Triphenyl phosphate reduces oxidative muscle-fiber phenotype involving IL-17A-p38 MAPK-PGC1-α signaling pathway

Triphenyl phosphate (TPHP) is widely used in various fields. In recent years, the potential health hazards of this pollutant have attracted great attention from people. However, the impact and potential mechanisms of TPHP on skeletal muscle function still need to be studied.

This study included in vivo animal and in vitro cell experiments. Thirty C57BL/6J mice were randomly assigned to CON, T25, and T50 groups and received an 8-week TPHP gavage treatment. Gastrocnemius tissues were collected for transcriptome sequencing, qPCR, Western blotting (WB), and immunofluorescence (IF) analyses. In vitro, C2C12 myoblasts were exposed to gradient TPHP concentrations for 24 h and subjected to identical molecular detections.

This study showed that after intervention with TPHP, muscle atrophy markers increased in the gastrocnemius muscle of mice, while the expression of genes and proteins related to oxidative muscle fibers decreased. Gene sequencing results showed a significant enrichment of the IL-17A pathway. Cell experiments also showed that after TPHP intervention, the expression of genes and proteins related to muscle atrophy increased in cells, while the expression of genes and proteins related to oxidative muscle fibers decreased. By using relevant inhibitors, we further validated that the IL-17A-p38 MAPK-PGC1-α pathway can reduce oxidative muscle-fiber phenotype regulated by TPHP.

Our research findings indicate that TPHP may reduce oxidative muscle-fiber phenotype involving the IL-17A-p38 MAPK-PGC1-α signaling pathway.