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Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

1 Jan 2016Article

Phenylephrine promotes cardiac fibroblast proliferation through calcineurin-NFAT pathway

Jing Wang 1,2, Yibing Wang 3, Wei Zhang 2,4, Xi Zhao 2, Xiangfan Chen 2, Wenyan Xiao 2, Lingling Zhang 2, Yunxuan Chen 2, Weizhong Zhu 2,4,*
Affiliations
Article Info

1 Department of Pharmacy, Nantong University Affiliated Hospital, Nantong, P. R. China

2 Department of Pharmacology, Nantong University School of Pharmacy, Nantong, P. R. China

3 Department of Pharmacy, Yan Cheng Institute of Health Science, Nantong University, Nantong, P. R. China

4 Key lab of inflammation and drug target, Jiangsu province, Nantong University, Nantong, P. R. China

Abstract

Ca2+/calmodulin-dependent calcineurin (CaN) plays an important role in various Ca2+ signaling pathways, among which are those involved in cardiac diseases. It has also been shown that a heightened sympathetic tone accelerates the development of heart failure. The present study investigates whether the CaN-mediated nuclear factor of activated T-cells (NFAT) pathway is involved in cultured neonatal rat cardiac fibroblast proliferation induced by phenylephrine. CF proliferation was assessed by a cell survival assay and cell counts. Green fluorescent protein-tagged NFAT3 was used to determine the cellular location of NFAT3. CaN activity and protein levels were also determined by an activity assay kit and Western blotting, respectively. Results showed that phenylephrine promoted CF proliferation, which was abolished by α1-adrenergic receptor antagonist (prazosin), a blocker of Ca2+ influx (nifedipine), an intracellular Ca2+ buffer (BAPTA-AM), CaN inhibitors (cyclosporin A and FK506), and over-expression of dominant negative CaN. Phenylephrine activated CaN and evoked NFAT3 nuclear translocation, both of which were blocked by cyclosporine A (CsA) or over-expression of dominant negative CaN. These results suggest that the Ca2+/CaN/NFAT pathway mediates PE-induced CF proliferation, and this pathway might be a possible therapeutic target in cardiac fibrosis.

Keywords

  • Calcineurin
  • Phenylephrine
  • Nuclear factor of activated T cells
  • Proliferation
  • Fibroblast

References