Angiotensin-II Drives Human Satellite Cells Toward Hypertrophy and Myofibroblast Trans-Differentiation by Two Independent Pathways

摘要: Skeletal muscle regeneration is ensured by satellite cells (SC), which upon activation undergo self-renewal and myogenesis. The correct sequence of healing events may be offset inflammatory and/or fibrotic factors able to promote fibrosis consequent wasting. Angiotensin-II (Ang) an effector peptide the renin angiotensin system (RAS), direct role in human SCs (hSCs) still controversial. Based on hypertrophic fibrogenic effects Ang via transient receptor potential canonical (TRPC) channels cardiac renal tissues, we hypothesized a similar axis hSCs. Toward this aim, demonstrated that hSCs respond acute stimulation, dose-dependently enhancing p-mTOR, p-AKT, p-ERK1/2 p-P38. Additionally, sub-acute conditioning increased cell size promoted trans-differentiation into myofibroblasts. To provide mechanistic hypothesis TRPC channel involvement processes, proved mediate basal calcium entry stimulated strongly amplified sub-chronic conditioning. Altogether, these findings demonstrate induces fate shift myofibroblasts basis support benefit RAS blockade oppose fibrosis.