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诃子酸对城市颗粒物作用下肺泡上皮细胞向间充质细胞转分化的抑制作用:共处理和后处理暴露方式的影响

Inhibitory Effect of Chebulic Acid on Alveolar Epithelial to Mesenchymal Transition in Response to Urban Particulate Matter Using Co-treatment and Post-treatment Exposure.

机构信息

Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University.

出版信息

Biol Pharm Bull. 2019;42(8):1322-1331. doi: 10.1248/bpb.b19-00061.

Abstract

Urban particulate matter (UPM) is atmospheric particulate samples obtained from industrialized urban areas. It is known that pulmonary fibrosis can result directly or indirectly from particulate matter. In this study, the protective effect of chebulic acid (CA) against UPM-induced epithelial-mesenchymal transition (EMT) in the pulmonary alveolar epithelial (PAE) cells were investigated. Our findings revealed that PAE cells were changed from the epithelial phenotype to mesenchymal one after exposure to UPM. Furthermore, co-treatment and post-treatment of CA inhibited EMT progression. Especially the key epithelial marker, E-cadherin, was down-regulated by UPM and recovered by CA. Also, gelatin zymogram showed that the activity of matrix metalloproteinase (MMP)-2 and MMP-9 was decreased by co-treatment and post-treatment of CA. Further investigation revealed that CA attenuated UPM-stimulated PAE cells invasion ability. These data showed that UPM promoted PAE cells invasion, reactive oxygen species-mediated extracellular matrix degradation and CA reduced the potential health risks associated with UPM.

摘要

城市颗粒物(UPM)是从工业化城市地区获得的大气颗粒物样本。已知颗粒物可直接或间接导致肺纤维化。在这项研究中,研究了诃子酸(CA)对 UPM 诱导的肺泡上皮(PAE)细胞上皮-间充质转化(EMT)的保护作用。我们的研究结果表明,PAE 细胞在暴露于 UPM 后从上皮表型转变为间充质表型。此外,CA 的共同处理和后处理抑制了 EMT 的进展。特别是关键的上皮标志物 E-钙黏蛋白被 UPM 下调,并被 CA 恢复。此外,明胶酶谱显示,基质金属蛋白酶(MMP)-2 和 MMP-9 的活性通过 CA 的共同处理和后处理而降低。进一步的研究表明,CA 减弱了 UPM 刺激的 PAE 细胞侵袭能力。这些数据表明,UPM 促进了 PAE 细胞的侵袭,活性氧介导的细胞外基质降解,而 CA 降低了与 UPM 相关的潜在健康风险。

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