open access

Vol 27, No 2 (2020)
Original articles — Basic science and experimental cardiology
Published online: 2019-05-13
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Transient receptor potential channel TRPV4 mediates TGF-β1-induced differentiation of human ventricular fibroblasts

Min-Soo Ahn, Young Woo Eom, Ji-Eun Oh, Seung-Kuy Cha, Kyu Sang Park, Jung-Woo Son, Jun-Won Lee, Young Jin Youn, Sung Gyun Ahn, Jang-Young Kim, Seung-Hwan Lee, Junghan Yoon, Byung-Su Yoo
DOI: 10.5603/CJ.a2019.0050
·
Pubmed: 32329036
·
Cardiol J 2020;27(2):162-170.

open access

Vol 27, No 2 (2020)
Original articles — Basic science and experimental cardiology
Published online: 2019-05-13

Abstract

Background: Cardiac fibroblasts (CFs) are principal extracellular matrix-producing cells. In response to injury, CFs transdifferentiate into myofibroblasts. Intracellular calcium (Ca2+) signaling, involved in fibroblast proliferation and differentiation, is activated in fibroblasts through transient receptor potential (TRP) channels, but the function of these channels has not been investigated in human ventricular CFs. Under evaluation in this study, was the role of TRP channels in the differentiation of human ventricular CFs induced by transforming the growth factor beta (TGF-β), a pro-fibrotic cytokine.

Methods: Human ventricular CFs were used in this study. The differentiation of CFs into myofibroblast was induced with TGF-β and was identified by the expression of smooth muscle actin.

Results: Results indicate that Ca2+ signaling was an essential component of ventricular CF dif­ferentiation. CFs treated with TGF-β demonstrated increased expression of a TRP channel, TRPV4, both at the mRNA and protein levels, which corresponded with CF-myofibroblast trans-differentiation, as evidenced by the upregulation of α-smooth muscle actin, a myofibroblast marker, and plasminogen activator inhibitor-1, which are fibrogenesis markers. An agonist of TRPV4 induced the conversion of CFs into myofibroblasts, whereas it’s antagonist as well a Ca2+ chelating agent reduced it, indicating that the Ca2+ influx throughTRPV4 is required for CF trans-differentiation. Overall, these results dem­onstrate that TRPV4-mediated Ca2+ influx participates in regulating the differentiation of human ventricular CFs into myofibroblasts through the MAPK/ERK pathway.

Conclusions: Overall, these results demonstrate that TRPV4-mediated Ca2+ influx participates in regulating the differentiation of human ventricular CFs into myofibroblasts through the MAPK/ERK pathway.

Abstract

Background: Cardiac fibroblasts (CFs) are principal extracellular matrix-producing cells. In response to injury, CFs transdifferentiate into myofibroblasts. Intracellular calcium (Ca2+) signaling, involved in fibroblast proliferation and differentiation, is activated in fibroblasts through transient receptor potential (TRP) channels, but the function of these channels has not been investigated in human ventricular CFs. Under evaluation in this study, was the role of TRP channels in the differentiation of human ventricular CFs induced by transforming the growth factor beta (TGF-β), a pro-fibrotic cytokine.

Methods: Human ventricular CFs were used in this study. The differentiation of CFs into myofibroblast was induced with TGF-β and was identified by the expression of smooth muscle actin.

Results: Results indicate that Ca2+ signaling was an essential component of ventricular CF dif­ferentiation. CFs treated with TGF-β demonstrated increased expression of a TRP channel, TRPV4, both at the mRNA and protein levels, which corresponded with CF-myofibroblast trans-differentiation, as evidenced by the upregulation of α-smooth muscle actin, a myofibroblast marker, and plasminogen activator inhibitor-1, which are fibrogenesis markers. An agonist of TRPV4 induced the conversion of CFs into myofibroblasts, whereas it’s antagonist as well a Ca2+ chelating agent reduced it, indicating that the Ca2+ influx throughTRPV4 is required for CF trans-differentiation. Overall, these results dem­onstrate that TRPV4-mediated Ca2+ influx participates in regulating the differentiation of human ventricular CFs into myofibroblasts through the MAPK/ERK pathway.

Conclusions: Overall, these results demonstrate that TRPV4-mediated Ca2+ influx participates in regulating the differentiation of human ventricular CFs into myofibroblasts through the MAPK/ERK pathway.

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Keywords

fibroblast, myofibroblast, transient receptor potential channels, calcium

About this article
Title

Transient receptor potential channel TRPV4 mediates TGF-β1-induced differentiation of human ventricular fibroblasts

Journal

Cardiology Journal

Issue

Vol 27, No 2 (2020)

Pages

162-170

Published online

2019-05-13

DOI

10.5603/CJ.a2019.0050

Pubmed

32329036

Bibliographic record

Cardiol J 2020;27(2):162-170.

Keywords

fibroblast
myofibroblast
transient receptor potential channels
calcium

Authors

Min-Soo Ahn
Young Woo Eom
Ji-Eun Oh
Seung-Kuy Cha
Kyu Sang Park
Jung-Woo Son
Jun-Won Lee
Young Jin Youn
Sung Gyun Ahn
Jang-Young Kim
Seung-Hwan Lee
Junghan Yoon
Byung-Su Yoo

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