Molecular mechanism of tissue fibrosis and develpment of revolutionary anti-fibrotic therapy

纤维化是多种慢性炎症性疾病最终的、常见的病理结果。在本研究中，我们重点关注巨噬细胞诱导的c型凝集素（Mincle），一种识别结核分枝杆菌并在肥胖脂肪组织中诱导的病原体传感器，并研究了Mincle在脂肪组织纤维化中的调节作用。在肥胖脂肪组织中，Mincle主要在促炎M1巨噬细胞中表达。肌环刺激可引起腹膜巨噬细胞中与纤维形成相关的基因上调。此外，海藻糖6,6'-二mycolate（一种外源性Mincle配体）刺激脂肪组织中的Mincle可导致脂肪组织纤维化。这些观察结果表明，肥胖脂肪组织中Mincle的激活导致脂肪组织纤维化的进展，从而表明Mincle拮抗剂为慢性纤维化疾病提供了一种新的抗纤维化治疗方法。

Fibrosis is a final, common pathological outcome of a variety of chronic inflammatory diseases. In this study, we focused on Macrophage-inducible C-type lectin (Mincle), a pathogen sensor that recognizes Mycobacterium tuberculosis and is induced in obese adipose tissue and investigated the role of Mincle in the regulation of adipose tissue fibrosis. In the obese adipose tissue, Mincle was expressed mainly in proinflammatory M1 macrophages. Mincle stimulation caused the upregulation of genes related to fibrogenesis in peritoneal macrophages. Furthermore, Mincle stimulation by trehalose 6,6'-dimycolate, an exogenous ligand for Mincle, in adipose tissue resulted in adipose tissue fibrosis. These observations suggest that Mincle activation in obese adipose tissue leads to the progression of adipose tissue fibrosis, thereby suggesting that Mincle antagonism offers an novel anti-fibrotic therapy for chronic fibrotic diseases.