Porcine transient receptor potential channel 1 (TRPC1) regulates muscle growth via the Wnt/ß-catenin and Wnt/Ca2+ pathways.

ABSTRACT

Transient receptor potential canonical (TRPC) channels allow the intracellular entry of Ca2+ and play important roles in several physio-pathological processes. In this study, we constructed transgenic mice expressing porcine TRPC1 (Tg-pTRPC1) to verify the effects of TRPC1 on skeletal muscle growth and elucidate the underlying mechanism. Porcine TRPC1 increased the muscle mass, fiber cross-sectional area, and exercise endurance of mice and accelerated muscle repair and regeneration. TRPC1 overexpression enhanced ß-catenin expression and promoted myogenesis, which was partly reversed by inhibitors of ß-catenin. TRPC1 facilitated the accumulation of intracellular Ca2+ and nuclear translocation of the NFATC2/NFATC2IP complex involved in the Wnt/Ca2+ pathway, promoting muscle growth. Paired related homeobox 1 (Prrx1) promoted the expression of TRPC1, NFATC2, and NFATC2IP that participate in the regulation of muscle growth. Taken together, our findings indicate that porcine TRPC1 promoted by Prrx1 could regulate muscle development through activating the canonical Wnt/ß-catenin and non-canonical Wnt/Ca2+ pathways.