Preventive approach against drug-induced pulmonary fibrosis through the suppression of epithelial-mesenchymal transition
Preventive approach against drug-induced pulmonary fibrosis through the suppression of epithelial-mesenchymal transition
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DOI：
10.32604/biocell.2022.019667
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发表时间：
2022-02-24
期刊：
影响因子：
1.2
通讯作者：
Takano, Mikihisa
中科院分区：
文献类型：
--
作者：
Kawami, Masashi;Yumoto, Ryoko;Takano, Mikihisa
一些药物引起肺损伤，继而导致肺纤维化等严重肺部疾病作为药物的不良反应。然而，由于对各种表现出肺毒性的药物的共同预防靶点认识不足，目前还没有建立有效的预防药物相关性肺纤维化的方法。上皮-间充质转化(EMT)是上皮细胞向间充质状态的一种表型改变，通过将受损的肺泡上皮转化为肌成纤维细胞，促进肺纤维化的发展。由于已有几种具有肺毒性的药物被报道可以诱导EMT，EMT在药物和肺纤维化之间起到了桥梁作用。越来越多的证据支持EMT作为药物诱导的肺纤维化的预防靶点的潜力。此外，由于主要药理作用与药物诱导的肺间质纤维化的机制不同，基于抑制肺间质纤维化的预防是可能的，并将有助于药物的持续临床治疗，以避免肺间质纤维化。此外，靶向EMT似乎足以起到预防作用，因为在博莱霉素诱导的大鼠肺损伤模型中，受损的肺泡上皮细胞的EMT发生在整个肺的病理生理状态之前。这一观点涉及通过抑制EMT来预防药物引起的肺纤维化的好处和前景，这一点很少被讨论。
A number of drugs induce pulmonary injury and subsequently lead to serious lung diseases such as pulmonary fibrosis as the adverse drug reactions. However, an effective preventive approach against drug-induced pulmonary fibrosis has not been established due to poor understanding of common preventive targets in a variety of drugs showing pulmonary toxicity. Epithelial-mesenchymal transition (EMT), a cellular phenotypic change of the epithelial to mesenchymal state, contributes to the development of pulmonary fibrosis through the conversion of damaged alveolar epithelium into myofibroblasts. As several drugs with pulmonary toxicity have been reported to induce EMT, EMT serves as a bridge between the drugs and pulmonary fibrosis. Accumulated evidence supports the potential of EMT as a preventive target against drug-induced pulmonary fibrosis. Additionally, since there are mechanistic differences between the main pharmacological effect and EMT induced by the drug, prevention based on EMT suppression would be possible and would contribute to continuous clinical treatment with the drug to avoid EMT-mediated serious pulmonary fibrosis. Furthermore, targeting EMT seems to be adequate for exerting a preventive effect since EMT in damaged alveolar epithelial cells occurs prior to the development of the pathophysiological state of the whole lung in a bleomycin-induced lung injury rat model. This viewpoint deals with the benefits and perspectives of preventive approaches against drug-induced pulmonary fibrosis through the suppression of EMT, which has rarely been addressed.