RESUMO
Nacetylserylaspartyllysylproline (AcSDKP) is a natural tetrapeptide that is released from thymosin ß4 by prolyl oligopeptides. It is hydrolyzed by the key enzyme of the reninangiotensin system, angiotensinconverting enzyme (ACE). The aim of the present study was to investigate the alterations in AcSDKP and the ACE/angiotensin II (Ang II)/angiotensin II type 1 (AT1) receptor axis and its impact on the pathogenesis and development of silicotic fibrosis. For in vivo studies, a HOPE MED 8050 exposure control apparatus was used to establish different stages of silicosis in a rat model treated with AcSDKP. For in vitro studies, cultured primary lung fibroblasts were induced to differentiate into myofibroblasts by Ang II, and were pretreated with AcSDKP and valsartan. The results of the present study revealed that, during silicosis development, ACE/Ang II/AT1 expression in local lung tissues increased, whereas that of AcSDKP decreased. AcSDKP and the ACE/AT1/Ang II axis were inversely altered in the development of silicotic fibrosis. AcSDKP treatment had an antifibrotic effect in vivo. Compared with the silicosis group, the expression of αsmooth muscle actin (αSMA), Collagen (Col) I, Fibronectin (Fn) and AT1 were significantly downregulated, whereas matrix metalloproteinase1 (MMP1) expression and the MMP1/tissue inhibitor of metalloproteinases1 (TIMP1) ratio was increased in the AcSDKP treatment group. In vitro, pretreatment with AcSDKP or valsartan attenuated the expression of αSMA, Col I, Fn and AT1 in Ang IIinduced fibroblasts. In addition, MMP1 expression and the MMP1/TIMP1 ratio were significantly higher in AcSDKP and valsartan pretreatment groups compared with the Ang II group. In conclusion, the results of the present study suggest that an imbalance between AcSDKP and ACE/Ang II/AT1 molecules promotes the development of silicosis and that AcSDKP protects against silicotic fibrosis by inhibiting Ang IIinduced myofibroblast differentiation and extracellular matrix production.
