Pathological transcriptional retention of Cyp26b1 in perirenal adipose-derived stem cells contributes to MASLD progression.

IF 7.8 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Hepatology International Pub Date : 2026-10-01 Epub Date: 2026-06-29 DOI:10.1007/s12072-026-11118-z

Yannan Zhang, Zheng Li, Jinyu Sun, Changhao Xu, Min Gao, Hui Shen, Dongxu Hua, Qiyang Xie, Yi Xiao, Yuanjie Huang, Peng Li, Wei Sun, Xiangqing Kong

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引用次数: 0

Abstract

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent liver disorder linked to metabolic syndrome, but its extrahepatic drivers and persistence mechanisms remain unclear.

Methods: Transcriptomics was performed on adipose-derived stem cells (ADSCs) from distinct adipose depots in dynamic MASLD mouse models. A dietary reversal model was used to assess transcriptional retention. Candidate genes were identified via integrated DNA methylome and transcriptome analysis. Cyp26b1 function was tested by perirenal ADSCs-specific knockdown, and involved downstream mechanisms were investigated.

Results: Perirenal ADSCs exhibited an early dysregulated transcriptional signature in MASLD and retained high transcriptional retention after reversal. Multi-omics identified Cyp26b1 as a persistent, epigenetically regulated driver. Knockdown of Cyp26b1 in perirenal ADSCs attenuated MASLD progression, potentially by modulating the CCL3-CCR5 axis to alleviate hepatic steatosis and inflammation.

Conclusion: This study reveals an ADSC-mediated perirenal adipose-liver axis and establishes pathological "memory" in ADSCs as a perpetuating factor in MASLD. Transcriptional retention in perirenal ADSCs and its key regulator Cyp26b1 represent potential theoretical targets for exploring the mechanism and intervention of cellular "memory" in MASLD.

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肾周脂肪来源干细胞中Cyp26b1的病理性转录保留有助于MASLD的进展。

背景：代谢功能障碍相关脂肪变性肝病（MASLD）是一种与代谢综合征相关的常见肝脏疾病，但其肝外驱动因素和持续机制尚不清楚。方法：对动态MASLD小鼠模型中来自不同脂肪库的脂肪来源干细胞（ADSCs）进行转录组学研究。饮食逆转模型用于评估转录保留。候选基因通过整合DNA甲基组和转录组分析鉴定。通过肾周adscs特异性敲低检测Cyp26b1功能，并研究其下游机制。结果：肾周ADSCs在MASLD中表现出早期转录失调的特征，并在逆转后保持高转录保留。多组学鉴定Cyp26b1是一个持久的、表观遗传调控的驱动因素。在肾周ADSCs中，Cyp26b1的下调可能通过调节CCL3-CCR5轴来减轻肝脂肪变性和炎症，从而减轻MASLD的进展。结论：本研究揭示了adsc介导的肾周脂肪-肝轴，并在adsc中建立了病理“记忆”作为MASLD的延续因素。肾周ADSCs的转录保留及其关键调节因子Cyp26b1是探索MASLD细胞“记忆”机制和干预的潜在理论靶点。

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

Hepatology International 医学-胃肠肝病学

CiteScore

10.90

自引率

3.00%

发文量

167

审稿时长

6-12 weeks

期刊介绍： Hepatology International is the official journal of the Asian Pacific Association for the Study of the Liver (APASL). This is a peer-reviewed journal featuring articles written by clinicians, clinical researchers and basic scientists is dedicated to research and patient care issues in hepatology. This journal will focus mainly on new and emerging technologies, cutting-edge science and advances in liver and biliary disorders. Types of articles published: -Original Research Articles related to clinical care and basic research -Review Articles -Consensus guidelines for diagnosis and treatment -Clinical cases, images -Selected Author Summaries -Video Submissions