ECM remodeling in hypothyroidism-associated MAFLD: mechanisms, clinical relevance, and therapeutic targets

作者：Tianzhen Wang, Liyun Duan, Beiying Zhao, Jingbin Zhang, Yongjiang Yu, Jinyue Zhao · 发表于：Frontiers in Immunology · 年份：2025 · DOI：10.3389/fimmu.2025.1639196 · 被引用次数：4 · 研究领域：Cardiovascular Function and Risk Factors、Endoplasmic Reticulum Stress and Disease、Liver Disease Diagnosis and Treatment

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a major chronic liver disease increasingly linked to endocrine and immunometabolic dysregulation. Hypothyroidism, both overt and subclinical, has emerged as a significant endocrine risk factor for MAFLD. Extracellular matrix (ECM) remodeling, a hallmark of fibrosis, represents a crucial but underexplored mediator in this process. This review highlights how altered thyroid hormone (TH) and thyroid-stimulating hormone (TSH) signaling promote ECM remodeling through metabolic, inflammatory, and fibrogenic pathways, with emphasis on hepatic stellate cell (HSC) activation and immune reshaping. We further summarize ECM-derived biomarkers and emerging therapeutic strategies, including THRβ agonists and ECM-targeted approaches.