Bone marrow-derived fibrocytes contribute to liver fibrosis.
Bone marrow-derived fibrocytes contribute to liver fibrosis.
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DOI：
10.1177/1535370215584933
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发表时间：
2015-06
期刊：
影响因子：
--
通讯作者：
Kisseleva T
中科院分区：
文献类型：
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作者：
Xu J;Kisseleva T
慢性肝损伤通常会导致肝纤维化，这是一种与循环TGF-β1和脂多糖（LPS）水平升高、肌成纤维细胞活化和细胞外基质（主要是I型胶原）广泛沉积相关的疾病。肝星状细胞（HSC）被认为是损伤肝脏中肌成纤维细胞的主要但不是唯一来源。肝肌成纤维细胞也可能来源于门静脉成纤维细胞、间充质细胞和纤维细胞。自1994年Bucala博士及其同事发现纤维细胞以来，这些骨髓（BM）衍生的I型胶原蛋白产生的CD 45+细胞仍然是造血系统中最迷人的细胞。由于能够分化成I型胶原蛋白产生细胞/肌成纤维细胞，纤维细胞与肝、皮肤、肺和肾纤维化的发病机制有关。然而，不同器官的研究往往包含有争议的结果，招募到损伤部位的纤维细胞的数量，以及它们的生物学功能。此外，纤维细胞参与脓毒症的发病机制，并显示具有抗微生物活性。最后，在响应特定的刺激，纤维细胞可以产生完全分化的巨噬细胞，这表明在与造血细胞的高可塑性的同时，纤维细胞表现出祖细胞特性。在这里，我们总结了我们目前对CD 45 + I型胶原+BM衍生细胞在纤维化肝损伤和败血症中的作用的理解，并讨论了支持纤维细胞在促纤维化和/或促炎症反应中的关键作用的最新证据。
Chronic liver injury often leads to hepatic fibrosis, a condition associated with increased levels of circulating TGF-β1 and lipopolysaccharide (LPS), activation of myofibroblasts, and extensive deposition of extracellular matrix, mostly collagen type I. Hepatic stellate cells (HSCs) are considered to be the major but not the only source of myofibroblasts in the injured liver. Hepatic myofibroblasts may also originate from portal fibroblasts, mesenchymal cells and fibrocytes. Since the discovery of fibrocytes in 1994 by Dr. Bucala and colleagues, these bone marrow (BM)-derived collagen Type I-producing CD45+ cells remain the most fascinating cells of the hematopoietic system. Due to the ability to differentiate into collagen Type I producing cells/myofibroblasts, fibrocytes were implicated in the pathogenesis of liver, skin, lung, and kidney fibrosis. However, studies of different organs often contain controversial results on the number of fibrocytes recruited to the site of injury, and their biological function. Furthermore, fibrocytes were implicated in pathogenesis of sepsis, and were shown to possess anti-microbial activity. Finally, in response to specific stimuli, fibrocytes can give rise to fully differentiated macrophages, suggesting that in concurrence with high plasticity of hematopoietic cells, fibrocytes exhibit progenitor properties. Here we summarize our current understanding of the role of CD45+Collagen Type I+ BM-derived cells in response to fibrogenic liver injury and septicemia and discuss the most recent evidence supporting the critical role of fibrocytes in the mediation of pro-fibrogenic and/or pro-inflammatory responses.