HSPB1 alleviates acute-on-chronic liver failure via the P53/Bax pathway

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-07-24 DOI:10.1515/biol-2022-0919

Zhixiang Zhang, Jinwei Guo, Jincan Zhu

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引用次数: 0

Abstract

The mortality rate of acute-on-chronic liver failure (ACLF) remains significantly elevated; hence, this study aimed to investigate the impact of heat shock protein family B (small) member 1 (HSPB1) on ACLF in vivo and in vitro and the underlying mechanism. This study used the ACLF mouse model, and liver damage extent was studied employing Masson trichrome, hematoxylin and eosin (H&E), Sirius red staining, and serum biochemical indices. Similarly, hepatocyte injury in lipopolysaccharide (LPS)-induced L02 cells was evaluated using cell counting kit-8 assay, enzymatic activity, flow cytometry, and TUNEL assay, while the underlying mechanism was investigated using western blot. Results showed that the morphology of liver tissue in ACLF mice was changed and was characterized by cirrhosis, fibrosis, collagen fiber deposition, inflammatory cell infiltration, and elevated liver injury indices. Moreover, HSPB1 was upregulated in both ACLF patients and mice, where overexpressing HSPB1 was found to inhibit ACLF-induced liver damage. Similarly, the HSPB1 expression in LPS-treated L02 cell lines was also increased, where overexpressing HSPB1 was found to promote cell viability, inhibit liver injury-related enzyme activity, and suppress apoptosis. Mechanistic investigations revealed that HSPB1 was responsible for inhibiting p-P53 and Bax protein levels, where activated P53 counteracted HSPB1’s effects on cellular behaviors. In conclusion, HSPB1 attenuated ACLF-induced liver injury in vivo and inhibited LPS-induced hepatocyte damage in vitro, suggesting that HSPB1 may be a novel target for ACLF therapy.

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HSPB1 通过 P53/Bax 通路缓解急性-慢性肝衰竭

急性-慢性肝衰竭（ACLF）的死亡率仍然显著升高，因此，本研究旨在探讨热休克蛋白B家族（小）成员1（HSPB1）在体内和体外对ACLF的影响及其内在机制。本研究采用 ACLF 小鼠模型，通过 Masson 三色、苏木精和伊红（H&E）、天狼星红染色以及血清生化指标研究肝损伤程度。同样，利用细胞计数试剂盒-8测定法、酶活性、流式细胞术和TUNEL测定法评估了脂多糖（LPS）诱导的L02细胞的肝细胞损伤，并利用Western印迹法研究了其潜在机制。结果表明，ACLF小鼠肝组织形态发生改变，表现为肝硬化、纤维化、胶原纤维沉积、炎性细胞浸润和肝损伤指数升高。此外，HSPB1 在 ACLF 患者和小鼠中均上调，过表达 HSPB1 可抑制 ACLF 引起的肝损伤。同样，在经 LPS 处理的 L02 细胞系中，HSPB1 的表达也有所增加，过表达 HSPB1 可促进细胞活力、抑制肝损伤相关酶的活性并抑制细胞凋亡。机理研究发现，HSPB1 负责抑制 p-P53 和 Bax 蛋白水平，活化的 P53 可抵消 HSPB1 对细胞行为的影响。总之，HSPB1能减轻ACLF诱导的体内肝损伤，抑制LPS诱导的体外肝细胞损伤，这表明HSPB1可能是治疗ACLF的一个新靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.