2. Academic Validation
  3. TNAP-induced CD47 membrane expression enhances TGF-β1 conversion in liver fibrosis

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

  • Hepatol Commun. 2025 Sep 29;9(10):e0781. doi: 10.1097/HC9.0000000000000781.
Lei Gao 1,  Fengling Peng 2 3,  Peng Qi 2,  Hanqiu Zhang 4,  Hao Chi 5,  Liang Deng 6,  Xin Liang 7,  Min Sun 8,  Wenkun Ma 9,  Cheng Yang 2,  Qiang Liu 10,  Xiaoyu Wei 11,  Yongguo Li 2,  Jinqiu Zhao 2
Affiliations

Affiliations

  • 1 Department of Cardiovascular Medicine, Cardiovascular Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 2 Department of Infectious Disease, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 3 Department of Tuberculosis, Public Health Clinical Center of Chengdu, Chengdu, China.
  • 4 Department of Quantitative Health Sciences, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA.
  • 5 Clinical Medical College, Southwest Medical University, Sichuan, China.
  • 6 Department of Gastroenterology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 7 Department of Pathology, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, China.
  • 8 Health Management Center, The First Branch of the Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 9 James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, Ohio, USA.
  • 10 Department of Hepatological Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 11 Department of Infectious Disease, The Affiliated Yongchuan Hospital of Chongqing Medical University, Chongqing, China.
PMID: 41021282 DOI: 10.1097/HC9.0000000000000781
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.

Keywords

CD47; TGF-β1 conversion; TNAP; liver fibrosis.

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