Beyond Gap Junction Channel Function: the Expression of Cx43 Contributes to Aldosterone-Induced Mesangial Cell Proliferation via the ERK1/2 and PKC Pathways
Aims: This study aimed to explore the precise mechanism and signaling pathways of mesangial cell (MC) proliferation from a new point of view considering Connexin 43 (Cx43). Methods: MC proliferation was measured by the incorporation of 3H-thymidine (3H-TdR). Cx43 was over-expressed in MC cells using...
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Cell Physiol Biochem Press GmbH & Co KG
2015-06-01
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doaj-6ea4e643d7254f0b835bc85db036ab502020-11-25T01:38:00ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782015-06-013631210122210.1159/000430291430291Beyond Gap Junction Channel Function: the Expression of Cx43 Contributes to Aldosterone-Induced Mesangial Cell Proliferation via the ERK1/2 and PKC PathwaysAiqing ZhangYing HanBin WangShanwen LiWeihua GanAims: This study aimed to explore the precise mechanism and signaling pathways of mesangial cell (MC) proliferation from a new point of view considering Connexin 43 (Cx43). Methods: MC proliferation was measured by the incorporation of 3H-thymidine (3H-TdR). Cx43 was over-expressed in MC cells using lipofectamine 2000, and the expression level was tested with reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses. The gap junction channel function was explored by Lucifer Yellow scrape loading and dye transfer (SLDT), and the intracellular calcium concentrations ([Ca2+]i) were characterized by confocal microscopy on cells loaded with Fura-3/AM. Results: There was an inverse correlation between Cx43 expression and MC proliferation (P0.05). Our data also showed that the mineralcorticoid receptor (MR) antagonist spironolactone, ERK1/2 inhibitor PD98059 and PKC inhibitor GF109203X could attenuate the down-regulation of Cx43 expression in Aldo-induced MC proliferation; however, the PI3K inhibitor LY294002 could block MC proliferation without affecting Cx43 expression at either the mRNA or protein level. In addition, Aldo promoted MC proliferation in parallel with increasing [Ca2+]i (PConclusions: Our study provides preliminary evidence that Cx43 is an important regulator of Aldo-promoted MC proliferation. Furthermore, reduced Cx43 expression promoted MC proliferation independent of the gap junction channel function, and this process might be mediated through the ERK1/2- and PKC-dependent pathways.http://www.karger.com/Article/FullText/430291Connexin 43Gap junctionMesangial cellsProliferation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Aiqing Zhang Ying Han Bin Wang Shanwen Li Weihua Gan |
spellingShingle |
Aiqing Zhang Ying Han Bin Wang Shanwen Li Weihua Gan Beyond Gap Junction Channel Function: the Expression of Cx43 Contributes to Aldosterone-Induced Mesangial Cell Proliferation via the ERK1/2 and PKC Pathways Cellular Physiology and Biochemistry Connexin 43 Gap junction Mesangial cells Proliferation |
author_facet |
Aiqing Zhang Ying Han Bin Wang Shanwen Li Weihua Gan |
author_sort |
Aiqing Zhang |
title |
Beyond Gap Junction Channel Function: the Expression of Cx43 Contributes to Aldosterone-Induced Mesangial Cell Proliferation via the ERK1/2 and PKC Pathways |
title_short |
Beyond Gap Junction Channel Function: the Expression of Cx43 Contributes to Aldosterone-Induced Mesangial Cell Proliferation via the ERK1/2 and PKC Pathways |
title_full |
Beyond Gap Junction Channel Function: the Expression of Cx43 Contributes to Aldosterone-Induced Mesangial Cell Proliferation via the ERK1/2 and PKC Pathways |
title_fullStr |
Beyond Gap Junction Channel Function: the Expression of Cx43 Contributes to Aldosterone-Induced Mesangial Cell Proliferation via the ERK1/2 and PKC Pathways |
title_full_unstemmed |
Beyond Gap Junction Channel Function: the Expression of Cx43 Contributes to Aldosterone-Induced Mesangial Cell Proliferation via the ERK1/2 and PKC Pathways |
title_sort |
beyond gap junction channel function: the expression of cx43 contributes to aldosterone-induced mesangial cell proliferation via the erk1/2 and pkc pathways |
publisher |
Cell Physiol Biochem Press GmbH & Co KG |
series |
Cellular Physiology and Biochemistry |
issn |
1015-8987 1421-9778 |
publishDate |
2015-06-01 |
description |
Aims: This study aimed to explore the precise mechanism and signaling pathways of mesangial cell (MC) proliferation from a new point of view considering Connexin 43 (Cx43). Methods: MC proliferation was measured by the incorporation of 3H-thymidine (3H-TdR). Cx43 was over-expressed in MC cells using lipofectamine 2000, and the expression level was tested with reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses. The gap junction channel function was explored by Lucifer Yellow scrape loading and dye transfer (SLDT), and the intracellular calcium concentrations ([Ca2+]i) were characterized by confocal microscopy on cells loaded with Fura-3/AM. Results: There was an inverse correlation between Cx43 expression and MC proliferation (P0.05). Our data also showed that the mineralcorticoid receptor (MR) antagonist spironolactone, ERK1/2 inhibitor PD98059 and PKC inhibitor GF109203X could attenuate the down-regulation of Cx43 expression in Aldo-induced MC proliferation; however, the PI3K inhibitor LY294002 could block MC proliferation without affecting Cx43 expression at either the mRNA or protein level. In addition, Aldo promoted MC proliferation in parallel with increasing [Ca2+]i (PConclusions: Our study provides preliminary evidence that Cx43 is an important regulator of Aldo-promoted MC proliferation. Furthermore, reduced Cx43 expression promoted MC proliferation independent of the gap junction channel function, and this process might be mediated through the ERK1/2- and PKC-dependent pathways. |
topic |
Connexin 43 Gap junction Mesangial cells Proliferation |
url |
http://www.karger.com/Article/FullText/430291 |
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