Pirfenidone inhibits TGF-β1-induced over-expression of collagen type I and heat shock protein 47 in A549 cells.
Pirfenidone inhibits TGF-β1-induced over-expression of collagen type I and heat shock protein 47 in A549 cells.
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DOI：
10.1186/1471-2466-12-24
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发表时间：
2012-06-13
影响因子：
3.1
通讯作者：
Kohno S
中科院分区：
文献类型：
--
作者：
Hisatomi K;Mukae H;Sakamoto N;Ishimatsu Y;Kakugawa T;Hara S;Fujita H;Nakamichi S;Oku H;Urata Y;Kubota H;Nagata K;Kohno S
吡非尼酮是一种新型抗纤维化和抗炎剂，可抑制动物模型和特发性肺纤维化 (IPF) 患者的纤维化进展。我们之前表明，在体外用转化生长因子 (TGF)-β1 刺激的人肺成纤维细胞中，吡非尼酮可抑制 I 型胶原蛋白和热休克蛋白 (HSP) 47（一种胶原蛋白特异性分子伴侣）的过度表达。在博莱霉素诱导的肺纤维化动物模型中，吡非尼酮也减少了 HSP47 阳性 II 型肺细胞和成纤维细胞数量的增加。本研究在体外评估了吡非尼酮对人肺泡上皮细胞系 A549 细胞中 I 型胶原蛋白和 HSP47 表达的影响。通过Northern印迹或实时PCR评估用TGF-β1刺激的A549细胞中I型胶原、HSP47和E-钙粘蛋白mRNA的表达。通过免疫细胞化学染色评估 I 型胶原蛋白、HSP47 和纤连蛋白的表达。 TGF-β1刺激A549细胞中I型胶原和HSP47 mRNA和蛋白的表达，而吡非尼酮显着抑制这一过程。 Pirfenidone 还抑制 TGF-β1 诱导的 A549 细胞中成纤维细胞表型标记物纤连蛋白的过度表达。我们的结论是，吡非尼酮的抗纤维化作用可能不仅通过直接抑制 I 型胶原表达来介导，还通过抑制肺泡上皮细胞中 HSP47 的表达来介导，从而导致肺纤维化中胶原合成减少。此外，吡非尼酮可能部分抑制上皮-间质转化。
Pirfenidone is a novel anti-fibrotic and anti-inflammatory agent that inhibits the progression of fibrosis in animal models and in patients with idiopathic pulmonary fibrosis (IPF). We previously showed that pirfenidone inhibits the over-expression of collagen type I and of heat shock protein (HSP) 47, a collagen-specific molecular chaperone, in human lung fibroblasts stimulated with transforming growth factor (TGF)-β1 in vitro. The increased numbers of HSP47-positive type II pneumocytes as well as fibroblasts were also diminished by pirfenidone in an animal model of pulmonary fibrosis induced by bleomycin. The present study evaluates the effects of pirfenidone on collagen type I and HSP47 expression in the human alveolar epithelial cell line, A549 cells in vitro. The expression of collagen type I, HSP47 and E-cadherin mRNAs in A549 cells stimulated with TGF-β1 was evaluated by Northern blotting or real-time PCR. The expression of collagen type I, HSP47 and fibronectin proteins was assessed by immunocytochemical staining. TGF-β1 stimulated collagen type I and HSP47 mRNA and protein expression in A549 cells, and pirfenidone significantly inhibited this process. Pirfenidone also inhibited over-expression of the fibroblast phenotypic marker fibronectin in A549 cells induced by TGF-β1. We concluded that the anti-fibrotic effects of pirfenidone might be mediated not only through the direct inhibition of collagen type I expression but also through the inhibition of HSP47 expression in alveolar epithelial cells, which results in reduced collagen synthesis in lung fibrosis. Furthermore, pirfenidone might partially inhibit the epithelial-mesenchymal transition.
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DOI：
10.1164/ajrccm.159.4.9805017
发表时间：
1999-04-01
影响因子：
24.7
作者：
Raghu, G;Johnson, WC;Mageto, Y
通讯作者：
Mageto, Y
DOI：
10.1513/pats.200601-004tk
发表时间：
2006-06-01
期刊：
Proceedings of the American Thoracic Society
影响因子：
--
作者：
Willis, Brigham C;duBois, Roland M;Borok, Zea
通讯作者：
Borok, Zea
DOI：
10.1152/ajplung.00305.2002
发表时间：
2003-10-01
影响因子：
4.9
作者：
Ishii, H;Mukae, H;Kohno, S
通讯作者：
Kohno, S
影响因子：
19.6
作者：
Shioshita, K;Miyazaki, M;Kohno, S
通讯作者：
Kohno, S
影响因子：
24.3
作者：
Kakugawa, T;Mukae, H;Kohno, S
通讯作者：
Kohno, S