Decorin as a dynamic regulator in fibrosis: Mechanisms, therapeutic potential and future challenges

Fibrosis is a pathological process commonly encountered in patients with rheumatic diseases, infections and other related conditions. Due to the lack of effective therapeutic strategies, it has been associated with up to 45% of deaths in industrialized countries. Therefore, profound understanding of the underlying mechanisms and development of novel therapeutic approaches for fibrosis is urgently needed. Decorin, a key member of the proteoglycan family, has been well validated as a potential anti-fibrotic substance in a series of preclinical studies, with the sequestration of transforming growth factor-β1 (TGF-β1) from its receptor being interpreted as the main mechanism. Additionally, accumulating evidence indicates that decorin not only acts as a reservoir of various pro-fibrotic cytokines, but also participates in the regulation of immune responses and extracellular matrix (ECM)-associated proteases, making it a much more promising but challenging molecule in fibrosis. Indeed, fibrosis represents a process in which tissue injury, immune responses and ECM accumulation are disorderly tangled together. Decorin has been found to play tissue barrier-protective, anti-fibrotic or pro-inflammatory roles in a stage-specific manner during the whole progression of fibrosis. Therefore, although decorin-based anti-fibrotic studies have emerged and gratifying outcomes have been shown, the non-negligible challenges remain in precisely utilizing the anti-fibrotic efficacy of decorin. In conclusion, this review highlights the stage-dependent roles and underlying mechanisms of decorin in fibrosis of commonly affected organs. It also explores the therapeutic potential and current challenges of decorin-based interventions, offering new insights into the development of innovative anti-fibrotic strategies.