Piezo1 Mechanosensitive Ion Channel Mediates Stretch-Induced Nppb Expression in Adult Rat Cardiac Fibroblasts

In response to stretch, cardiac tissue produces natriuretic peptides, which have been suggested to have beneficial effects in heart failure patients. In the present study, we explored the mechanism of stretch-induced brain natriuretic peptide (Nppb) expression in cardiac fibroblasts. Primary adult r...

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Main Authors: Meike C. Ploeg, Chantal Munts, Frits W. Prinzen, Neil A. Turner, Marc van Bilsen, Frans A. van Nieuwenhoven
Format: Article
Language:English
Published: MDPI AG 2021-07-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/10/7/1745
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author Meike C. Ploeg
Chantal Munts
Frits W. Prinzen
Neil A. Turner
Marc van Bilsen
Frans A. van Nieuwenhoven
author_facet Meike C. Ploeg
Chantal Munts
Frits W. Prinzen
Neil A. Turner
Marc van Bilsen
Frans A. van Nieuwenhoven
author_sort Meike C. Ploeg
collection DOAJ
description In response to stretch, cardiac tissue produces natriuretic peptides, which have been suggested to have beneficial effects in heart failure patients. In the present study, we explored the mechanism of stretch-induced brain natriuretic peptide (Nppb) expression in cardiac fibroblasts. Primary adult rat cardiac fibroblasts subjected to 4 h or 24 h of cyclic stretch (10% 1 Hz) showed a 6.6-fold or 3.2-fold (<i>p</i> < 0.05) increased mRNA expression of Nppb, as well as induction of genes related to myofibroblast differentiation. Moreover, BNP protein secretion was upregulated 5.3-fold in stretched cardiac fibroblasts. Recombinant BNP inhibited TGFβ1-induced Acta2 expression. Nppb expression was >20-fold higher in cardiomyocytes than in cardiac fibroblasts, indicating that cardiac fibroblasts were not the main source of Nppb in the healthy heart. Yoda1, an agonist of the Piezo1 mechanosensitive ion channel, increased Nppb expression 2.1-fold (<i>p</i> < 0.05) and significantly induced other extracellular matrix (ECM) remodeling genes. Silencing of Piezo1 reduced the stretch-induced Nppb and Tgfb1 expression in cardiac fibroblasts. In conclusion, our study identifies Piezo1 as mediator of stretch-induced Nppb expression, as well as other remodeling genes, in cardiac fibroblasts.
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spelling doaj.art-a146ad4ad4db43d7a2d8ac62bf36e1662023-11-22T03:29:23ZengMDPI AGCells2073-44092021-07-01107174510.3390/cells10071745Piezo1 Mechanosensitive Ion Channel Mediates Stretch-Induced Nppb Expression in Adult Rat Cardiac FibroblastsMeike C. Ploeg0Chantal Munts1Frits W. Prinzen2Neil A. Turner3Marc van Bilsen4Frans A. van Nieuwenhoven5Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6200 MD Maastricht, The NetherlandsDepartment of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6200 MD Maastricht, The NetherlandsDepartment of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6200 MD Maastricht, The NetherlandsDiscovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds LS2 9JT, UKDepartment of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6200 MD Maastricht, The NetherlandsDepartment of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6200 MD Maastricht, The NetherlandsIn response to stretch, cardiac tissue produces natriuretic peptides, which have been suggested to have beneficial effects in heart failure patients. In the present study, we explored the mechanism of stretch-induced brain natriuretic peptide (Nppb) expression in cardiac fibroblasts. Primary adult rat cardiac fibroblasts subjected to 4 h or 24 h of cyclic stretch (10% 1 Hz) showed a 6.6-fold or 3.2-fold (<i>p</i> < 0.05) increased mRNA expression of Nppb, as well as induction of genes related to myofibroblast differentiation. Moreover, BNP protein secretion was upregulated 5.3-fold in stretched cardiac fibroblasts. Recombinant BNP inhibited TGFβ1-induced Acta2 expression. Nppb expression was >20-fold higher in cardiomyocytes than in cardiac fibroblasts, indicating that cardiac fibroblasts were not the main source of Nppb in the healthy heart. Yoda1, an agonist of the Piezo1 mechanosensitive ion channel, increased Nppb expression 2.1-fold (<i>p</i> < 0.05) and significantly induced other extracellular matrix (ECM) remodeling genes. Silencing of Piezo1 reduced the stretch-induced Nppb and Tgfb1 expression in cardiac fibroblasts. In conclusion, our study identifies Piezo1 as mediator of stretch-induced Nppb expression, as well as other remodeling genes, in cardiac fibroblasts.https://www.mdpi.com/2073-4409/10/7/1745mechanosensingcardiac fibroblastbrain natriuretic peptidepiezo1stretch
spellingShingle Meike C. Ploeg
Chantal Munts
Frits W. Prinzen
Neil A. Turner
Marc van Bilsen
Frans A. van Nieuwenhoven
Piezo1 Mechanosensitive Ion Channel Mediates Stretch-Induced Nppb Expression in Adult Rat Cardiac Fibroblasts
Cells
mechanosensing
cardiac fibroblast
brain natriuretic peptide
piezo1
stretch
title Piezo1 Mechanosensitive Ion Channel Mediates Stretch-Induced Nppb Expression in Adult Rat Cardiac Fibroblasts
title_full Piezo1 Mechanosensitive Ion Channel Mediates Stretch-Induced Nppb Expression in Adult Rat Cardiac Fibroblasts
title_fullStr Piezo1 Mechanosensitive Ion Channel Mediates Stretch-Induced Nppb Expression in Adult Rat Cardiac Fibroblasts
title_full_unstemmed Piezo1 Mechanosensitive Ion Channel Mediates Stretch-Induced Nppb Expression in Adult Rat Cardiac Fibroblasts
title_short Piezo1 Mechanosensitive Ion Channel Mediates Stretch-Induced Nppb Expression in Adult Rat Cardiac Fibroblasts
title_sort piezo1 mechanosensitive ion channel mediates stretch induced nppb expression in adult rat cardiac fibroblasts
topic mechanosensing
cardiac fibroblast
brain natriuretic peptide
piezo1
stretch
url https://www.mdpi.com/2073-4409/10/7/1745
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