Journal
JOURNAL OF CELLULAR PHYSIOLOGY
Volume 235, Issue 3, Pages 2009-2022Publisher
WILEY
DOI: 10.1002/jcp.29187
Keywords
autophagy; renal fibrosis; TGF-beta 1; unilateral ureteral obstruction; WISP-1
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Funding
- West Light of Young Scholars Project 2018
- National Natural Science Foundation of China [81300618, 81970641]
- Sichuan Provincial Planning Commission Fund [17PJ058]
- Sichuan Provincial People's Hospital Research Foundation [2016LY07]
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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-beta 1 (TGF-beta 1)-induced production of fibrotic markers, including collagen I (Col I), fibronectin (FN) and TGF-beta 1, 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-beta 1. 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-beta 1-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-beta 1-treated TECs. WISP-1 may serve as an effective therapeutic target for the treatment of renal fibrosis.
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