The types of hepatic myofibroblasts contributing to liver fibrosis of different etiologies.
The types of hepatic myofibroblasts contributing to liver fibrosis of different etiologies.
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DOI：
10.3389/fphar.2014.00167
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发表时间：
2014
影响因子：
5.6
通讯作者：
Kisseleva T
中科院分区：
文献类型：
--
作者：
Xu J;Liu X;Koyama Y;Wang P;Lan T;Kim IG;Kim IH;Ma HY;Kisseleva T
肝纤维化由正常伤口愈合、炎症、肌成纤维细胞活化和细胞外基质（ECM）沉积的失调引起。慢性肝损伤导致肝细胞死亡和凋亡小体形成，凋亡小体反过来释放因子，将炎性细胞（中性粒细胞、单核细胞、巨噬细胞和淋巴细胞）募集到受损的肝脏。肝巨噬细胞（枯否细胞）产生TGFβ1和其他炎性细胞因子，这些细胞因子激活I型胶原蛋白，产生肌成纤维细胞，这些细胞在正常肝脏中不存在。TGFβ1的分泌和肌成纤维细胞的激活在不同病因的肝纤维化的发病机制中发挥着关键作用。虽然纤维化肌成纤维细胞的组成根据肝损伤的病因而变化，但在肝纤维化的实验模型和肝病患者中，肝驻留肝星状细胞和门静脉成纤维细胞是纤维化肝中肌成纤维细胞的主要来源。多项研究表明，肝损伤停止后，肝纤维化可以逆转。肝纤维化的消退伴随着纤维化肌成纤维细胞的消失，随后是纤维性瘢痕的再吸收。肌成纤维细胞要么停止生长，要么进入静止样状态（例如，停止胶原蛋白产生和部分恢复脂肪生成基因表达）。肝纤维化的消退与巨噬细胞的募集有关，巨噬细胞分泌基质降解酶（基质金属蛋白酶、胶原酶）并负责纤维化消退。然而，长期/重复的肝损伤可能导致ECM的不可逆交联和不可切割的胶原纤维的形成。晚期纤维化进展为肝硬化和肝细胞癌。本文综述了不同细胞类型对肝纤维化中肌成纤维细胞的作用和贡献。
Liver fibrosis results from dysregulation of normal wound healing, inflammation, activation of myofibroblasts, and deposition of extracellular matrix (ECM). Chronic liver injury causes death of hepatocytes and formation of apoptotic bodies, which in turn, release factors that recruit inflammatory cells (neutrophils, monocytes, macrophages, and lymphocytes) to the injured liver. Hepatic macrophages (Kupffer cells) produce TGFβ1 and other inflammatory cytokines that activate Collagen Type I producing myofibroblasts, which are not present in the normal liver. Secretion of TGFβ1 and activation of myofibroblasts play a critical role in the pathogenesis of liver fibrosis of different etiologies. Although the composition of fibrogenic myofibroblasts varies dependent on etiology of liver injury, liver resident hepatic stellate cells and portal fibroblasts are the major source of myofibroblasts in fibrotic liver in both experimental models of liver fibrosis and in patients with liver disease. Several studies have demonstrated that hepatic fibrosis can reverse upon cessation of liver injury. Regression of liver fibrosis is accompanied by the disappearance of fibrogenic myofibroblasts followed by resorption of the fibrous scar. Myofibroblasts either apoptose or inactivate into a quiescent-like state (e.g., stop collagen production and partially restore expression of lipogenic genes). Resolution of liver fibrosis is associated with recruitment of macrophages that secrete matrix-degrading enzymes (matrix metalloproteinase, collagenases) and are responsible for fibrosis resolution. However, prolonged/repeated liver injury may cause irreversible crosslinking of ECM and formation of uncleavable collagen fibers. Advanced fibrosis progresses to cirrhosis and hepatocellular carcinoma. The current review will summarize the role and contribution of different cell types to populations of fibrogenic myofibroblasts in fibrotic liver.
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影响因子：
25.7
作者：
Cassiman, D;Barlow, A;Pachnis, V
通讯作者：
Pachnis, V
姜黄素通过抑制胆管细胞炎症反应和门户肌纤维细胞增殖来改善MDR2 - / - 小鼠中的硬化性胆管炎。
影响因子：
24.5
作者：
Baghdasaryan A;Claudel T;Kosters A;Gumhold J;Silbert D;Thüringer A;Leski K;Fickert P;Karpen SJ;Trauner M
通讯作者：
Trauner M
DOI：
10.1073/pnas.94.12.6307
发表时间：
1997-06-10
影响因子：
11.1
作者：
Chesney, J;Bacher, M;Bucala, R
通讯作者：
Bucala, R
影响因子：
6
作者：
Asahina, K;Sato, H;Yoshizato, K
通讯作者：
Yoshizato, K
DOI：
10.1016/j.jacr.2007.08.016
发表时间：
2008-01-01
期刊：
Journal of the American College of Radiology : JACR
影响因子：
--
作者：
Bucala, Richard
通讯作者：
Bucala, Richard