Department of Medical Biology, Institute of Rural Health, 20-090 Lublin, Poland.
Heidelberg Institute of Global Health (HIGH), Faculty of Medicine and University Hospital, Heidelberg University, 69117 Heidelberg, Germany.
Int J Mol Sci. 2022 Oct 27;23(21):13039. doi: 10.3390/ijms232113039.
Pulmonary fibrosis is becoming an increasingly common pathology worldwide. Unfortunately, this disorder is characterized by a bad prognosis: no treatment is known, and the survival rate is dramatically low. One of the most frequent reasons for pulmonary fibrosis is hypersensitivity pneumonitis (HP). As the main mechanism of pulmonary fibrosis is a pathology of the repair of wounded pulmonary epithelium with a pivotal role in epithelial-mesenchymal transition (EMT), we assumed that EMT silencing could prevent disease development. Because of several biological features including wound healing promotion, an ideal candidate for use in the treatment of pulmonary fibrosis seems to be cathelicidin. The aim of the studies was to understand the influence of cathelicidin on the EMT process occurring during lung fibrosis development in the course of HP. Cathelicidin's impact on EMT was examined in a murine model of HP, wherein lung fibrosis was induced by chronic exposure to extract of (SE-PA) by real-time PCR and Western blotting. Studies revealed that mouse exposure to cathelicidin did not cause any side changes in the expression of investigated genes/proteins. Simultaneously, cathelicidin administered together or after SE-PA decreased the elevated level of myofibroblast markers (/α-smooth muscle actin, /N-cadherin, /Fibronectin, /vimentin) and increased the lowered level of epithelial markers (/E-cadherin, /occludin). Cathelicidin provided with SE-PA or after cessation of SE-PA inhalations reduced the expression of EMT-associated factors (/β-catenin, /NFκB, /Snail, /TGFβ1 /ZEB1, /ZEB2) elevated by . Cathelicidin's beneficial impact on the expression of genes/proteins involved in EMT was observed during and after the HP development; however, cathelicidin was not able to completely neutralize the negative changes. Nevertheless, significant EMT silencing in response to cathelicidin suggested the possibility of its use in the prevention/treatment of pulmonary fibrosis.
肺纤维化在全球范围内变得越来越常见。不幸的是，这种疾病的预后很差：目前尚无已知的治疗方法，存活率极低。肺纤维化最常见的原因之一是过敏性肺炎（HP）。由于肺纤维化的主要机制是受伤的肺上皮细胞修复的病理学，在上皮-间充质转化（EMT）中起着关键作用，我们假设 EMT 沉默可以预防疾病的发展。由于包括促进伤口愈合在内的多种生物学特性，一种理想的候选药物似乎是抗菌肽。本研究的目的是了解抗菌肽对 HP 过程中肺纤维化发展过程中 EMT 过程的影响。通过实时 PCR 和 Western blot 检查抗菌肽对 HP 小鼠模型中 EMT 的影响，其中通过慢性暴露于 （SE-PA） 诱导肺纤维化。研究表明，抗菌肽暴露不会引起研究基因/蛋白表达的任何变化。同时，与 SE-PA 一起或在 SE-PA 吸入后给予抗菌肽会降低成肌纤维标志物（/α-平滑肌肌动蛋白、/N-钙黏蛋白、/纤连蛋白、/波形蛋白）的升高水平，并增加上皮标志物（/E-钙黏蛋白、/occludin）的降低水平。与 SE-PA 一起给予抗菌肽或在 SE-PA 吸入停止后会降低由 上调的 EMT 相关因子（/β-catenin、/NFκB、/Snail、/TGFβ1 /ZEB1、/ZEB2）的表达。在 HP 发展期间和之后，观察到抗菌肽对 EMT 相关基因/蛋白表达的有益影响；然而，抗菌肽无法完全中和负面变化。尽管如此，抗菌肽对 EMT 的显著沉默表明其在预防/治疗肺纤维化中的可能性。
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