Effect of hypoxia-inducible factor 1 alpha inhibitor on immobilization-induced muscle fibrosis related to muscle contracture

Abstract

[Purpose] To test the effect of the hypoxia-inducible factor 1-alpha (HIF-1α) inhibitor, YC-1, on the upregulation of HIF-1α that leads to immobilization-induced muscle fibrosis underlying muscle contracture. [Materials and Methods] Rats were divided into control, immobilization (immobilization only), and YC-1 (immobilization and YC-1 injection) groups. The soleus muscles were the specimens. [Results] The HIF-1α protein expression in the control, immobilization, and YC-1 groups was 0.26 ± 0.11, 0.94 ± 0.28, and 0.66 ± 0.15, respectively. The expression of HIF-1α protein in the immobilization and YC-1 groups was significantly higher than in the control group and it was lower in the YC-1 group than in the immobilization group. There were strong positive correlations between HIF-1α protein expression and transforming growth factor (TGF)-β1 mRNA expression, TGF-β1 and α-smooth muscle actin (SMA) mRNA expressions, and between α-SMA mRNA expression and hydroxyproline content. A strong negative correlation was found between hydroxyproline content and range of motion on dorsiflexion at four-weeks. [Conclusion] Inhibition of HIF-1α may contribute to suppressing the overexpression of fibrosis-related molecules triggered by upregulation of HIF-1α, which may mitigate immobilization-induced muscle fibrosis related to muscle contracture.