Role of extracellular signal-regulated kinase 1/2 on inhibition of N-acetyl-seryl-aspartyl-lysyl-proline on proliferation and collagen synthesis of cultured rat pulmonary fibroblasts induced by platelet-derived growth factor / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the role of extracellular signal-regulated kinase 1/2 on the inhibition of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) on the proliferation and collagen synthesis of cultured rat pulmonary fibroblasts induced by platelet-derived growth factor (PDGF).</p><p><b>METHODS</b>Pulmonary fibroblasts were prepared from lungs of neonatal Wistar rats as described previously. Cells were divided into 4 groups: (1) control group (0.4% FBS group); (2) PDGF (10 ng/ml) stimulated group; (3) PD98059+PDGF group (25 micromol/L PD98059+10 ng/ml PDGF); (4) AcSDKP+PDGF group (10(-8) mol/L AcSDKP+10 ng/ml PDGF). All experiments were performed in the fourth passages. Metabolic activity of fibroblasts was observed by MTT, and expressions of type I and type III collagen were measured by immunocytochemistry and western blot. Expressions of phospho-ERK1/2 and ERK1/2 were detected by western blot.</p><p><b>RESULTS</b>Compared with control group, exposure of pulmonary fibroblasts to 10 ng/ml PDGF increased cell metabolic activity, expression of type I and type III collagen and phosphorylation of ERK1/2. 25 micromol/L PD98059 and AcSDKP both could inhibit the metabolic activity of pulmonary fibroblasts, type I and type III collagen synthesis and phosphorylation of ERK1/ 2 induced by PDGF, with significant differences (P < 0.05). AcSDKP+PDGF group compared with PDGF stimulated group, metabolic activity of pulmonary fibroblasts decreased to 77.4%. Immunocytochemistry result showed that in AcSDKP+PDGF group, expressions of type I and type III collagen decreased to 69.3% and 67.2% compared with those of PDGF stimulated group. Western blot result showed that in AcSDKP+PDGF group, expressions of type I and type III collagen decreased to 92.4% and 78.0%, phospho-ERK1/2 decreased to 83.5% compared with those of PDGF stimulated group, with significant differences (P < 0.05).</p><p><b>CONCLUSION</b>ERK1/2 plays an important role in the inhibition of AcSDKP on the proliferation and collagen synthesis of cultured rat pulmonary fibroblasts induced by PDGF.</p>

Antifibrotic effects of N-acetyl-seryl-aspartyl-lysyl-proline mediated by regulation of transforming growth factor beta and connective tissue growth factor expression on rats with silicosis / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate whether the effect of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) on transforming growth factor beta (TGF-beta1) and connective tissues growth factor (CTGF) was involved in AcSDKP's antifibrotic effect on the rats with silicosis.</p><p><b>METHODS</b>Rats were divided into 6 groups randomly, 10 rats in each group: Control of silicotic model: 1.0 ml normal sodium and was killed after 4 or 8 weeks; Silicotic model 1: 50 mg/ml silica suspension and was killed after 4 weeks; Silicotic model 2: 50 mg/ml silica suspension and was killed after 8 weeks; Anti-fibrosis treatment of AcSDKP: after each rat was intratracheally instilled with 50 mg/ml silica suspension for 4 weeks, AcSDKP 800 microg/(kg x d) was administered into every rat and rats were killed at the 8 weeks; Preventing fibrosis treatment of AcSDKP: after AcSDKP [800 microg/(kg x d)] was administered into every rat for 48 hours, each rat was intratracheally instilled with 50 mg/ml silica suspension and rats were killed at the 8 weeks. Lung fibrosis in morphology was observed by HE staining. The expressions of TGF-beta1 and CTGF in lung were observed by immunohistochemistry. The mRNA expressions of TGF-beta1 and CTGF in lung were observed by real-time PCR.</p><p><b>RESULTS</b>In anti-fibrosis treatment of AcSDKP group, protein expression of TGF-beta1 and CTGF were (0.244 +/- 0.016) and (0.241 +/- 0.017) respectively, and significantly lower that those in the silicotic model 1 and 2 groups; mRNA expressions of TGF-beta1 and CTGF decreased, mRNA expressions of CTGF were significantly lower that those in the silicotic model 1 and 2 groups (P < 0.05); In preventing fibrosis treatment of AcSDKP group, protein expression and mRNA expression of TGF-beta1 were significantly lower that those in the silicotic model 2 group (P < 0.05).</p><p><b>CONCLUSION</b>AcSDKP can decrease the expressions of TGF-beta1 and CTGF in lung tissues of the rats with experimentally induced pulmonary fibrosis.</p>