肝血窦内皮细胞在肝再生和肝纤维化发生中的作用

于子越; 蔺鑫; 韩英; 崔丽娜

doi:10.3969/j.issn.1001-5256.2019.09.041

肝血窦内皮细胞在肝再生和肝纤维化发生中的作用

DOI: 10.3969/j.issn.1001-5256.2019.09.041

1. 空军军医大学基础医学院学员五大队十九队
2. 空军军医大学第一附属医院消化内科

基金项目:

西京医院助推项目(XJZT18ML09)；

详细信息

中图分类号: R575.2
计量
- 文章访问数: 2128
- HTML全文浏览量: 85
- PDF下载量: 335
- 被引次数: 0
出版历程
- 收稿日期: 2019-05-15
- 出版日期: 2019-09-20

Role of liver sinusoidal endothelial cells in liver regeneration and the development of liver fibrosis

Nineteenth Team, Fifth Student Brigade of Basic Medical College, Air Force Medical University

Research funding:

摘要

摘要: 肝血窦内皮细胞是肝脏非实质细胞的主要组成细胞,是覆盖于肝窦的薄层扁平状细胞,表面富含窗孔,是肝窦和窦状间隙之间溶质交换的开放通道。肝血窦内皮细胞的分泌功能尤其是Wnt信号通路在维持Axin2+源性肝细胞的自我更新、促进肝部分切除或肝损伤时肝再生中均发挥重要的保护作用。肝损伤时,肝血窦内皮细胞结构发生改变,表现为窗孔消失和内皮下基底膜的形成,即肝窦毛细血管化。肝窦毛细血管化既是肝纤维化发生的前奏,也会促进肝纤维化的进展。肝窦内皮细胞在不同生理或病理状态下可通过信号通路的转换实现肝再生和肝纤维化调控作用的转换。肝血窦内皮细胞参与肝再生和肝纤维化机制的深入认识有望为慢性肝病的防治提供新的治疗靶点。
- 内皮细胞 /
- 肝硬化 /
- 肝再生
Abstract: As a main population of liver nonparenchymal cells, liver sinusoidal endothelial cells ( LSECs) are thin-layer flattened cells lining the hepatic sinusoid, and the fenestrae on the surface are channels for the exchange of plasma and nutrients between the hepatic sinusoid and hepatocytes. The secretion function of LSECs, especially the Wnt signaling pathway, plays an important protective effect on self-renewal of Axin2+-derived hepatocytes and liver regeneration after partial hepatectomy or liver injury. The structure of LSECs changes during liver injury, including the disappearance of fenestra and the formation of basement membrane, which is also known as hepatic sinusoidal capillarization. Hepatic sinusoidal capillarization is the starting point for liver fibrosis and also promotes the progression of liver fibrosis. The switch of the regulatory effect of LSECs in liver regeneration and liver fibrosis can be realized via signaling pathways under different physiological or pathological conditions. A deep understanding of the mechanism of action of LSECs in liver regeneration and liver fibrosis is expected to provide new therapeutic targets for the prevention and treatment of chronic liver diseases.
- endothelial cells /
- liver cirrhosis /
- liver regeneration

HTML全文

参考文献(19)

[1] WANG L, LIU X, ZHUANG H. Cellular mechanisms in liver fibrosis regression[J]. J Clin Hepatol, 2018, 34 (4) :862-866. (in Chinese) 王林, 刘学恩, 庄辉.多种细胞在肝纤维化逆转中的作用[J].临床肝胆病杂志, 2018, 34 (4) :862-866.

[2] WANG B, ZHAO L, FISH M, et al. Self-renewing diploid Axin2 (+) cells fuel homeostatic renewal of the liver[J]. Nature, 2015, 524 (7564) :180-185.

[3] RAFII S, BUTLER JM, DING BS. Angiocrine functions of organ-specific endothelial cells[J]. Nature, 2016, 529 (7586) :316-325.

[4] LEIBING T, GRAUD C, AUGUSTIN I, et al. Angiocrine Wnt signaling controls liver growth and metabolic maturation in mice[J]. Hepatology, 2018, 68 (2) :707-722.

[5] ROCHA AS, VIDAL V, MERTZ M, et al. The angiocrine factor rspondin3 is a key determinant of liver zonation[J]. Cell Rep, 2015, 13 (9) :1757-1764.

[6] DING BS, NOLAN DJ, BUTLER JM, et al. Inductive angiocrine signals from sinusoidal endothelium are required for liver regeneration[J]. Nature, 2010, 468 (7321) :310-315.

[7] LORENZ L, AXNICK J, BUSCHMANN T, et al. Mechanosensing by beta1 integrin induces angiocrine signals for liver growth and survival[J]. Nature, 2018, 562 (7725) :128-132.

[8] JIN WX, WANG B, ZHANG YL, et al. Effects of hepatic blood inflow on liver ultrastructure and regeneration after extensive liver resection in rats with cirrhosis[J]. Exp Ther Med, 2018, 16 (3) :2573-2583.

[9] DELEVE LD. Liver sinusoidal endothelial cells in hepatic fibrosis[J]. Hepatology, 2015, 61 (5) :1740-1746.

[10] XU M, WANG X, ZOU Y, et al. Key role of liver sinusoidal endothelial cells in liver fibrosis[J]. Biosci Trends, 2017, 11 (2) :163-168.

[11] DELEVE LD, WANG X, GUO Y. Sinusoidal endothelial cells prevent rat stellate cell activation and promote reversion to quiescence[J]. Hepatology, 2008, 48 (3) :920-930.

[12] XIE G, WANG X, WANG L, et al. Role of differentiation of liver sinusoidal endothelial cells in progression and regression of hepatic fibrosis in rats[J]. Gastroenterology, 2012, 142 (4) :918-927, e6.

[13] MARETTI-MIRA AC, WANG X, WANG L, et al. Incomplete differentiation of engrafted bone marrow endothelial progenitor cells initiates hepatic fibrosis in the rat[J]. Hepatology, 2019, 69 (3) :1259-1272.

[14] DUAN JL, RUAN B, YAN XC, et al. Endothelial Notch activation reshapes the angiocrine of sinusoidal endothelia to aggravate liver fibrosis and blunt regeneration in mice[J]. Hepatology, 2018, 68 (2) :677-690.

[15] DING BS, CAO Z, LIS R, et al. Divergent angiocrine signals from vascular niche balance liver regeneration and fibrosis[J]. Nature, 2014, 505 (7481) :97-102.

[16] CHAN LK, GERSTENLAUER M, KONUKIEWITZ B, et al. Epithelial NEMO/IKKgamma limits fibrosis and promotes regeneration during pancreatitis[J]. Gut, 2017, 66 (11) :1995-2007.

[17] NEESSE A, ELLENRIEDER V. NEMO-CXCL12/CXCR4 axis:A novel vantage point for antifibrotic therapies in chronic pancreatitis?[J]. Gut, 2017, 66 (2) :211-212.

[18] GRIFFITHS K, HABIEL DM, JAFFAR J, et al. Anti-fibrotic effects of CXCR4-targeting i-body AD-114 in preclinical models of pulmonary fibrosis[J]. Sci Rep, 2018, 8 (1) :3212.

[19] QIN L, QIN J, ZHEN X, et al. Curcumin protects against hepatic stellate cells activation and migration by inhibiting the CXCL12/CXCR4 biological axis in liver fibrosis:A study in vitro and in vivo[J]. Biomed Pharmacother, 2018, 101:599-607.

施引文献

资源附件(0)

访问统计