Secreted Phosphoprotein 1 and Sex-Specific Differences in Silica-Induced Pulmonary Fibrosis in Mice.
Secreted Phosphoprotein 1 and Sex-Specific Differences in Silica-Induced Pulmonary Fibrosis in Mice.
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DOI：
10.1289/ehp.1510335
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发表时间：
2016-08
影响因子：
10.4
通讯作者：
Fattman CL
中科院分区：
文献类型：
--
作者：
Latoche JD;Ufelle AC;Fazzi F;Ganguly K;Leikauf GD;Fattman CL
纤维化肺病主要发生在男性中，报告描述了受影响女性的生存率更高。雄性小鼠对二氧化硅诱导的肺纤维化比二氧化硅处理的雌性小鼠更敏感。分泌型磷蛋白1（SPP 1，也称为骨桥蛋白）在肺纤维化中增加，Spp 1转录可能受雌激素或雌激素受体相关受体调节。我们确定二氧化硅诱导的SPP 1水平的差异是否有助于肺纤维化的性别差异。雄性和雌性小鼠用0.2 g/kg气管内二氧化硅处理，并在暴露后1、3或14天评估肺损伤。用二氧化硅处理基因靶向（Spp 1-/-）小鼠、对照Spp 1 +/+（C57 BL/6 J）小鼠、卵巢切除（OVX）雌性小鼠和雌激素处理雄性小鼠，并评估肺损伤。雄性小鼠肺组织、支气管肺泡灌洗液和血清中二氧化硅诱导的SPP 1增加多于雌性小鼠。二氧化硅处理后，与雌性Spp 1 +/+小鼠相比，雌性Spp 1-/-小鼠的支气管肺泡灌洗液细胞浸润减少，与雄性Spp 1 +/+小鼠相比，雄性Spp 1-/-小鼠的肺羟脯氨酸减少。与二氧化硅处理的假手术雌性小鼠相比，OVX雌性小鼠对二氧化硅的肺SPP 1表达增加。二氧化硅诱导的肺胶原蛋白和羟脯氨酸（纤维化的标志物），和SPP 1水平下降，雌激素治疗的男性相比，未经处理的男性。这些发现表明，SPP 1水平的性别特异性差异有助于雄性和雌性小鼠对二氧化硅诱导的纤维化发展的不同敏感性。[10]李文辉，李文辉. 2016.二氧化硅诱导的小鼠肺纤维化中的分泌性磷蛋白1和性别特异性差异。环境健康展望124：1199-1207; http：dx.doi.org/10.1289/ehp.1510335
Fibrotic lung diseases occur predominantly in males, and reports describe better survival in affected females. Male mice are more sensitive to silica-induced lung fibrosis than silica-treated female mice. Secreted phosphoprotein 1 (SPP1, also known as osteopontin) increases in pulmonary fibrosis, and Spp1 transcription may be regulated by estrogen or estrogen receptor–related receptors. We determined whether differences in silica-induced SPP1 levels contribute to sex differences in lung fibrosis. Male and female mice were treated with 0.2 g/kg intratracheal silica, and lung injury was assessed 1, 3, or 14 days post-exposure. Gene-targeted (Spp1–/–) mice, control Spp1+/+ (C57BL/6J) mice, ovariectomized (OVX) female mice, and estrogen-treated male mice were treated with silica, and lung injury was assessed. Silica-induced SPP1 in lung tissue, bronchoalveolar lavage, and serum increased more in male than in female mice. Following silica treatment, bronchoalveolar lavage cell infiltrates decreased in female Spp1–/– mice compared with female Spp1+/+ mice, and lung hydroxyproline decreased in male Spp1–/– mice compared with male Spp1+/+ mice. OVX female mice had increased lung SPP1 expression in response to silica compared with silica-treated sham female mice. Silica-induced lung collagen and hydroxyproline (markers of fibrosis), and SPP1 levels decreased in estrogen-treated males compared with untreated males. These findings suggest that sex-specific differences in SPP1 levels contribute to the differential sensitivity of male and female mice to the development of silica-induced fibrosis. Latoche JD, Ufelle AC, Fazzi F, Ganguly K, Leikauf GD, Fattman CL. 2016. Secreted phosphoprotein 1 and sex-specific differences in silica-induced pulmonary fibrosis in mice. Environ Health Perspect 124:1199–1207; http://dx.doi.org/10.1289/ehp.1510335