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Advanced glycation end products promote proliferation of cardiac fibroblasts by upregulation of KCa3.1 channels

  • Ion channels, receptors and transporters
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Abstract

The present study was designed to investigate whether advanced glycation end products (AGEs) would regulate KCa3.1 channels in cardiac fibroblasts and participate in cell proliferation. Cultured adult rat cardiac fibroblasts were employed to investigate the regulation of KCa3.1 channels by advanced glycation end products–bovine serum albumin (AGE–BSA) and the role of KCa3.1 channels in cell proliferation using approaches of molecular biology. KCa3.1 channel mRNA and protein levels were greatly enhanced in cardiac fibroblasts treated with 200 μg/ml AGE–BSA, and the effects were countered by anti-RAGE antibody or the ERK1/2 inhibitor PD98059, the p38-MAPK inhibitor SB203580, and the PI3K/Akt inhibitor LY294002. In addition, AGE–BSA stimulated cell proliferation and collagen production in cultured cardiac fibroblasts, and the effects were reversed by KCa3.1 blocker TRAM-34, anti-RAGE antibody, or signal inhibitors PD98059, SB203580, and LY294002. These results demonstrate for the first time that AGEs increase the expression of KCa3.1 channels in a RAGE-dependent manner and promote cardiac fibroblast proliferation and collagen production, which is mediated by phosphorylation of ERK1/2, p38-MAPK, and PI3K/Akt signals.

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Acknowledgments

This work was supported by the National Nature Science Foundation of China (grant number 81100231), the National Nature Science Foundation of Shaanxi Province (grant number 2011JQ4021), and China Postdoctoral Science Foundation (grant number 20100481335).

Conflict of interest

None declared.

Ethical standards

Experimental protocols were approved by the Institutional Animal Care and Use Committee of Xi’an Jiaotong University and conformed to the Guide for the Care and Use of Laboratory Animals published by the National Institutes of Health, USA.

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Authors and Affiliations

  1. Department of Physiology and Pathophysiology, School of Medicine, Xi’an Jiaotong University, 76 West Yanta Road, Xi’an, 710061, Shaanxi, China

    Li-Mei Zhao, Wei Zhang, Li-Ping Wang & Xiu-Ling Deng

  2. Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China

    Gui-Rong Li

  3. Department of Physiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China

    Gui-Rong Li

  4. Cardiovascular Research Center, School of Medicine, Xi’an Jiaotong University, 76 West Yanta Road, Xi’an, 710061, Shaanxi, China

    Xiu-Ling Deng

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  1. Li-Mei Zhao
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  2. Wei Zhang
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Correspondence to Xiu-Ling Deng.

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Zhao, LM., Zhang, W., Wang, LP. et al. Advanced glycation end products promote proliferation of cardiac fibroblasts by upregulation of KCa3.1 channels. Pflugers Arch - Eur J Physiol 464, 613–621 (2012). https://doi.org/10.1007/s00424-012-1165-0

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  • DOI: https://doi.org/10.1007/s00424-012-1165-0

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