and decreasing mRNA levels of Axin. In conclusion, the WISP3 played an anti-fibrotic role in NRK-49F cells, and WNT signaling pathway was the potential mechanism. WISP3 was an anti-fibrotic factor in fibroblast-myofibroblast transdifferentiation, and may be used as a possible target for prevention and treatment of human renal fibrosis.
[1]Fudan Univ, Huashan Hosp, Jingan Dist Cent Hosp, Dept Nephrol,Jingan Branch, Shanghai 200040, Peoples R China.
[2]Shanghai Univ Tradit Chinese Med, Peoples Hosp 7, Shanghai 200137, Peoples R China.
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