Abstract:
Objective To explore the inhibition effect of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) on myofibroblast differentiation via Epac (exchange protein directly activated by cAMP) signal in silicotic rat lung fibrosis and in MRC-5 human fetal lung fibroblasts induced by angiotensin (Ang) Ⅱ.
Methods SiO2 powders were douched in the trachea of rat to establish the silicosis model (four-week and eight-week silicosis groups) and Ac-SDKP were administered in post-(Ac-SDKP intervention group) or pre-manner (Ac-SDKP treatment group).MRC-5 human fetal lung fibroblasts were induced to myofibroblast by Ang Ⅱ,and pre-treated with Ac-SDKP and 8-Me-cAMP (8-pCPT-2'-O-Me-cAMP).The pathological morphologic evidence was observed by HE and Masson staining.The expression of α-smooth muscle actin (α-SMA) was located by immunohistochemistry.The protein expressions of collagen type I (Col I),α-SMA,and Epac were measure by Western blot.
Results Myofibroblast differentiation indicated by α-SMA positivewas observed in silicosis nodules in the silicosis groups.Up-regulated expression of Col I and α-SMA and down-regulated expressionof Epac1 protein were also detected by Western blot assay.Ac-SDKP intervention or treatment showed an anti-fibrotic effect in vivo and strongly attenuated the above induced changes.The positive stain of α-SMA was observed in MRC-5 cells induced by Ang Ⅱ and accompanied with the up-regulation of Col I and α-SMA.Pre-treatment with 8-Me-cAMP or Ac-SDKP promoted expression of Epac1 and attenuated Ang Ⅱ induced up-regulation of Col I and α-SMA.
Conclusion Ac-SDKP could inhibit the myofibroblast differentiation and collagen deposition via Epac signal activation in silicotic rat lung fibrosis and in MRC-5 cells induced by Ang Ⅱgroup
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