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RBM20 Deficiency Postpones Skeletal Muscle Regeneration After Injury and Promotes Fibrotic Tissue Formation
Author(s) -
Rexiati Maimaiti,
Sun Mingming,
Guo Wei
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.769.5
Subject(s) - myod , myogenin , myf5 , myocyte , skeletal muscle , muscle hypertrophy , regeneration (biology) , medicine , endocrinology , biology , anatomy , microbiology and biotechnology , myogenesis
RNA binding motif 20 (RBM20) is a splicing factor with specific expression in striated muscles. It regulates muscle gene splicing and expression. Previous study indicated that RBM20 is associated with myoblast differentiation in C2C12 cell cultures. With higher expression of RBM20, myoblasts were highly differentiated. In this study, we evaluated whether RBM20 regulates muscle differentiation and regeneration in rat muscle injury model. Methods Muscle injury model was made with 9‐week‐old male wild type (WT) and RBM20 knockout (KO) rats by injecting 0.5ml of 1.2% barium chloride into tibialis anterior and normal saline as control. Tibialis anterior muscles are harvested at 18hours, 3days, 5days, 7days, 14days, and 1month post‐injury (n=5 per time point) and used for western blot, histological and immunofluorescence analyses. Results Our results indicated that muscle mass and the regenerating fiber numbers were not significantly different between WT and KO injury during the whole process of regeneration. However, mean cross‐sectional area (CSA) of the regenerating myofibers after 7‐day post injury was significantly smaller in KO when compared to WT, indicating delayed muscle regeneration after injury in RBM20 KO. Further, we found that fibrotic area and TGFβ1 signaling were significantly increased in KO as compared to WT after 14‐day post injury. To test whether RBM20 involves muscle differentiation, we evaluated the expression of Pax7, MyoD, and Myogenin at 5 and 7‐day post injury, we found no changes of these transcription factors at 5 days, but MyoD was significantly reduced at 7 days in KO muscle compared to WT. Interestingly, we found that RBM20 expression was increased with post injury muscle regeneration from 18 hours to 1 month. Conclusion RBM20 is a novel factor that promotes muscle regeneration after injury and protect from fibrotic tissue formation. Support or Funding Information This work was supported by the NIFA‐USDA 1009266, National Institutes of Health NIGMSP20GM103432, AHA BGIA and Faculty‐Grant‐in‐Aid from University of Wyoming. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .