| First Author | Yang X | Year | 2020 |
| Journal | J Cell Physiol | Volume | 235 |
| Issue | 3 | Pages | 2009-2022 |
| PubMed ID | 31512238 | Mgi Jnum | J:299788 |
| Mgi Id | MGI:6490671 | Doi | 10.1002/jcp.29187 |
| Citation | Yang X, et al. (2020) WNT1-inducible signaling protein-1 mediates TGF-beta1-induced renal fibrosis in tubular epithelial cells and unilateral ureteral obstruction mouse models via autophagy. J Cell Physiol 235(3):2009-2022 |
| abstractText | Renal fibrosis is a common pathway for the progression of all chronic kidney diseases to end-stage kidney disease. Studies show that WNT1-inducible signaling pathway protein-1 (WISP-1) is involved in the fibrosis of various organs. The aim of the study was to explore the functional role and potential mechanism of WISP-1 in renal fibrosis. We observed that overexpression of WISP-1 in rat tubular epithelial cells (TECs) enhanced transforming growth factor-beta1 (TGF-beta1)-induced production of fibrotic markers, including collagen I (Col I), fibronectin (FN) and TGF-beta1, while inhibition of WISP-1 suppressed such production. In vivo, the messenger RNA and protein levels of Col I, FN, and alpha-smooth muscle actin were significantly inhibited after anti-WISP-1 antibody treatment for 7 days in unilateral ureteral obstruction mouse models. Moreover, blockade of WISP-1 by anti-WISP-1 antibody significantly reduced autophagy-related markers, including anti-microtubule-associated protein-1 light chain 3 (LC3) and beclin 1, while increasing sequestosome 1. In addition, overexpression of WISP-1 in TECs increased autophagy as evidenced by greater numbers of GFP-LC3 puncta and increased expression of LC3 and beclin 1 in response to TGF-beta1. In contrast, knockdown of WISP-1 by small interfering RNA decreased the number of GFP-LC3 puncta and the expression of LC3 and beclin 1 in TGF-beta1-treated TECs. Collectively, these data suggest that WISP-1, as a profibrotic protein, may mediate renal fibrosis by inducing autophagy in both obstructive nephropathy and TGF-beta1-treated TECs. WISP-1 may serve as an effective therapeutic target for the treatment of renal fibrosis. |
