Resistin in Tissue Remodeling and Fibrosis: A New Frontier.

Initially identified as a hormone linking obesity to insulin resistance, resistin is now recognized as a pleiotropic mediator whose cellular sources and biological functions differ substantially between humans and rodents. Beyond its established roles in metabolic dysfunction and inflammation, emerging evidence suggests that resistin may contribute to tissue remodeling and fibrosis in a context-dependent manner. This review critically synthesizes mechanistic, translational, and clinical evidence across the heart, liver, lung, and kidney. Reported interactions with candidate receptors or binding partners, including adenylyl cyclase-associated protein 1 (CAP1) and Toll-like receptor 4 (TLR4), link resistin-associated signaling to inflammatory, oxidative-stress, and profibrotic pathways that can influence fibroblast activation, hepatic stellate cell responses, extracellular matrix production, and structural tissue remodeling. However, the strength and nature of the available evidence differ markedly among organ systems. Direct profibrotic effects are most strongly supported in cardiac experimental models and selected hepatic systems, whereas pulmonary mechanistic evidence is derived largely from studies of other RELM/FIZZ family members, particularly RELMα/FIZZ1 and RELMβ/FIZZ2, rather than human resistin itself, and renal evidence remains predominantly associative. We, therefore, propose a mechanistic paradigm shift that expands, rather than replaces, the established inflammatory role of resistin. Within this framework, the "fibrotic switch" is presented as a unifying hypothesis whereby persistent resistin-associated signaling may couple chronic inflammatory and metabolic stress to progressive fibrogenic remodeling, requiring further organ-, species-, and cell-specific validation. Defining the relevant cellular sources, receptors, and causal pathways will be essential for evaluating resistin as a biomarker and potential therapeutic target in fibrotic disease.