Liyin Chai, Binying Zhang, Zhengyang Liu, Jun Zeng, Xingqing Chen, Li Gong, Fang Wang*
Published October 28, 2024
Genet. Mol. Res. 23 (4): gmr2372
http://dx.doi.org/10.4238/gmr2372
About the Authors
Liyin Chai, Binying Zhang, Zhengyang Liu, Jun Zeng, Xingqing Chen, Li Gong, Fang Wang*
Corresponding author:
Fang Wang
E-mail: 16314645@qq.com
ABSTRACT
Autosomal Dominant Polycystic Kidney Disease (ADPKD), a prevalent hereditary disorder, involves the Transient Receptor Potential Canonical 6 (TRPC6) protein, a key factor in disease progression. This study aimed to determine the effects of TRPC6 gene suppression on the proliferation and matrix production of ADPKD cyst-lining epithelial cells. The polycystic kidney wall lining inner epithelial cell line WT9-12 (WT9-12) cell line was treated with TRPC6-siRNA, and cell behavior was analyzed using the CCK-8 assay and flow cytometry. Expression levels of TRPC6 and matrix proteins (Type I Collagen (Col I), Type IV Collagen (Col IV), Procollagen III, and N-terminal Propeptide (PⅢNP) Collagen) were measured by Real-Time Fluorescence Quantitative PCR and Enzyme-Linked Immunosorbent Assay. Signaling proteins related to cell proliferation and apoptosis were assessed by Western blot. TRPC6 silencing significantly decreased WT9-12 cell proliferation and matrix secretion, particularly Col I and Col IV. Apoptosis-related proteins, cleaved caspase 3 and 9, increased post-silencing, with Bax up-regulated and Bcl-2 and p-ERK down-regulated (P<0.05). The activity of p38, p-p38, JNK, p-JNK, and ERK showed no significant change (P>0.05). These results suggest that TRPC6 gene silencing can inhibit epithelial cell proliferation and matrix production in ADPKD, and thus present a promising therapeutic strategy.
Key words: ADPKD; TRPC6; Proliferation; Apoptosis; Stromal secretion of epithelial cells