Abstract：
Idiopathic pulmonary fibrosis is a progressive lung disease characterized by excessive extracellular matrix accumulation and myofibroblast proliferation with limited treatment options available. M2 macrophages are pivotal in pulmonary fibrosis, where they induce the epithelial-to-mesenchymal and fibroblast-to-myofibroblast transitions. In this study, we evaluated whether MEL-dKLA, a hybrid peptide that can eliminate M2 macrophages, could attenuate pulmonary fibrosis in a cell co-culture system and in a bleomycin-induced mouse model. Our findings demonstrated that the removal of M2 macrophages using MEL-dKLA stimulated reprogramming to an antifibrotic environment, which effectively suppressed epithelial-to-mesenchymal and fibroblast-to-myofibroblast transition responses in lung epithelial and fibroblast cells and reduced extracellular matrix accumulation both in vivo and in vitro. Moreover, MEL-dKLA exhibited antifibrotic efficacy without damaging tissue-resident macrophages in the bleomycin-induced mouse model. Collectively, our findings suggest that MEL-dKLA may be a new therapeutic option for the treatment of idiopathic pulmonary fibrosis.
摘要：
特发性肺纤维化是一种进行性肺病，其特征是细胞外基质过度积累和肌成纤维细胞增殖，治疗选择有限。M2巨噬细胞在肺纤维化中至关重要，它们诱导上皮到间质和成纤维细胞到肌成纤维细胞的转变。在这项研究中,我们评估了MEL-dKLA，一种可以消除M2巨噬细胞的杂合肽，可以在细胞共培养系统和博来霉素诱导的小鼠模型中减轻肺纤维化。我们的发现表明，使用MEL-dKLA去除M2巨噬细胞刺激重编程到抗纤维化环境，有效抑制肺上皮和成纤维细胞的上皮-间质和成纤维细胞-肌成纤维细胞的转化反应，并减少体内和体外细胞外基质的积累。此外，MEL-dKLA在博来霉素诱导的小鼠模型中表现出抗纤维化功效而不损伤组织驻留的巨噬细胞。总的来说，我们的研究结果表明,MEL-dKLA可能是治疗特发性肺纤维化的一种新的治疗选择.
