Myocardin and microRNA-1 modulate bladder activity through connexin 43 expression during post-natal development

Area of Science:

• Urology
• Molecular Biology
• Developmental Biology

Background:

• Overactive bladder (OAB) is a common condition with unclear myogenic mechanisms.
• Understanding smooth muscle cell (SMC) regulation is key to addressing OAB.

Purpose of the Study:

• Investigate the roles of myocardin (MYOCD) and microRNA-1 (miR-1) in bladder myogenic activity.
• Elucidate the regulation of connexin 43 (GJA1) by MYOCD and miR-1 during bladder development.

Main Methods:

• Utilized wild-type (WT) and Myocardin heterozygous-knockout (MYOCD+/-) mouse models.
• Analyzed gene and protein expression of MYOCD, miR-1, and GJA1 in bladder tissues.
• Performed experiments in cultured rat bladder SMC and in vivo bladder models.

Main Results:

• MYOCD down-regulation and decreased SMC contractile genes observed in WT bladders during development.
• MYOCD+/- mice showed reduced Myocd, SMC genes, and bladder SMC hypersensitivity mediated by gap junctions.
• MYOCD suppressed GJA1 expression via miR-1 up-regulation in bladder SMC.

Conclusions:

• MYOCD negatively regulates GJA1 expression through miR-1, impacting bladder smooth muscle function.
• This MYOCD-miR-1-GJA1 axis is vital for normal bladder development, sensitivity, and capacity.