Nur77 Regulates the Phosphorylation of Smad3, Thereby Influencing Skeletal Muscle Fibrosis Caused by Obesity.

Skeletal muscle fibrosis is caused by excessive production or reduced degradation of extracellular matrix, leading to excessive accumulation of collagen. Obesity can trigger physiological and pathological changes in skeletal muscle, such as fibrosis, muscle atrophy, and impaired muscle regeneration. Nerve growth factor-induced gene B (Nur77), a transcription factor encoded by orphan nuclear receptor 4A1 (NR4A1), a member of the immediate early gene nuclear receptor subfamily 4A group, participates in a variety of life activities. Here, we found that in the obese mouse model fed with a high-fat diet, mice with Nur77 gene knockout would exacerbate the skeletal muscle fibrosis phenotype caused by obesity. It is worth noting that Nur77 can bind to the central downstream molecules Smad3, which regulates the synthesis of fibrotic proteins COL1A1 and COL3A1. The activity of the Smad3 protein is crucial for obesity-related muscle fibrosis, suggesting that Nur77 may affect skeletal muscle fibrosis by regulating the activity of Smad3.