肝脏代谢火花:肝星状细胞活化的代谢和表观遗传重编程及其对人类代谢性疾病的影响。

IF 6.8 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Yeon Jin Roh, Hyeonki Kim, Dong Wook Choi
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引用次数: 0

摘要

肝脏在代谢稳态中起着基础作用,将全身燃料利用与各种代谢疾病的进展结合起来。肝星状细胞(Hepatic stellate cells, hsc)是肝脏中一种重要的非实质细胞类型,对维持肝脏结构处于静止状态至关重要。然而,在慢性肝损伤或代谢应激时,造血干细胞被激活,导致过度的细胞外基质沉积和促纤维化信号,最终使它们成为肝脏病理的关键参与者。新出现的证据强调了代谢重编程和表观遗传调控在造血干细胞激活中的关键作用。造血干细胞的激活是由内在的燃料代谢重编程和来自微环境的外在代谢信号驱动的,而代谢中间体积极地重塑表观遗传景观,加强纤维化转录程序。在这篇综述中,我们总结了在理解代谢和表观遗传改变如何驱动hsc激活,从而形成维持纤维化的转录程序方面的最新进展,并讨论了针对人类代谢性疾病中这些相互关联的途径的潜在治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Metabolic Sparks in the Liver: Metabolic and Epigenetic Reprogramming in Hepatic Stellate Cells Activation and Its Implications for Human Metabolic Diseases.

The liver plays a fundamental role in metabolic homeostasis, integrating systemic fuel utilization with the progression of various metabolic diseases. Hepatic stellate cells (HSCs) are a key nonparenchymal cell type in the liver, which is essential for maintaining hepatic architecture in their quiescent state. However, upon chronic liver injury or metabolic stress, HSCs become activated, leading to excessive extracellular matrix deposition and pro-fibrotic signaling, ultimately positioning them as key players in liver pathology. Emerging evidence highlights the critical roles of metabolic reprogramming and epigenetic regulation in HSCs activation. HSCs activation is driven by both intrinsic fuel metabolism reprogramming and extrinsic metabolic cues from the microenvironment, while the metabolic intermediates actively reshape the epigenetic landscape, reinforcing fibrogenic transcriptional programs. In this review, we summarize recent advances in understanding how metabolic and epigenetic alterations drive HSCs activation, thereby shaping transcriptional programs that sustain fibrosis, and discuss potential therapeutic strategies to target these interconnected pathways in human metabolic diseases.

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来源期刊
Diabetes & Metabolism Journal
Diabetes & Metabolism Journal Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
10.40
自引率
6.80%
发文量
92
审稿时长
52 weeks
期刊介绍: The aims of the Diabetes & Metabolism Journal are to contribute to the cure of and education about diabetes mellitus, and the advancement of diabetology through the sharing of scientific information on the latest developments in diabetology among members of the Korean Diabetes Association and other international societies. The Journal publishes articles on basic and clinical studies, focusing on areas such as metabolism, epidemiology, pathogenesis, complications, and treatments relevant to diabetes mellitus. It also publishes articles covering obesity and cardiovascular disease. Articles on translational research and timely issues including ubiquitous care or new technology in the management of diabetes and metabolic disorders are welcome. In addition, genome research, meta-analysis, and randomized controlled studies are welcome for publication. The editorial board invites articles from international research or clinical study groups. Publication is determined by the editors and peer reviewers, who are experts in their specific fields of diabetology.
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