文献类型：期刊文献

英文题名：Molecular mechanisms and targeted therapy of progranulin in metabolic diseases

作者：Wang, Xiaxia[1];Liang, Yonglin[1];Yang, Fan[2];Shi, Yangyang[1];Shao, Ruiwen[1];Jing, Ruge[1];Yang, Tong[1];Chu, Qiao[1];An, Dong[1];Zhou, Qi[1];Song, Jiayi[1];Chen, Haolan[3];Liu, Chun[4]

第一作者：王学香;王小霞

通信作者：Liang, YL[1];Liu, C[2]

机构：[1]Gansu Univ Chinese Med, Sch Basic Med, Lanzhou, Gansu, Peoples R China;[2]Gansu Univ Chinese Med, Sch Tradit Chinese & Western Med, Lanzhou, Gansu, Peoples R China;[3]Nanhu Community Hlth Ctr, TCM Internal Med Dept, Pinliang, Gansu, Peoples R China;[4]Gansu Univ Chinese Med, Lib, Lanzhou, Gansu, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Sch Basic Med, Lanzhou, Gansu, Peoples R China;[2]corresponding author), Gansu Univ Chinese Med, Lib, Lanzhou, Gansu, Peoples R China.|[10735]甘肃中医药大学;

年份：2025

卷号：16

外文期刊名：FRONTIERS IN ENDOCRINOLOGY

收录：;Scopus(收录号：2-s2.0-105003640465);WOS:【SCI-EXPANDED(收录号:WOS:001474136100001)】；

基金：The author(s) declare that financial support was received for the research and/or publication of this article. This study was supported by the National Natural Science Foundation of China (82460897) the Gansu Provincial Department of Education: Outstanding Research Student 'Innovation Star' Project (2025CXZX-905), and the Gansu Provincial Research Center for Traditional Chinese Medicine (zyzx-2024-zx01) and the Industrial Support Programme Project for Higher Education Institutions in Gansu Province (2021CYZC-03).

语种：英文

外文关键词：PGRN; metabolic diseases; inflammation; cartilage repair; bone homeostasis; targeted therapy

摘要：Progranulin (PGRN) is a secreted glycoprotein with cytokine-like properties, exerting tripartite mechanisms of inflammation suppression, tissue repair promotion, and metabolic regulation. This multifaceted functionality positions PGRN as a potential "multi-effect therapeutic strategy" for metabolic disorders characterised by cartilage degradation and imbalanced bone remodelling, potentially establishing it as a novel therapeutic target for such conditions. Osteoarthritis, rheumatoid arthritis, intervertebral disc degeneration, osteoporosis, periodontitis, and diabetes-related complications-representing the most prevalent metabolic diseases-currently lack effective treatments due to incomplete understanding of their precise pathogenic mechanisms. Recent studies have revealed that PGRN expression levels are closely associated with the onset and progression of these metabolic disorders. However, the exact regulatory role of PGRN in these diseases remains elusive, partly owing to its tissue-specific actions and context-dependent dual roles (anti-inflammatory vs. pro-inflammatory). In this review, we summarise the structure and functions of PGRN, explore its involvement in neurological disorders, immune-inflammatory diseases, and metabolic conditions, and specifically focus on its molecular mechanisms in metabolic diseases. Furthermore, we consolidate advances in targeting PGRN and the application of its engineered derivative, Atsttrin, in metabolic bone disorders. We also discuss potential unexplored mechanisms through which PGRN may exert influence within this field or other therapeutic domains. Collectively, this work aims to provide a new framework for elucidating PGRN's role in disease pathogenesis and advancing strategies for the prevention and treatment of metabolic disorders.