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Transient receptor potential channel TRPV4 mediates TGF-β1-induced differentiation of human ventricular fibroblasts
- Source :
- Cardiol J
- Publication Year :
- 2020
- Publisher :
- Via Medica, 2020.
-
Abstract
- Background: Cardiac fibroblasts (CFs) are principal extracellular matrix-producing cells. In response to injury, CFs transdifferentiate into myofibroblasts. Intracellular calcium (Ca 2+ ) 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 Ca 2+ 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 Ca 2+ chelating agent reduced it, indicating that the Ca 2+ influx throughTRPV4 is required for CF trans-differentiation. Overall, these results dem­onstrate that TRPV4-mediated Ca 2+ 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 Ca 2+ influx participates in regulating the differentiation of human ventricular CFs into myofibroblasts through the MAPK/ERK pathway.
- Subjects :
- MAPK/ERK pathway
TRPV4
musculoskeletal diseases
medicine.medical_specialty
medicine.medical_treatment
Heart Ventricles
TRPV Cation Channels
030204 cardiovascular system & hematology
Calcium in biology
Basic Science and Experimental Cardiology
Transforming Growth Factor beta1
03 medical and health sciences
Transient receptor potential channel
0302 clinical medicine
Downregulation and upregulation
Internal medicine
medicine
Humans
Calcium Signaling
Extracellular Signal-Regulated MAP Kinases
Myofibroblasts
Cells, Cultured
business.industry
Growth factor
virus diseases
General Medicine
Actins
Cell biology
Cell Transdifferentiation
Cardiology
Cardiology and Cardiovascular Medicine
business
Myofibroblast
Transforming growth factor
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Cardiol J
- Accession number :
- edsair.doi.dedup.....36900beb061dd66bdc3af575e6948dae