Extracellular matrix of early pulmonary fibrosis modifies the polarization of
Extracellular matrix of early pulmonary fibrosis modifies the polarization of
复制标题
DOI：
10.1016/j.intimp.2022.109179
复制
发表时间：
2022
影响因子：
5.6
通讯作者：
陈纯
中科院分区：
文献类型：
--
作者：
张彦伟;朱丽花;洪金省;陈纯
Macrophage polarization is modulated by many different stimuli. However, the effect of fibrotic extracellular matrix (ECM) on macrophage polarization remains unclear. In this study, a mouse model of radiation induced pulmonary fibrosis (RIPF) was established. Alveolar macrophages (AMs) were seeded on separated decellularized ECM respectively derived from early RIPF lung tissue (dECM-RIPF) and normal lung tissue (dECM-Nor), on which the polarization of AMs was examined. By way of bio-AFM analysis, a significant difference in surface roughness, but no difference in stiffness, was found between dECM-RIPF and dECM-Nor. Compared with dECMNor, dECM-RIPF induced a higher M1 activation and increased the levels of TNF-α, IL-6 and IL-1β, while it showed no significant effect M2 density. Nevertheless, such effects induced by dECM-RIPF could be abrogated by the integrin pan-inhibitor. Furthermore, dECM-RIPF caused integrin-dependent activation of NFκB, and NFκB inhibitor was capable of inhibiting dECM-RIPF-induced AMs proliferation and M1 activation. Animal experiments showed that NFκB inhibitor alleviated RIPF mainly through inhibiting M1 activation and down-regulating the levels of inflammatory cytokines. Our results showed that differential biophysical signaling from the fibrotic ECM of early RIPF promoted AMs polarization towards a M1 phenotype via integrin-NFκB. Inhibition of M1 activation may be an attractive approach for treating RIPF.
