Hydrostatic pressure suppresses fibrotic changes via Akt/GSK‐3 signaling in human cardiac fibroblasts. Issue 9 (3rd May 2018)

• Record Type: Journal Article
• Authors: Tanaka, Ryo; Umemura, Masanari; Narikawa, Masatoshi; Fujita, Takayuki; Yokoyama, Utako; Ishigami, Tomoaki; Kimura, Kazuo; Tamura, Kouichi; Ishikawa, Yoshihiro
• Is Part Of: Physiological reports. Volume 6:Issue 9(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-05-03
• Subjects: Akt signaling -- cardiac fibroblasts -- hydrostatic pressure; Physiology -- Periodicals; 571
• DOI: 10.14814/phy2.13687
• Languages: English
• ISSNs: 2051-817X

Abstract

Abstract: 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 (HCFs) in vitro. In this study, high HP (200 mmHg) resulted in significant phosphorylation of Akt in HCFs. HP then greatly inhibited glycogen synthase kinase 3 (GSK‐3) α, which acts downstream of the PI3K/Akt pathway. Similarly, HP suppressed mRNA 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 HCFs. These results might help to elucidate the pathology of some types of heart disease. Abstract : We evaluated the effects of hydorostatic pressure using a pressure‐loading apparatus in human cardiac fibroblasts (HCFs) in vitro. High HP (200 mmHg) resulted in significant change in Akt signaling pathway in HCFs. As a result, high HP suppressed the profibrotic responses such as differentiation of fibroblasts into the myofibroblast phenotype, collagen matrix production.