维甲酸对转化生长因子β1诱导的HFL-I细胞Ⅲ型胶原、STAT3和PIAS3表达的影响  

Effect of all-trans-retinoic acid on expression of collagen Ⅲ,STAT3 and PIAS3 in TGF-β_1-stimulated human lung fibroblasts

作　　者：夏武[1] 杨宇平[1] 陈永凤[2] 程娜[1] 刘巨源[1] 

机构地区：[1]新乡医学院药学院药理学教研室,河南新乡453003 [2]新乡医学院第三附属医院呼吸内科,河南新乡453003

出　　处：《中国病理生理杂志》2012年第6期1114-1119,共6页Chinese Journal of Pathophysiology

基　　金：河南省教育厅自然科学资助项目(No.2009A310007);新乡医学院研究生科研创新支持计划资助项目(No.YJSCX201010Y)

摘　　要：目的:研究全反式维甲酸(ATRA)对转化生长因子β1(TGF-β1)诱导的人胚肺成纤维细胞(HFL-I)中Ⅲ型胶原(collagenⅢ)、信号转导子和转录激活子3(STAT3)和活化STAT3蛋白抑制剂(PIAS3)表达的影响。方法:体外培养HFL-I细胞,5μg/L TGF-β1诱导0 h、6 h、12 h、24 h、48 h和72 h后,RT-PCR法检测colla-genⅢ、STAT3和PIAS3 mRNA表达,诱导0 d、1 d、3 d和5 d后,Western blotting法检测STAT3和p-STAT3蛋白表达。不同浓度维甲酸干预,24 h后用RT-PCR法检测collagenⅢ、STAT3和PIAS3 mRNA表达,3 d后用Westernblotting法检测STAT3和p-STAT3蛋白表达。结果:TGF-β1诱导后,HFL-I细胞中collagenⅢ和STAT3 mRNA表达明显上调,PIAS3 mRNA表达明显下调,STAT3和p-STAT3蛋白表达明显上调(P<0.05)。各浓度ATRA都下调TGF-β1诱导的HFL-I细胞中collagenⅢ、STAT3 mRNA和STAT3、p-STAT3蛋白的表达,上调PIAS3 mR-NA表达(P<0.05)。结论:ATRA可通过抑制TGF-β1诱导的HFL-I细胞collagenⅢ和STAT3表达、上调PIAS3表达而起到抗肺纤维化作用。AIM： To investigate the effects of all-trans-retinoic acid （ATRA） on the expression of collagen Ⅲ, signal transducer and activator of transcription 3（STAT3） and protein inhibitor of activated STAT3 （PIAS3） in TGF-β1-stimulated human lung fibroblasts （HFL-I）. METHODS： Addition of TGF-β1 at dose of 5 μg/L were conducted to stimulate the cultured HFL-I cells. The mRNA expression of collagen Ⅲ, STAT3 and PIAS3 in the cells was determined by RT-PCR at the time of induction with TGF-β1 for 0 h, 6 h, 12 h, 24 h, 48 h and 72 h. Western blotting was also used to detect the protein levels of STAT3 and p-STAT3 at the time of induction with TGF-β1 for 1 d, 3 d and 5 d. After stimulated with TGF-β1, HFL-I cells were treated with ATRA at concentrations of 10 μmol/L, 1 μmol/L and 0.1 μmol/L. The mRNA expression of collagen Ⅲ, STAT3 and PIAS3 was detected by RT-PCR 24 h after ATRA treatment, and the protein levels of STAT3 and p-STAT3 were also assayed by Western blotting 3 d after ATRA treatment. RESULTS： The results of RT-PCR and Western blotting showed that TGF-β1 promoted the mRNA expression of collagen Ⅲ and STAT3, increased the protein levels of STAT3 and p-STAT3, and reduced the mRNA expression of PIAS3 in HFL-I cells （P〈0.05）. ATRA at different concentrations decreased the mRNA expression of collagen Ⅲ and STAT3, and protein levels of STAT3 and p-STAT3 in TGF-β1-stimulated HFL-I cells （P〈0.05）. Meanwhile, the mRNA expression of PIAS3 was obviously increased （P〈0.05）. CONCLUSION： ATRA prevents the progress of pulmonary fibrosis by down-regulating the expression of collagen Ⅲ and STAT3, and up-regulating the PIAS3 expression.

关 键 词：转化生长因子Β 全反式维甲酸 胶原Ⅲ型 信号转导子和转录激活子3 活化STAT3蛋白抑制剂 

分 类 号：R563.9[医药卫生—呼吸系统]