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

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 α1-adrenoceptor (α1-AR) antagonists inhibit mesangial cell (MC) proliferation. Howeve...

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Main Authors: Fanwu Kong, Linlin Ma, Li Zou, Kexin Meng, Tianrong Ji, Lei Zhang, Rui Zhang, Jundong Jiao
Format: Article
Language:English
Published: Cell Physiol Biochem Press GmbH & Co KG 2015-07-01
Series:Cellular Physiology and Biochemistry
Subjects:
Online Access:http://www.karger.com/Article/FullText/430161
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author Fanwu Kong
Linlin Ma
Li Zou
Kexin Meng
Tianrong Ji
Lei Zhang
Rui Zhang
Jundong Jiao
author_facet Fanwu Kong
Linlin Ma
Li Zou
Kexin Meng
Tianrong Ji
Lei Zhang
Rui Zhang
Jundong Jiao
author_sort Fanwu Kong
collection DOAJ
description 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 α1-adrenoceptor (α1-AR) antagonists inhibit mesangial cell (MC) proliferation. However, the underlying mechanism remains unclear. Methods and Results: We found that α1-AR is expressed in a human mesangial cell line. The α1-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 α1-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 abrogated PE-induced ERK1/2 phosphorylation. Conclusion: TRPC6 channels are involved in α1-AR activation-induced Ca2+ entry, which mediates proliferation via ERK signaling in human MCs
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spelling doaj.art-ad96e13b27404ea88c4303d4c9aad1022022-12-22T02:16:44ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782015-07-013651928193810.1159/000430161430161Alpha1-Adrenergic Receptor Activation Stimulates Calcium Entry and Proliferation via TRPC6 Channels in Cultured Human Mesangial CellsFanwu KongLinlin MaLi ZouKexin MengTianrong JiLei ZhangRui ZhangJundong JiaoBackground 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 α1-adrenoceptor (α1-AR) antagonists inhibit mesangial cell (MC) proliferation. However, the underlying mechanism remains unclear. Methods and Results: We found that α1-AR is expressed in a human mesangial cell line. The α1-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 α1-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 abrogated PE-induced ERK1/2 phosphorylation. Conclusion: TRPC6 channels are involved in α1-AR activation-induced Ca2+ entry, which mediates proliferation via ERK signaling in human MCshttp://www.karger.com/Article/FullText/430161AdrenoceptorERK signalingTRPC6Mesangial cells
spellingShingle Fanwu Kong
Linlin Ma
Li Zou
Kexin Meng
Tianrong Ji
Lei Zhang
Rui Zhang
Jundong Jiao
Alpha1-Adrenergic Receptor Activation Stimulates Calcium Entry and Proliferation via TRPC6 Channels in Cultured Human Mesangial Cells
Cellular Physiology and Biochemistry
Adrenoceptor
ERK signaling
TRPC6
Mesangial cells
title Alpha1-Adrenergic Receptor Activation Stimulates Calcium Entry and Proliferation via TRPC6 Channels in Cultured Human Mesangial Cells
title_full Alpha1-Adrenergic Receptor Activation Stimulates Calcium Entry and Proliferation via TRPC6 Channels in Cultured Human Mesangial Cells
title_fullStr Alpha1-Adrenergic Receptor Activation Stimulates Calcium Entry and Proliferation via TRPC6 Channels in Cultured Human Mesangial Cells
title_full_unstemmed Alpha1-Adrenergic Receptor Activation Stimulates Calcium Entry and Proliferation via TRPC6 Channels in Cultured Human Mesangial Cells
title_short Alpha1-Adrenergic Receptor Activation Stimulates Calcium Entry and Proliferation via TRPC6 Channels in Cultured Human Mesangial Cells
title_sort alpha1 adrenergic receptor activation stimulates calcium entry and proliferation via trpc6 channels in cultured human mesangial cells
topic Adrenoceptor
ERK signaling
TRPC6
Mesangial cells
url http://www.karger.com/Article/FullText/430161
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