Macrophages promote renal fibrosis through direct and indirect mechanisms.
Macrophages promote renal fibrosis through direct and indirect mechanisms.
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DOI：
10.1038/kisup.2014.7
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发表时间：
2014-11
影响因子：
5.5
通讯作者：
Lan HY
中科院分区：
文献类型：
--
作者：
Nikolic-Paterson DJ;Wang S;Lan HY
巨噬细胞积聚与人类和实验性肾脏疾病中的活动性肾纤维化之间存在密切的时空关系。已经鉴定了不同亚型的巨噬细胞。促炎性M1型巨噬细胞可引起急性组织损伤，而促纤维化M2型巨噬细胞可在持续的组织损伤期间驱动纤维化反应。巨噬细胞通过成纤维细胞的募集、增殖和活化诱导纤维化。此外，有越来越多的证据支持巨噬细胞通过在称为巨噬细胞-肌成纤维细胞转化（MMT）的过程中转化为肌成纤维细胞而直接发挥纤维化作用。巨噬细胞和肌成纤维细胞抗原的共表达鉴定了人类和实验性纤维化肾病中的MMT过程。这种共表达鉴定了肾纤维化期间存在的大部分肌成纤维细胞群体的骨髓来源的单核细胞/巨噬细胞来源。这种假设的MMT途径代表了一种新的机制，将富含巨噬细胞的急性炎症与肌成纤维细胞积聚和肾纤维化的进展联系起来。需要进一步的研究来确定调节MMT过程的分子机制，巨噬细胞群体可以经历MMT，并确定MMT在肾纤维化过程中对活性胶原沉积的功能贡献。
There is a close spatial and temporal relationship between macrophage accumulation and active renal fibrosis in human and experimental kidney disease. Different subtypes of macrophages have been identified. Pro-inflammatory M1-type macrophages can cause acute tissue injury, whereas pro-fibrotic M2-type macrophages can drive the fibrotic response during ongoing tissue injury. Macrophages induce fibrosis through the recruitment, proliferation, and activation of fibroblasts. In addition, there is accumulating evidence that supports a direct fibrotic role for macrophages via transition into myofibroblasts in a process termed macrophage–myofibroblast transition (MMT). Co-expression of macrophage and myofibroblast antigens identifies the MMT process both in human and experimental fibrotic kidney disease. This co-expression identifies a bone marrow–derived monocyte/macrophage source for a substantial proportion of the myofibroblast population present during renal fibrosis. This postulated MMT pathway represents a new mechanism linking macrophage-rich acute inflammation with the progression to myofibroblast accumulation and renal fibrosis. Further studies are required to identify the molecular mechanisms regulating the MMT process, which macrophage populations can undergo MMT, and to define the functional contribution of MMT to active collagen deposition during renal fibrosis.