EPAC expression and function in cardiac fibroblasts and myofibroblasts.

Area of Science:

• Cardiovascular Biology
• Cellular Signaling
• Fibrosis Research

Background:

• Cardiac fibroblasts (CF) and myofibroblasts (CMF) are key in cardiac wound healing.
• Exchange protein activated by cAMP (EPAC) is a cAMP effector with uncharacterized roles in CF and CMF.
• Transforming growth factor β1 (TGF-β1) is a critical regulator of cardiac remodeling.

Purpose of the Study:

• To investigate the effect of TGF-β1 on EPAC-1 expression in CF and CMF.
• To determine the role of EPAC in collagen synthesis, adhesion, migration, and collagen gel contraction in CF and CMF.

Main Methods:

• Rat neonatal CF and CMF were treated with TGF-β1.
• EPAC-1 levels and Rap1 activation were measured using western blot and pull-down assays.
• Cellular functions (adhesion, migration, collagen gel contraction, collagen synthesis) were assessed.

Main Results:

• TGF-β1 differentially regulated EPAC-1 expression via distinct signaling pathways (Smad, JNK, ERK1/2, AKT) in CF and CMF.
• EPAC activation increased Rap1-GTP levels, promoting adhesion in both cell types and migration in CF.
• EPAC modulated collagen gel contraction and reduced collagen synthesis in both CF and CMF.

Conclusions:

• TGF-β1 exhibits differential regulation of EPAC expression in CF versus CMF.
• EPAC plays distinct roles in regulating CF and CMF functions critical for cardiac remodeling and wound healing.