Mechanism of TRPC in promoting extracellular matrix deposition of glomerular mesangial cells

Linting Wei; Pengbo GE; Ke LI; Yan LI; Yinhong Wang; Weihao Zhao; Chenkai Cui; Jing Dong; Jie Gao; Li Wang; Rongguo FU

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Mechanism of TRPC in promoting extracellular matrix deposition of glomerular mesangial cells

VernacularTitle:TRPC促进肾小球系膜细胞外基质沉积的机制研究
Author: Linting WEI ¹ ; Pengbo GE ² ; Ke LI ¹ ; Yan LI ¹ ; Yinhong WANG ¹ ; Weihao ZHAO ¹ ; Chenkai CUI ¹ ; Jing DONG ¹ ; Jie GAO ¹ ; Li WANG ¹ ; Rongguo FU ¹
Author Information

1. Department of Nephrology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004
2. Department of General Surgery, The First Affiliated Hospital of Xi’an Medical College, Xi’an 710077, China
Publication Type:Journal Article
Keywords: TRPC; AngⅡ; glomerular mesangial cell; ECM deposition; renal fibrosis
From: Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(4):518-524
CountryChina
Language:Chinese
Abstract: 【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 AngⅡ stimulation, qRT-PCR and Western blotting were used to detect the mRNA and protein expressions of Gαq/PLCβ4/TRPC signaling pathway main proteins and ECM deposition indicators (α-SMA, collagenⅢ 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 AngⅡ stimulation, Gαq/PLCβ4/TRPC signaling pathway was activated, and the mRNA and protein expressions of Gαq, PLCβ4, TRPC1 and TRPC6 were all increased (P<0.05). [Ca²⁺]i influx also increased (P<0.01), and the mRNA and protein expressions of ECM deposition indicators (α-SMA, ColⅢ 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 AngⅡ 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.