Suppressor of cytokine signaling 1-modulated metalloproteinases and tissue inhibitor of metalloproteinase in pulmonary fibrosis

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Publisher： Spandidos Publications

E-ISSN： 1791-3004|12|3|3855-3861

ISSN： 1791-2997

Source： Molecular Medicine Reports, Vol.12, Iss.3, 2015-01, pp. : 3855-3861

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Abstract

An imbalance between metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) affects the synthesis and degradation of extracellular matrix molecules, which have an important role in the pathogenesis of pulmonary fibrosis. Lower mRNA expression levels of suppressor of cytokine signaling 1 (SOCS1) are present in fibroblasts from the lungs of pulmonary fibrosis. However, little is currently known regarding the precise role of SOCS1 has in idiopathic pulmonary fibrosis (IPF). The present study examined the expression levels of MMPs and TIMPs in A549 human epithelial lung carcinoma cells and human embryonic lung fibroblasts (HLFs) stimulated with transforming growth factorβ1 (TGFβ1) in conditions of deficiency and overexpression of SOCS1, by transfection with a lentivirus. Overexpression of SOCS1 in A549 cells and HLFs significantly inhibited the mRNA expression levels of MMP1, MMP2 and MMP9 (P<0.05). In the A549 cells lacking SOCS1 expression, the mRNA expression levels of TIMP1 were significantly higher compared with the control groups (P<0.01). Overexpression of SOCS1 partially reversed these changes. The expression levels of TIMP1 in the HLFs with an overexpression of SOCS1 were decreased, as compared with the SOCS1deficient HLFs following TGFβ1 stimulation; however, this finding was not significant (0.24±0.01 vs. 0.53±0.02, P>0.05). The expression levels of TIMP2 were significantly lower in the cells overexpressing SOCS1. Conversely, the mRNA expression levels of TIMP2 were significantly higher in the SOCS1deficient A549 cells, as compared with all of the other groups (P<0.05). TIMP4 expression levels were elevated in the A549 cells and HLFs transfected with the SOCS1deficient lentivirus. The expression levels of TIMP4 were significantly lower in the groups overexpressing SOCS1, as compared with the other groups. These results suggest that SOCS1 may act as a suppressor of pulmonary fibrosis, by reducing the expression of MMPs and TIMPs. Therefore, SOCS1 may be a target for IPF treatment.