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Hydrostatic pressure suppresses fibrotic changes via Akt/GSK-3 signaling in human cardiac fibroblasts
- Source :
- Physiological Reports
- Publication Year :
- 2018
- Publisher :
- Wiley, 2018.
-
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.
- Subjects :
- 0301 basic medicine
Physiology
Cardiac fibrosis
Hydrostatic pressure
030204 cardiovascular system & hematology
Signalling Pathways
Glycogen Synthase Kinase 3
03 medical and health sciences
0302 clinical medicine
Stress, Physiological
Fibrosis
GSK-3
Physiology (medical)
Akt signaling
Hydrostatic Pressure
medicine
Humans
Phosphorylation
Myofibroblasts
Protein kinase B
cardiac fibroblasts
Cells, Cultured
PI3K/AKT/mTOR pathway
Original Research
Extracellular Matrix Proteins
Chemistry
Heart
Cell Differentiation
medicine.disease
Cell biology
Oncogene Protein v-akt
030104 developmental biology
Inflammation Mediators
Myofibroblast
Signal Transduction
Subjects
Details
- ISSN :
- 2051817X
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Physiological Reports
- Accession number :
- edsair.doi.dedup.....2a44bb495446d0fd03258a3d095db0b1