TRPC 促进肾小球系膜细胞外基质沉积的机制研究

Objective To explore the role and mechanism of TRPC in promoting extracellular matrix (ECM) deposition in rat glomerular mesangial cells (HBZY-1).Methods Immunofluorescence staining was performed to observe the distribution and expression of TRPC1 and TRPC6 in HBZY-1 cells. After Angll stimulation, qRT-PCR and Western blotting were used to detect the mRNA and protein expressions of Gaq/PLCP4/TRPC signaling pathway main proteins and ECM deposition indicators (n-SMA, collagen HI and fibronectin).By silencing the expressions of TRPC1 and TRPC6 by RNA interference, the expressions of ECM deposition indicators were detected. Changes in [Ca²⁺+]i influx were determined through Fluo-4AM Ca²⁺+ imaging. Results Both TRPC1 and TRPC6 were expressed in HBZY-1, and were mainly located in cell membrane and cytoplasm. After Ang II stimulation, Gaq/PLCP4/TRPC signaling pathway was activated, and the mRNA and protein expressions of Gaq, PLCP4, TRPC1 andTRPC6 were all increased (P<0.05).[Ca²⁺~]i influx also increased (P<0.01), and the mRNA and protein expressions of ECM deposition indicators (a-SMA, ColH[and Fn) were upregulated (P<0.05).Silencing the expressions of TRPC1 and TRPC6 by RNA interference led to decreased [Ca²⁺~]i influx (P<0.05), and downregulated mRNA and protein expressions of ECM deposition indicators in HBZY-1 cells (P<0.05).The results suggested that inhibition of TRPC expressions could inhibit Ang II induced ECM deposition in HBZY-1 cells, which might be associated with decreased [Ca²⁺+]i influx. Conclusion TRPC may be a novel therapeutic target of renal fibrosis.