Liu Qicai, Zhang Shuyu, Liu Guozhong, Zhou Huiling, Guo Yujia, Gao Feng, Weng Shangeng
Center of Reproductive Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350028, Fujian, China.
Department of Laboratory Medicine, Fujian Maternity and Child Health Hospital, Fuzhou 350004, Fujian, China; Department of Laboratory Medicine, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou 350005, Fujian, China.
Int Immunopharmacol. 2023 Nov;124(Pt A):110891. doi: 10.1016/j.intimp.2023.110891. Epub 2023 Sep 7.
The aim of this study was to describe the effects of adropin deficiency on the distribution, phenotype and pathological phenotype of macrophages in colonic and mesenteric tissues of AdrKO (Enho) mice, so as to explore the mechanism of adropin deficiency in spontaneous and experimental colitis. In this study, RNA-seq and metabonomics were used to screen the regulatory mechanism of adropin on the phenotypic transformation of macrophages. We found that adropin levels in active UC patients were significantly lower than those in normal subjects and remission UC patients, and at the same time, a large number of proinflammatory M1-type macrophages were infiltrated in the mesenteric tissue of colonic tissues from UC and CD patients. At the same time, spontaneous colitis occurred in Enho-/- (adropin-deficient)C57BL/6 mice, and there was an imbalance of M2 → M1 polarization of macrophages in colon and mesentery of Enho-/- mice. In vivo, it has showed that adropin deficiency could exacerbate the pathological phenotype of colitis induced by TNBS. In vitro, adropin was used to intervene RAW264.7 macrophages, and then combined analysis of RNA-seq and metabolomics demonstrated that adropin regulated lipid metabolism of macrophages through PPARγ, thus promoting the repolarization of macrophages from M1 to M2. Adropin deficiency led to an imbalance in the phenotypic distribution of macrophages infiltrating the colon and mesenteric tissues, namely, an increase in M1 type, which led to the occurrence and development of colitis.
本研究旨在描述内源性降钙素原缺乏对AdrKO（Enho）小鼠结肠和肠系膜组织中巨噬细胞分布、表型及病理表型的影响，以探讨内源性降钙素原缺乏在自发性和实验性结肠炎中的作用机制。在本研究中，采用RNA测序和代谢组学技术筛选内源性降钙素原对巨噬细胞表型转化的调控机制。我们发现，活动期溃疡性结肠炎患者的内源性降钙素原水平显著低于正常受试者和缓解期溃疡性结肠炎患者，同时，溃疡性结肠炎和克罗恩病患者结肠组织的肠系膜组织中有大量促炎性M1型巨噬细胞浸润。同时，Enho-/-（内源性降钙素原缺乏）C57BL/6小鼠发生自发性结肠炎，Enho-/-小鼠结肠和肠系膜中巨噬细胞的M2→M1极化失衡。在体内，结果表明内源性降钙素原缺乏可加重三硝基苯磺酸诱导的结肠炎的病理表型。在体外，用内源性降钙素原干预RAW264.7巨噬细胞，然后结合RNA测序和代谢组学分析表明，内源性降钙素原通过过氧化物酶体增殖物激活受体γ调节巨噬细胞的脂质代谢，从而促进巨噬细胞从M1型向M2型复极化。内源性降钙素原缺乏导致浸润结肠和肠系膜组织的巨噬细胞表型分布失衡，即M1型增加，从而导致结肠炎的发生和发展。
