TNAP-induced CD47 membrane expression enhances TGF-β1 conversion in liver fibrosis.

IF 5.6 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Hepatology Communications Pub Date : 2025-09-29 eCollection Date: 2025-10-01 DOI:10.1097/HC9.0000000000000781

Lei Gao, Fengling Peng, Peng Qi, Hanqiu Zhang, Hao Chi, Liang Deng, Xin Liang, Min Sun, Wenkun Ma, Cheng Yang, Qiang Liu, Xiaoyu Wei, Yongguo Li, Jinqiu Zhao

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引用次数: 0

Abstract

Background: Tissue-nonspecific alkaline phosphatase (TNAP) expression increases after liver injury, but its role in liver fibrosis remains unclear. This study investigated the effect of TNAP on liver fibrosis and its mechanism in regulating TGF-β1 signaling.

Methods: Human liver samples and a CCl4-induced liver fibrosis mouse model with adv-TNAP and a TNAP inhibitor (tetramisole, Tetra) were used to study the function of TNAP in liver fibrosis. Primary HSCs were used to study the mechanism of TNAP in regulating the TGF-β1 signal.

Results: Elevated TNAP expression was observed in human and murine fibrotic liver tissues, correlating with increased fibrotic markers. In vivo experiments using TNAP overexpression and inhibition in a CCl4-induced liver fibrosis mouse model demonstrated that TNAP exacerbated, while its inhibition alleviated, liver fibrosis. In vitro studies revealed that TNAP regulated TGF-β1 conversion and HSCs activation through the TGF-β1/SMAD pathway. TNAP facilitated TGF-β1 conversion by promoting the interaction between CD47 and thrombospondin-1 (TSP1). Membrane expression of CD47 modulated by TNAP might contribute to the binding effect of CD47 and TSP1.

Conclusions: TNAP plays a critical regulatory role in TGF-β1-mediated liver fibrosis, probably by promoting the binding of CD47/TSP1. Targeting TNAP-mediated pathways may offer new therapeutic strategies for liver fibrosis.

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tnap诱导的CD47膜表达增强TGF-β1在肝纤维化中的转化。

背景：组织非特异性碱性磷酸酶（TNAP）在肝损伤后表达增加，但其在肝纤维化中的作用尚不清楚。本研究探讨TNAP对肝纤维化的影响及其调控TGF-β1信号通路的机制。方法：采用adv-TNAP和TNAP抑制剂（四曲咪唑，Tetra）建立ccl4诱导肝纤维化小鼠模型，研究TNAP在肝纤维化中的作用。利用原代hsc研究TNAP调控TGF-β1信号的机制。结果：人类和小鼠纤维化肝组织中TNAP表达升高，与纤维化标志物升高相关。在ccl4诱导的肝纤维化小鼠模型中，TNAP过表达和抑制的体内实验表明，TNAP加重了肝纤维化，而其抑制则减轻了肝纤维化。体外研究发现，TNAP通过TGF-β1/SMAD通路调控TGF-β1转化和hsc活化。TNAP通过促进CD47与血小板反应蛋白-1 （TSP1）的相互作用促进TGF-β1转化。TNAP调节CD47的膜表达可能参与了CD47与TSP1的结合作用。结论：TNAP可能通过促进CD47/TSP1的结合，在TGF-β1介导的肝纤维化中起关键调节作用。靶向tnap介导的途径可能为肝纤维化提供新的治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Hepatology Communications GASTROENTEROLOGY & HEPATOLOGY-

CiteScore

8.00

自引率

2.00%

发文量

248

审稿时长

8 weeks

期刊介绍： Hepatology Communications is a peer-reviewed, online-only, open access journal for fast dissemination of high quality basic, translational, and clinical research in hepatology. Hepatology Communications maintains high standard and rigorous peer review. Because of its open access nature, authors retain the copyright to their works, all articles are immediately available and free to read and share, and it is fully compliant with funder and institutional mandates. The journal is committed to fast publication and author satisfaction.