肺部 dECM 基质水凝胶通过抑制 M2 巨噬细胞极化逆转博莱霉素诱导的肺纤维化

IF 8.2 2区 医学 Q1 ENGINEERING, BIOMEDICAL
Xinglong Zhu, Ying Yang, Shengqiang Mao, Qin Liu, Yanan Li, Yongfeng Yang, Mengyu Gao, Ji Bao, Weimin Li, Yi Li
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摘要

本文章由计算机程序翻译,如有差异,请以英文原文为准。
Lung dECM matrikine-based hydrogel reverses bleomycin-induced pulmonary fibrosis by suppressing M2 macrophage polarization.

Background: Recent studies have shown promising results using decellularized extracellular matrix (dECM) matrikines-based hydrogel as attractive strategies for preventing and alleviating fibrosis. Methods & Results: Porcine lung decellularization and pepsin digestion were used to prepare the lung dECM hydrogel. Proteomic analysis revealed that the lung dECM hydrogel was enriched in glycoproteins, collagens, laminins, fibrinogen, held receptors, and bound growth factors. With porous structures and good mechanical properties and stability, the lung dECM hydrogel showed low cytotoxicity and good biocompatibility both in vitro and in vivo. The lung dECM hydrogel was further administered to verify the safety and effectiveness of reversing pulmonary fibrosis in a bleomycin induced rat model. The results revealed a relatively complete alveolar structure with less inflammatory infiltration and a reduced amount of collagen fiber deposition. TMT quantification proteomic analyses revealed significant downregulation of proteins, pathways, and interactions involved in the regulation of ECM components, tissue remodeling, inflammation, and the cytoskeleton and indicated that fibrosis-related proteins were obviously downregulated and inflammation-related proteins were significantly changed, particularly in macrophages, after administration of the lung dECM hydrogel. Multiplex immunohistochemical (mIHC) staining of lung tissue revealed that the inflammatory response was regulated by the lung dECM hydrogel, as indicated by a decrease in the number of CD3+ T cells and macrophages and the suppression of M2 macrophage polarization. Gene set enrichment analysis revealed that downregulated ficolin signaling was enriched in macrophages after lung dECM hydrogel administration, and the findings were verified in lung tissue by mIHC. Additionally, the effects of ficolin B proteins on macrophage polarization were proved in vitro. Conclusion: This study suggested that the lung dECM hydrogel can reverse pulmonary fibrosis by suppressing M2 macrophage polarization through downregulation of the ficolin signaling pathway. Thus, the dECM hydrogel represent a promising class of biological materials for use in regenerative medicine.

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来源期刊
Biofabrication
Biofabrication ENGINEERING, BIOMEDICAL-MATERIALS SCIENCE, BIOMATERIALS
CiteScore
17.40
自引率
3.30%
发文量
118
审稿时长
2 months
期刊介绍: Biofabrication is dedicated to advancing cutting-edge research on the utilization of cells, proteins, biological materials, and biomaterials as fundamental components for the construction of biological systems and/or therapeutic products. Additionally, it proudly serves as the official journal of the International Society for Biofabrication (ISBF).
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