title: Suppressor of cytokine signaling 1-modulated metalloproteinases and tissue inhibitor of metalloproteinase in pulmonary fibrosis.
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 factor‑β1 (TGF‑β1) in conditions of deficiency and over‑expression of SOCS1, by transfection with a lentivirus. Overexpression of SOCS1 in A549 cells and HLFs significantly inhibited the mRNA 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). Overexpression of SOCS1 partially reversed these changes. The expression levels of TIMP‑1 in the HLFs with an overexpression of SOCS1 were decreased, as compared with the SOCS1‑deficient HLFs following TGF‑β1 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 overexpressing 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 HLFs transfected with the SOCS1‑deficient lentivirus. The expression levels of TIMP‑4 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.
authors.affiliation: Department of Respiratory Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, P.R. China.
authors.forename: Qiurui
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Respiratory Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, P.R. China.
authors.forename: Ran
authors.initials: R
authors.lastname: Dong
authors.affiliation: Department of Respiratory Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, P.R. China.
authors.forename: Ranran
authors.initials: R
authors.lastname: Dai
authors.affiliation: Department of Respiratory Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
mesh_terms: D045744:Cell Line, Tumor; D015870:Gene Expression; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000201:enzymology*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000502:physiology*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism; D000097792:Tissue Inhibitor of Metalloproteinase-4
chemical_list: D020781:Matrix Metalloproteinase 1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D019716:Tissue Inhibitor of Metalloproteinase-2; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4; C108944:SOCS1 protein, human; C560823:TIMP2 protein, human; C522361:MMP2 protein, human; C579270:MMP9 protein, human; C522360:MMP1 protein, human