Mechanistic roles of oxidized low density lipoprotein receptor 1(LOX-1) in fibrotic diseases and its diagnostic and therapeutic implications

Fibrotic diseases are progressive disorders characterized by excessive extracellular matrix (ECM) accumulation, pathological tissue remodeling, progressive organ dysfunction, and increased mortality. Despite their substantial clinical burden, effective therapies capable of preventing, reversing or curing established fibrosis remain limited. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) has emerged as a potential molecular target in fibrotic diseases, although its contribution to fibrotic remodeling appears to vary across organs and disease contexts. This review summarizes current evidence on the involvement of LOX-1 in fibrotic remodeling across major organs, the potential utility of sLOX-1 as a component of multimarker panels for the detection and monitoring of fibrotic diseases, and emerging therapeutic strategies targeting LOX-1 in fibrosis. Experimental and clinical evidence suggests that LOX-1 is associated with fibrotic remodeling through its interconnected mechanisms involving oxidative stress, inflammation, endothelial and epithelial injury, fibroblast and myofibroblast activation, dysregulated TGF-β/SMAD and related signaling pathways, and altered ECM turnover. However, the strength and mechanistic specificity of evidence vary considerably among tissues, organs and disease models. Circulating soluble LOX-1 (sLOX-1) shows promise as a complementary biomarker alongside established markers in multimarker panels for assessing fibrosis, although its specificity and clinical utility for fibrosis remain uncertain. Several direct and indirect LOX-1-targeted therapeutic approaches are emerging; however, their antifibrotic efficacy, safety, and clinical applicability remain to be established. Overall, LOX-1 represents a promising but incompletely validated biomarker and therapeutic target in fibrotic diseases. Further cell and tissue-specific mechanistic studies, multi-omics and spatial investigations, biomarker validation, and well-designed clinical trials are needed to clarify its diagnostic, prognostic, and therapeutic utility and its potential role in individualized antifibrotic treatment.