05 February 2020 : Laboratory Research
Necrostatin-1 Alleviates Bleomycin-Induced Pulmonary Fibrosis and Extracellular Matrix Expression in Interstitial Pulmonary Fibrosis
Fanghong Mou1BCDEF, Canglang Mou2AF*DOI: 10.12659/MSM.919739
Med Sci Monit 2020; 26:e919739
Abstract
BACKGROUND: Interstitial pulmonary fibrosis (IPF) is harmful for patients’ life and health. The effective treatment of IPF is lacking because of unclear pathogenesis. Necrostatin-1 has protective effects on lung injury and can suppress the fibrosis development. I this study we investigated whether necrostatin-1 could decrease the proliferation of pulmonary fibroblasts, pulmonary fibrosis and expression of extracellular matrix (ECM) in IPF.
MATERIAL AND METHODS: The IPF mice model was conducted by intra-tracheal injection of bleomycin (BLM) (2 mg/kg) for C57BL/6N mice. Necrostatin-1 treatment was performed with 1 mg/kg necrostatin-1 by an intravenous injection for C57BL/6N mice. Lung tissue structures and collagen deposition were observed by hematoxylin and eosin staining and Masson staining. IPF in vitro model was constructed by MRC-5 cells induced by transforming growth factor beta 1 (TGF-β1). And, 20 μM necrostatin-1 was used to treat the TGF-β1 induced MRC-5 cells. Cell Counting Kit-8 (CCK-8) assay detected the viability of MRC-5 cells. The expression of receptor-interacting protein kinase-1 and -3 (RIPK1 and RIPK3), α smooth muscle actin (α-SMA), collagen IV, collagen I, fibronectin (FN), and transforming growth factor-β (TGF-β) in lung tissues and MRC-5 cells was measured by western blot analysis. The α-SMA expression in lung tissues was also analyzed by immunohistochemistry.
RESULTS: The expression of RIPK1 and RIPK3 in lung tissues of BLM induced mice was increased. The degree of pulmonary fibrosis and expression of α-SMA, collagen IV, collagen I, FN, and TGF-β in lung tissues of BLM induced mice was enhanced. The proliferation of MRC-5 cells was increased when MRC-5 cells were induced by TGF-β. The expression of RIPK1, RIPK3, α-SMA, collagen IV, collagen I, and FN was increased in TGF-β induced MRC-5 cells. And, necrostatin-1 could effectively reverse the changes of pulmonary fibrosis, RIPK1, RIPK3, and ECM in vivo and in vitro experiments.
CONCLUSIONS: Necrostatin-1 attenuated pulmonary fibrosis in lung tissues of BLM induced mice and inhibited the fibroblast proliferation. And, necrostatin-1 also decreased the expression of RIPK1, RIPK3, and ECM in lung tissues of BLM induced mice and TGF-β induced fibroblasts. Necrostatin-1 could be a new effective drug for the treatment of IPF.
Keywords: Bleomycin, Extracellular Matrix, Pulmonary Fibrosis, Cell Line, Collagen, Fibroblasts, Indoles, Lung, Lung Diseases, Interstitial, Transforming Growth Factor beta1
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