State Key Laboratory of animal biotech breeding, Beijing Key Laboratory of animal genetic engineering, China Agricultural University, Beijing 100193, China.
State Key Laboratory of animal biotech breeding, Beijing Key Laboratory of animal genetic engineering, China Agricultural University, Beijing 100193, China; Sanya Institute of China Agricultural University, Sanya, Hainan 572025, China.
Int J Biol Macromol. 2024 Apr;265(Pt 1):130855. doi: 10.1016/j.ijbiomac.2024.130855. Epub 2024 Mar 13.
Transient receptor potential canonical (TRPC) channels allow the intracellular entry of Ca 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 β-catenin expression and promoted myogenesis, which was partly reversed by inhibitors of β-catenin. TRPC1 facilitated the accumulation of intracellular Ca and nuclear translocation of the NFATC2/NFATC2IP complex involved in the Wnt/Ca 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/β-catenin and non-canonical Wnt/Ca pathways.
瞬时受体电位经典型 (TRPC) 通道允许细胞内 Ca 的进入，并在几种生理病理过程中发挥重要作用。在这项研究中，我们构建了表达猪 TRPC1（Tg-pTRPC1）的转基因小鼠，以验证 TRPC1 对骨骼肌生长的影响，并阐明其潜在机制。猪 TRPC1 增加了小鼠的肌肉质量、纤维横截面积和运动耐力，并加速了肌肉修复和再生。TRPC1 过表达增强了 β-连环蛋白的表达，并促进了成肌作用，而 β-连环蛋白抑制剂部分逆转了这一作用。TRPC1 促进了细胞内 Ca 的积累和参与 Wnt/Ca 通路的 NFATC2/NFATC2IP 复合物的核易位，从而促进肌肉生长。配对相关同源盒蛋白 1 (Prrx1) 促进了参与肌肉生长调节的 TRPC1、NFATC2 和 NFATC2IP 的表达。总之，我们的研究结果表明，Prrx1 促进的猪 TRPC1 可以通过激活经典 Wnt/β-连环蛋白和非经典 Wnt/Ca 通路来调节肌肉发育。
