FKBP10 Silencing Alleviates Gluteal Muscle Contracture by Inhibiting Fibrosis and Restoring Autophagy via HSP47/SMAD3 Pathway Inactivation.

FKBP prolyl isomerase 10 (FKBP10) plays a key role in fibrosis-driven progression of gluteal muscle contracture (GMC). This study investigated the molecular mechanism of FKBP10 in GMC progression. Expression levels of FKBP10, heat shock protein 47 (HSP47), SMAD3, autophagy, and fibrosis-related indicators were analyzed for correlations. The GMC rat model was constructed by injecting methanol penicillin. The interaction between FKBP10 and HSP47 was also assessed. FKBP10 expression was up-regulated in the gluteal muscle of patients with GMC and rats, accompanied by obvious damage and fibrosis. Elevated levels of transforming growth factor beta 1 (TGF-β1), α-smooth muscle actin (α-SMA), collagen I, collagen III, vimentin, fibronectin, p62, and LC3, along with decreased levels of matrix metalloproteinase-9 and LC3II/I, Beclin 1, p62, and ATG7, indicated weakened autophagy. FKBP10 expression correlated negatively with autophagy indicators and positively with HSP47 and fibrosis indicators. FKBP10 interacted with HSP47. Knockdown of FKBP10 down-regulated the levels of HSP47 and phosphorylated SMAD3/SMAD3. Furthermore, knockdown of FKBP10, HSP47, and rapamycin partially reversed the TGF-β1-induced effect. Conversely, 3-methyl adenine and HSP47 overexpression enhanced TGF-β1-induced effects. In GMC rats, FKBP10 knockdown reduced tissue damage and fibrosis, reversed HSP47, phosphorylated SMAD3/SMAD3, fibrosis, and autophagy indicator levels, and reduced autophagy and LC3 levels. In summary, silencing FKBP10 inactivated the HSP47/SMAD3 signaling pathway, inhibited fibrosis, and ameliorated autophagy defects, thereby alleviating GMC.