CircTHBS1 aggravates peritoneal fibrosis by sponging miR-18a-5p and interacting with CTGF

Peritoneal fibrosis is a serious complication of long-term peritoneal dialysis (PD). Previous studies have demonstrated that circular RNAs (circRNAs) play an important role in organ fibrosis. However, whether circRNAs are involved in the progression of peritoneal fibrosis remains largely elusive. This study aimed to investigate the role of circRNAs in peritoneal fibrosis and clarify the underlying mechanisms.

CircRNA expression in peritoneal mesothelial cells derived from peritoneal dialysis effluent was profiled using a human circRNA microarray. The function of circTHBS1 was studied through gene silencing and overexpression. qRT-PCR and western blotting were used to detect the expression of relevant molecules. PD mouse models with adeno-associated virus (AAV)-mediated circTHBS1 knockdown were established to investigate the role of circTHBS1 in peritoneal fibrosis using histological staining and peritoneal function analyses.

CircTHBS1 was significantly upregulated in peritoneal mesothelial cells from long-term PD patients and was positively correlated with the expression of fibronectin, alpha-smooth muscle actin (α-SMA), and connective tissue growth factor (CTGF). Silencing circTHBS1 suppressed epithelial-mesenchymal transition (EMT) in HMrSV5 cells. In vivo, circTHBS1 knockdown significantly alleviated peritoneal thickening and fibrosis, lowered α-SMA expression, and improved peritoneal function in PD mice. Mechanistically, circTHBS1 acted as a sponge for miR-18a-5p, relieving its repression of CTGF, and directly interacted with CTGF, thereby enhancing its stability. CTGF silencing partially attenuated EMT induced by circTHBS1 overexpression and miR-18a-5p inhibition.

This study suggests that circTHBS1 could be a candidate target for the treatment of peritoneal fibrosis.