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

An imbalance between metalloproteinases (MVPs) 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 (SOCS1l) 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 (HI-Fs) stimulated with transforming growth factor-beta 1 (TGF-beta 1) in conditions of deficiency and over-expression of SOCS1, by transfection with a lentivirus. Overexpression of SOCS1 in A549 cells and HI-Fs significantly inhibited the ri-iRNA expression levels of MMP-1, MMP-2 and MMP-9 (P<0.05). In the A549 cells lacking SOCS1 expression, the mRNA expression levels of TIMP-1 were significantly higher compared with the control groups (P<0.01). Ovcrexpression of SOCS1 partially reversed these Changes. The expression levels of TIMP-1 in the HI,Fs with an overexpression of SOCS1 were decreased, as compared with the SOCS1-deficient HLFs following TGF-beta 1 stimulation; however, this finding was not significant (0.24 +/- 0.01 vs. 0.53 +/- 0.02, P>0.05). The expression levels of TIMP-2 were significantly lower in the cells over-expressing SOCS1. Conversely, the mRNA expression levels of TIMP-2 were significantly higher in the SOCS1-deficient A549 cells, as compared with all of the other groups (P<0.05). TIMP-4 expression levels were elevated in the A549 cells and HI,Fs transfected with the SOCS1 deficient lentivirus. The expression levels of TIMP-4 were significantly lower in the groups ovcrexpressing 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.