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| MAPK pathway mediates the ability of Prx-1 to inhibite myofibroblast transformation in mice with silicosis |
| LIU Yan HONG Fan WANG Peng LI Qian BAI Zhaorong SUN Ying▲ |
| Department of Pathology, School of Basic Medical Science, North China University of Science and Technology, Hebei Province, Tangshan 063210, China |
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Abstract Objective To investigate the role of mitogen-activated protein kinase (MAPK) pathway in the transformation of thioredoxin peroxidase-1 (Prx-1) against myofibroblasts of silicosis. Methods Forty male C57BL/6 mice were randomly divided into control group (saline), model group (SiO2), transfection control group (SiO2 + lentivirus vector) and PRX-1 transfection group (SiO2 + Prx-1 lentivirus). Normal saline, SiO2 and lentivirus were perfused through bronchus. After modeling, mice were fed for 12 weeks. Immunohistochemistry and immunofluorescence were used to detect the expression of α-smooth muscle actin (α-SMA) and 8-hydroxydeoxyguanosine (8-OHdG) respectively. Western blot was used to detect the expression of collagen type Ⅰ, collagen type Ⅲ, Prx-1, phosphorylated extracellular signal-regulated kinase (p-ERK1/2), phosphorylated-mitogen-activated protein kinase p38 (P-p38) and phosphorylated amino-terminal kinase (p-JNK). Results Silicon nodules and pulmonary interstitial fibrosis were found in model group and transfection control group, but the lesions were alleviated in Prx-1 transfection group. There was no difference in Prx-1 expression between model group and transfection control group, but compared with model group, Prx-1 expression increased in Prx-1 transfection group. Compared with control group, the expression of α-SMA, 8-OHdG, collagen type Ⅰ and collagen type Ⅲ, p-ERK1/2, p-P38 and p-JNK were increased in lung tissue of the other groups. Compared with the model group and the transfection control group, the expression of the above indicators in the Prx-1 transfection group were decreased. Conclusion Prx-1 can inhibit SiO2-induced myofibroblast transformation and pulmonary fibrosis, which is related to the reduction of oxygen-active substances and the inhibition of activation of MAPK pathway.
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