Circ-sh3rf3/GATA-4/miR-29a regulatory axis in fibroblast-myofibroblast differentiation and myocardial fibrosis

Area of Science:

• Cardiovascular Biology
• Molecular Cardiology
• Epigenetics

Background:

• Cardiac fibrosis involves fibroblast to myofibroblast transdifferentiation, a process not fully understood.
• Circular RNA SH3 domain containing Ring Finger 3 (circ-sh3rf3) is implicated in cardiac hypertrophy but its role in fibrosis is unclear.

Purpose of the Study:

• To investigate the role of circ-sh3rf3 in cardiac fibroblast to myofibroblast differentiation and myocardial fibrosis.
• To elucidate the underlying molecular mechanism of circ-sh3rf3 in regulating cardiac fibrosis.

Main Methods:

• Investigated circ-sh3rf3 expression in isoproterenol-treated rat cardiac fibroblasts and cardiomyocytes.
• Analyzed the interaction between circ-sh3rf3 and GATA-4 proteins.
• Assessed the impact of circ-sh3rf3 on GATA-4 and miR-29a expression.
• Evaluated the effect on fibroblast-myofibroblast differentiation and myocardial fibrosis.

Main Results:

• Circ-sh3rf3 expression was down-regulated in cardiac fibroblasts and cardiomyocytes during differentiation and in response to isoproterenol.
• Circ-sh3rf3 interacts with GATA-4, reducing its expression.
• Reduced GATA-4 expression led to increased miR-29a expression.
• Up-regulation of miR-29a inhibited fibroblast-myofibroblast differentiation and myocardial fibrosis.

Conclusions:

• A novel regulatory cascade, Circ-sh3rf3/GATA-4/miR-29a, controls fibroblast-myofibroblast differentiation and myocardial fibrosis.
• Circ-sh3rf3 acts as a suppressor of cardiac fibrosis.
• This pathway presents a potential therapeutic target for treating myocardial fibrosis.