Modulation Of HOXA9 After Skeletal Muscle Denervation And Reinnervation

Objective:To investigate the mechanism of HOXA9 in skeletal muscles after peripheral nerve injury and reinnervation.Methods:We performed detailed time-dependent expression analyses of HOXA9 and its promoters,MLL1 and WDR5,in rat gastrocnemius muscles after three types of sciatic nerve surgeries: nerve transection(denervation),end-to-end repair(repair),and sham operation(sham).Then,the specific mechanisms of Hoxa9 were detected in vitro by transfecting primary satellite cells with empty pIRES2-DsRed2,pIRES2-DsRed2-HOXA9,empty pPLK/GFP-Puro,and pPLK/GFP-Puro-HOXA9 small hairpin RNA(shRNA)plasmids.Results:We found,for the first time,that HOXA9 protein expression simultaneously increased with increasing denervated muscle atrophy severity,and that upregulated MLL1 and WDR5 expression was partly associated with denervation.Indeed,in vitro experiments revealed that HOXA9 inhibited myogenic differentiation,affected the best known atrophic signaling pathways,and promoted apoptosis but did not eliminate the differentiation potential of primary satellite cells.Conclusion:HOXA9 may promote denervated muscle atrophy by regulating the activity of satellite cells.