Inhibition Effect Of Ac-SDKP On Myofibroblast Differentiation Via CAMP/Epac Signal In Lung Silicosis Induced By Angâ…¡

Objectives To explore the inhibition effect of N-acetyl-seryl-aspartyl-lysyl-proline（Ac-SDKP）on myofibroblast differentiation via cAMP/Epac signal in silicotic lungfibrosis and in MRC-5human fetal lung fibroblasts induced by angiotensin（Ang）II.Methods SiO2powders were douched in the trachea of rat to make the silicotic model and treatedwith Ac-SDKP in post-or pre-manner. The pathological morphous was observed by HE andMasson staining. The protein expression of collagen type I（Col I）, α-SMA, serumresponse factor（SRF）, myocardin-related transcription factor（MRTF）-A, exchangeprotein directly activated by cAMP （Epac）1and β2adrenergic receptor（ADRB2）in lung tissues were measure by western blot. MRC-5human fetal lung fibroblasts wereinduced to myofibroblast by Ang II, and pretreatment with Ac-SDKP or8-Me-cAMP. α-SMA and SRF expression were observed by immnocytochemical stain. The proteinexpression of Cole I, α-SMA, SRF, MRTF-A, Epac1,2were measured by Westen blot.Statistical analysis was performed using statistical software SPSS13.0. P<0.05explainsthat the differences have Statistically significance.Results Ac-SDKP treatment shown a anti-fibrotic effect in vivo and strongly attenuated1）silicosis-induced increased expressions of collagen deposition,2） myofibroblastdifferentiation as indicated by a robust decrease of SRF, MRTF-A and α-SMA-positivemyofibroblast localization in siliconic nodules in the lung,3）up regulation of ADRB2and Epac1. Myofibroblast differentiation could be induced by Ang II from MRC-5cellswith a dose-and time-dependent manner. The up-regulation of SRF and MRTF-A wereobserved in MRC-5cells induced by Ang II and accompanied with collagen I and α-SMA increased by3.4,3.5,3.3and6.8folds, respectively. Pre-treatment with8-Me-cAMP or Ac-SDKP could attenuated all this changes induced by Ang II, and promotedthe expression of Epac1.Conclusion Ac-SDKP can inhibit the myofibroblast differentiation via cAMP/Epac1signal in silicotic lung fibrosis and in MRC-5cells induced by Ang II.