Pflügers Archiv - European Journal of Physiology

, Volume 464, Issue 6, pp 613–621

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

  • Li-Mei Zhao
  • Wei Zhang
  • Li-Ping Wang
  • Gui-Rong Li
  • Xiu-Ling Deng
Ion channels, receptors and transporters

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.

Keywords

Intermediate-conductance Ca2+-activated K+ channel Advanced glycation end products Cardiac fibroblasts Proliferation 

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Li-Mei Zhao
    • 1
  • Wei Zhang
    • 1
  • Li-Ping Wang
    • 1
  • Gui-Rong Li
    • 2
    • 3
  • Xiu-Ling Deng
    • 1
    • 4
  1. 1.Department of Physiology and Pathophysiology, School of MedicineXi’an Jiaotong UniversityXi’anChina
  2. 2.Department of Medicine, Li Ka Shing Faculty of MedicineThe University of Hong KongPokfulamChina
  3. 3.Department of Physiology, Li Ka Shing Faculty of MedicineThe University of Hong KongPokfulamChina
  4. 4.Cardiovascular Research Center, School of MedicineXi’an Jiaotong UniversityXi’anChina

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