Suppression of SMOC2 reduces bleomycin (BLM)-induced pulmonary fibrosis by inhibition of TGF-β1/SMADs pathway.

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-β1 (TGF-β1), α-smooth muscle actin (α-SMA), p-SMAD2 and p-SMAD3 in lung tissue samples. Increasing expression of SMOC2 in TGF-β1 treated cells were further observed in vitro. Of note, up regulation of SMOC2 activated-fibrosis development in MRC-5 cells, along with increase of α-SMA, p-SMAD2 and p-SMAD3 were determined. In contrast, SMOC2 knockdown reduced TGF-β1-stimulated expressions of α-SMA, p-SMAD2 and p-SMAD3 in cells. The findings above suggested that SMOC2 knockout contributes to inhibit BLM-induced pulmonary fibrosis.