Open AccessHydrostatic pressure suppresses fibrotic changes via Akt/ GSK ‐3 signaling in human cardiac fibroblasts
Author(s) -
Tanaka Ryo,
Umemura Masanari,
Narikawa Masatoshi,
Fujita Takayuki,
Yokoyama Utako,
Ishigami Tomoaki,
Kimura Kazuo,
Tamura Kouichi,
Ishikawa Yoshihiro
Publication year - 2018
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.13687
Subject(s) - medicine , medical school , library science , political science , medical education , computer science
Mechanical stresses play important roles in the process of constructing and modifying heart structure. It has been well established that stretch force acting on cardiac fibroblasts induces fibrosis. However, the effects of compressive force, that is , hydrostatic pressure ( HP ), have not been well elucidated. We thus evaluated the effects of HP using a pressure‐loading apparatus in human cardiac fibroblasts ( HCF s) in vitro. In this study, high HP (200 mmHg) resulted in significant phosphorylation of Akt in HCF s. HP then greatly inhibited glycogen synthase kinase 3 ( GSK ‐3) α , which acts downstream of the PI 3K/Akt pathway. Similarly, HP suppressed m RNA transcription of inflammatory cytokine‐6, collagen I and III , and matrix metalloproteinase 1, compared with an atmospheric pressure condition. Furthermore, HP inhibited collagen matrix production in a three‐dimensional HCF culture. Taken together, high HP suppressed the differentiation of fibroblasts into the myofibroblast phenotype. HP under certain conditions suppressed cardiac fibrosis via Akt/ GSK ‐3 signaling in HCF s. These results might help to elucidate the pathology of some types of heart disease.