The Role Of TGF-β₁/P38MAPK Signaling Pathway In The Process Of Skeletal Muscle Fibrosis In A Chronic Sciatic Nerve Compression Rat Model

Objective:To investigate the role of TGF-β1/p38MAPK signaling pathway in the process of skeletal muscle fibrosis during the chronically compressed sciatic nerve injury.Methods:A chronic nerve compression (CNC) model was established by placing a cuff on the right sciatic nerve. Those rats were administered saline, SB203580(a specific p38MAPK inhibitor),1D11(a TGF-p inhibitor) or Recombinant Human TGF-β1(rhTGF-β1) daily after the surgery. Electrophysiological characteristics, degree of skeletal muscle fibrosis and messenger RNA (mRNA) levels for TGF-Pi, p38and CTGF were studied at different time points after CNC injury. Meanwhile,the expressions of TGF-β1, P-p38, total p38and CTGF proteins in skeletal muscle were measured by immunofluorescence and Western blot.The results:CNC injury resulted in decreased nerve conduction velocity, amplitude and increased skeletal muscle fibrosis and induced an increase in CTGF and P-p38in the gastrocnemius muscle. SB203580ameliorated skeletal muscle fibrosis and reduced the expressions of CTGF and P-p38caused by CNC injury. The effects of attenuating skeletal muscle fibrosis and reducing the levels of P-p38and CTGF were greater when administration with1D11. However, CNC-induced skeletal muscle fibrosis and increase in P-p38and CTGF were aggravated when treatment with rhTGF-β1. Nerve conduction velocity, amplitude and the expression levels of TGF-β1and p38were not influenced by SB203580,1D11or rhTGF-β1alone. Conclusions:TGF-β1/p38MAPK signaling pathway was involved in the process of skeletal muscle fibrosis during the chronically compressed sciatic nerve injury, p38inhibitor or TGF-β1inhibitor ameliorated fibrosis in the gastrocnemius muscle after chronic sciatic nerve compression.