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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Cell Physiol Biochem Press GmbH & Co KG
2015-07-01
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Series: | Cellular Physiology and Biochemistry |
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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 |
first_indexed | 2024-04-14T02:43:46Z |
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id | doaj.art-ad96e13b27404ea88c4303d4c9aad102 |
institution | Directory Open Access Journal |
issn | 1015-8987 1421-9778 |
language | English |
last_indexed | 2024-04-14T02:43:46Z |
publishDate | 2015-07-01 |
publisher | Cell Physiol Biochem Press GmbH & Co KG |
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series | Cellular Physiology and Biochemistry |
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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