Fibro-Adipogenic Progenitor-Derived Pentraxin 3 Promotes Porcine Slow-Twitch Myofiber Formation by Suppressing the TLR4/TGFβ/SMAD2/3 Signaling Pathway

Abstract Skeletal muscle fiber-type composition is a critical factor influencing pork quality. However, the key proteins governing muscle fiber-type transformation remain largely unclear. Here, we define the secreted protein landscape underlying muscle fiber-type transformation regulation by integrating skeletal muscle explant culture with secretome-based proteomics. Furthermore, multiomics analysis identified pentraxin 3 (PTX3) as a key regulator predominantly secreted by fibro-adipogenic progenitors (FAPs), with expression positively correlated with slow myofiber proportion. Functional assays in porcine satellite cells demonstrated that PTX3 promotes slow-twitch myotube formation and enhances mitochondrial function. Mechanistically, PTX3 suppressed the TLR4/TGFβ/SMAD2/3 signaling pathway to promote slow-twitch myotube formation. Collectively, these findings highlight PTX3 as a key regulatory factor linking muscle biochemistry to pork quality, thereby offering novel molecular targets and potential biomarkers for meat quality control and the development of functional meat products in the food sector.