Long non-coding RNA MFAT1 promotes skeletal muscle fibrosis by modulating the miR-135a-5p-Tgfbr2/Smad4 axis as a ceRNA.
Lin J., Yang X., Liu S., Luo Z., Chen Q., Sun Y., Ding Z., Chen J.
Fibrosis after skeletal muscle injury is common in sports and can cause irreversible damage to the biomechanical properties of skeletal muscle. Long non-coding RNAs (lncRNAs) have been validated to act as important modulators in the fibrosis of various organs. Here, we reported a novel lncRNA (the skeletal muscle fibrosis-associated transcript 1, lnc-MFAT1), which was highly expressed in skeletal muscle fibrosis. We demonstrate that lnc-MFAT1 knockdown can reduce TGFβ-induced fibrosis in vitro and attenuate skeletal muscle fibrosis after acute contusion in mice. Further study showed that lnc-MFAT1 acted as a competitive endogenous RNA of miR-135a-5p. Besides, the miR-135a-5p inhibition obviously promoted TGFβ-induced fibrosis in vitro via enhancing its target genes Tgfbr2/Smad4. Moreover, we discovered that lnc-MFAT1 regulates Tgfbr2/Smad4 expression by sponging miR-135a-5p to exert competing endogenous RNA function, resulting in TGFβ pathway activation. In conclusion, our study identified a crucial role of lnc-MFAT1-miR-135a-Tgfbr2/Smad4 axis in skeletal muscle fibrosis, providing a promising treatment option against skeletal muscle fibrosis.