Alpha1-Adrenergic Receptor Activation Stimulates Calcium Entry and Proliferation via TRPC6 Channels in Cultured Human Mesangial Cells

作者：Kong, Fanwu; Ma, Linlin; Zou, Li; Meng, Kexin; Ji, Tianrong; Zhang, Lei; Zhang, Rui; Jiao, Jundong^*

来源：Cellular Physiology and Biochemistry, 2015, 36(5): 1928-1938.

DOI：10.1159/000430161

• TRPC6
• Mesangial cells
• Adrenoceptor
• ERK signaling

Background and Aims: There is accumulating evidence that sympathetic nervous hyperactivity contributes to the pathogenesis of glomerular sclerosis independent of blood pressure effects. A previous study showed that alpha(1)-adrenoceptor (alpha(1)-AR) antagonists inhibit mesangial cell (MC) proliferation. However, the underlying mechanism remains unclear. Methods and Results: We found that alpha(1)-AR is expressed in a human mesangial cell line. The alpha(1)-AR agonist phenylephrine (PE) induced Ca2+ influx as well as release from intracellular Ca2+ stores. Blockade of TRPC6 with siRNA, anti-TRPC6 antibodies and a TRPC blocker attenuated the PE-induced [Ca2+](i) increase. Additionally, the PE-induced [Ca2+](i) increase was phospholipase C dependent. Furthermore, PE induced a [Ca2+](i) increase even when the intracellular Ca2+ stores were already depleted. This effect was mimicked by an analog of diacylglycerol. These results suggested that, upon alpha(1)-AR stimulation, TRPC6 mediates Ca2+ influx via a receptor-operated Ca2+ entry mechanism. Finally, TRPC6 contributes to the PE-induced MC proliferation. The mechanisms are associated with the extracellular signal-regulated kinase (ERK) signaling pathway because blockade of TRPC6 and chelation of extracellular Ca2+ abrogated PE-induced ERK1/2 phosphorylation. Conclusion: TRPC6 channels are involved in alpha(1)-AR activation-induced Ca2+ entry, which mediates proliferation via ERK signaling in human MCs.

• 出版日期2015
• 单位哈尔滨医科大学