Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 105, Issue -, Pages 841-847Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2018.03.058
Keywords
Lung fibrosis; SMOC2; Bleomycin (BLM); TGF-beta 1; alpha-SMA
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Although the initiation and modulation of lung fibrosis has been widely investigated, the pathogenesis was not well understood. Secreted modular calcium-binding protein 2 (SMOC2) as the secreted protein acidic is enriched in cysteine (SPARC) family of matricellular proteins, which are important in regulating cell-matrix interactions. Here we aimed to calculate the effects and molecular mechanism of SMOC2 on the progression and severity of lung fibrosis in murine bleomycin (BLM)-induced mice. The pulmonary fibrosis was significantly induced by BLM in wild type (WT) C57BL6 mice, as evidenced by the lung sections histology and collagen accumulation using H&E and Masson Trichrome staining. Notably, SMOC2 knockout (SMOC2(-/-)) mice treated with BLM exhibited the decrease in inflammation accompanied by the reduction of neutrophils, macrophages and lymphocytes in bronchoalveolar lavage fluids (BALF). In addition, the levels of inflammation-associated cytokines and chemokines induced by BLM were also decreased in BALF obtained from SMOC2(-/-) mice. Meanwhile, SMOC2(-/-) suppressed the progression of pulmonary fibrosis, as evidenced by the reduction in levels of transforming growth factor-beta 1 (TGF-beta 1), alpha-smooth muscle actin (alpha-SMA), p-SMAD2 and p-SMAD3 in lung tissue samples. Increasing expression of SMOC2 in TGF-beta 1 treated cells were further observed in vitro. Of note, up regulation of SMOC2 activated-fibrosis development in MRC-5 cells, along with increase of alpha-SMA, p-SMAD2 and p-SMAD3 were determined. In contrast, SMOC2 knockdown reduced TGF-beta 1-stimulated expressions of alpha-SMA, p-SMAD2 and p-SMAD3 in cells. The findings above suggested that SMOC2 knockout contributes to inhibit BLM-induced pulmonary fibrosis.
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