Hepatic stellate cells as key target in liver fibrosis.
Hepatic stellate cells as key target in liver fibrosis.
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DOI：
10.1016/j.addr.2017.05.007
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发表时间：
2017-11-01
影响因子：
16.1
通讯作者：
Hoshida Y
中科院分区：
文献类型：
--
作者：
Higashi T;Friedman SL;Hoshida Y
由慢性病毒和代谢紊乱引起的进行性肝纤维化，每年通过发展成肝硬变导致100多万人死亡，尽管到目前为止还没有抗肝纤维化治疗被批准。肝星状细胞的转分化(或“激活”)是分泌基质蛋白的肌成纤维细胞的主要细胞来源，是肝纤维化形成的主要驱动力。损伤的上皮细胞、纤维化的组织微环境、免疫和系统代谢失调、肠道生物失调和肝炎病毒产物的旁分泌信号可以直接或间接地诱导星状细胞的激活。异常的细胞内信号、表观遗传学变化和细胞应激反应是通过诱导星状细胞恢复失活状态、细胞衰老、细胞凋亡和/或免疫细胞清除而使星状细胞失活的候选靶点。针对细胞类型和靶点的药物干预以治疗性地诱导失活，将使更有效和毒性更低的精确抗纤维化治疗成为可能。
Progressive liver fibrosis, induced by chronic viral and metabolic disorders, leads to more than one million deaths annually via development of cirrhosis, although no antifibrotic therapy has been approved to date. Transdifferentiation (or “activation”) of hepatic stellate cells is the major cellular source of matrix protein-secreting myofibroblasts, the major driver of liver fibrogenesis. Paracrine signals from injured epithelial cells, fibrotic tissue microenvironment, immune and systemic metabolic dysregulation, enteric dysbiosis, and hepatitis viral products can directly or indirectly induce stellate cell activation. Dysregulated intracellular signaling, epigenetic changes, and cellular stress response represent candidate targets to deactivate stellate cells by inducing reversion to inactivated state, cellular senescence, apoptosis, and/or clearance by immune cells. Cell type- and target-specific pharmacological intervention to therapeutically induce the deactivation will enable more effective and less toxic precision antifibrotic therapies.
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DOI：
10.1039/c6ib00027d
发表时间：
2016-06-13
期刊：
Integrative biology : quantitative biosciences from nano to macro
影响因子：
--
作者：
Caliari SR;Perepelyuk M;Soulas EM;Lee GY;Wells RG;Burdick JA
通讯作者：
Burdick JA
DOI：
10.1073/pnas.0409722102
发表时间：
2005-03-01
影响因子：
11.1
作者：
Campbell, JS;Hughes, SD;Fausto, N
通讯作者：
Fausto, N
影响因子：
13.5
作者：
Bruschi, Francesca Virginia;Claudel, Thierry;Trauner, Michael
通讯作者：
Trauner, Michael
影响因子：
13.5
作者：
Aoyama, Tomonori;Paik, Yong-Han;Watanabe, Sumio;Laleu, Benoit;Gaggini, Francesca;Fioraso-Cartier, Laetitia;Molango, Sophie;Heitz, Freddy;Merlot, Cedric;Szyndralewiez, Cedric;Page, Patrick;Brenner, David A.
通讯作者：
Brenner, David A.
影响因子：
13.5
作者：
Anan, A;Baskin-Bey, ES;Gores, GJ
通讯作者：
Gores, GJ