The impact of silencing TRPC6 on the proliferation, apoptosis, and extracellular matrix secretion of epithelial cells lining the cyst wall in ADPKD

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.