REDD1减轻胆汁淤积性肝纤维化,抑制PI3K/AKT/mTOR通路。

IF 3.1 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL
Frontiers in Medicine Pub Date : 2025-09-24 eCollection Date: 2025-01-01 DOI:10.3389/fmed.2025.1628260
Xiaonan Li, Xin Liu, Xinrui Shi, Zixu Li, Qizhi Shuai, Tingjuan Huang, Yun Liu, Junjie Ren
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引用次数: 0

摘要

肝纤维化是可逆的。胆汁淤积是引起肝纤维化的重要因素。然而,目前临床上尚无针对胆汁淤积性肝纤维化的有效抗纤维化药物。方法:采用小鼠肝组织胆管结扎法(BDL)进行mRNA测序,采用RT-qPCR筛选靶基因REDD1。采用免疫组化方法检测原发性胆道性胆管炎(PBC)患者肝组织中REDD1、CD68、α-SMA、PI3K/AKT/mTOR信号通路的表达。随后,腺病毒介导的REDD1经尾静脉转染小鼠肝组织,评价其治疗效果。结果:RNA测序显示,在bdl诱导的纤维化肝组织中,REDD1显著上调。PBC患者中,REDD1的表达与α-SMA和CD68呈正相关,提示其参与纤维形成。然而,组织和分子分析(α-SMA和胶原I)证实,过表达REDD1可改善bdl诱导的肝损伤,降低血清ALT/AST水平,减少胶原沉积,表明REDD1在肝纤维化中表现出代偿性升高。此外,PI3K/AKT/mTOR通路参与了REDD1对肝纤维化的改善。结论:这些发现强调了REDD1作为肝纤维化的潜在治疗靶点,可能通过调节PI3K/AKT/mTOR通路来减轻纤维化过程。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
REDD1 attenuates cholestatic liver fibrosis and suppresses PI3K/AKT/mTOR pathway.

Introduction: Liver fibrosis is reversible. Cholestasis is an important factor causing liver fibrosis. However, there are currently no effective anti-fibrotic drugs for cholestatic liver fibrosis in clinical practice.

Methods: mRNA sequencing was performed using mouse bile duct ligation (BDL) of liver tissue, and RT-qPCR was used to screen for the target gene REDD1. Immunohistochemistry was used to detect the expression of REDD1, CD68, α-SMA, and PI3K/AKT/mTOR signaling pathways in primary biliary cholangitis (PBC) patient liver tissue. Subsequently, adenovirus mediated REDD1 was transfected into mouse liver tissue via tail vein to evaluate its therapeutic effect.

Results: RNA sequencing revealed REDD1 was significantly upregulated in BDL-induced fibrotic liver tissue. REDD1 expression correlated positively with α-SMA and CD68 in PBC patients, suggesting its involvement in fibrogenesis. However, REDD1 overexpression ameliorated BDL-induced liver injury, reduced serum ALT/AST levels, and decreased collagen deposition, as evidenced by histological and molecular analyses (α-SMA and collagen I), indicating that REDD1 exhibited compensatory elevation in liver fibrosis. Additionally, PI3K/AKT/mTOR pathway was involved in the improvement of liver fibrosis by REDD1.

Conclusions: These findings highlight REDD1 as a potential therapeutic target for liver fibrosis, acting probably through modulation of the PI3K/AKT/mTOR pathway to mitigate fibrotic processes.

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来源期刊
Frontiers in Medicine
Frontiers in Medicine Medicine-General Medicine
CiteScore
5.10
自引率
5.10%
发文量
3710
审稿时长
12 weeks
期刊介绍: Frontiers in Medicine publishes rigorously peer-reviewed research linking basic research to clinical practice and patient care, as well as translating scientific advances into new therapies and diagnostic tools. Led by an outstanding Editorial Board of international experts, this multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide. In addition to papers that provide a link between basic research and clinical practice, a particular emphasis is given to studies that are directly relevant to patient care. In this spirit, the journal publishes the latest research results and medical knowledge that facilitate the translation of scientific advances into new therapies or diagnostic tools. The full listing of the Specialty Sections represented by Frontiers in Medicine is as listed below. As well as the established medical disciplines, Frontiers in Medicine is launching new sections that together will facilitate - the use of patient-reported outcomes under real world conditions - the exploitation of big data and the use of novel information and communication tools in the assessment of new medicines - the scientific bases for guidelines and decisions from regulatory authorities - access to medicinal products and medical devices worldwide - addressing the grand health challenges around the world
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