Pharmacol Res. 2026 Sep 29:109647. doi: 10.1016/j.phrs.2026.109647. Online ahead of print.
ABSTRACT
Meteorin-like (Metrnl) is a newly discovered multifunctional secreted protein widely expressed in various tissues such as adipose tissue, skeletal muscle, and epithelial barrier tissues. This review systematically summarizes current knowledge of Metrnl, detailing its molecular characteristics, structure, cellular sources, inducers, receptors, and the complex signaling pathways and network. Metrnl has been identified as a pleiotropic protein with multiple effects, including enhancing insulin sensitivity, modulating lipid metabolism, promoting neurogenesis, reducing inflammation and oxidative stress, regulating tumor immunity, and potentiating angiogenesis and tissue repair. In metabolic and endocrine disorders, cardiovascular and cerebrovascular diseases, respiratory diseases, gastrointestinal diseases, skin diseases, autoimmune diseases, and nervous system diseases, and other pathological processes, the expression of Metrnl shows tissue-specific and disease stage-dependent changes, underscoring its potential as a biomarker or novel therapeutic target. However, the expression characteristics and biological functions of Metrnl in some diseases are controversial, and its tissue-specific role has not been fully elucidated. This review integrates clinical cohort studies and animal model results targeting Metrnl and its receptors. On this basis, we propose that Metrnl should be regarded as a stress-responsive immunometabolic molecule rather than a static disease biomarker. The research on targeted intervention in Metrnl is currently in the preclinical stage and has not yet progressed to clinical trials, and its clinical application value in specific diseases needs to be verified by large-scale stratified cohort analysis. This article aims to provide theoretical clues and novel insights for understanding Metrnl as a potential biomarker and therapeutic target.
PMID:42810631 | DOI:10.1016/j.phrs.2026.109647