Title : Transcriptomic profiling of Mono Sodium Urate (MSU) -induced inflammation in a mouse model of acute gout
Abstract:
Gout is the most common inflammatory arthritis, caused by the deposition of Mono Sodium Urate (MSU) crystals in joints, leading to acute flares characterized by intense pain and inflammation. This study aimed to investigate the molecular mechanisms underlying MSU-induced inflammation in gout by reanalyzing RNA-seq data from an acute mouse model. RNA was isolated from MSU-injected and control mouse ankle joints, and transcriptomic analysis was performed using RNA-seq analysis. Differential gene expression analysis identified significantly up-regulated genes, such as Ptx3, Il1b, Nlrp3, Hdc, Ccl7, and Toll-like receptors, many of which are key inflammatory cytokines, chemokines, and their receptors as well as mediators involved in histamine biosynthesis. Among the significantly down-regulated genes, such as Col8a2, Lgals12, and Adam33, some are associated with structural and metabolic pathways. Additionally, gene ontology and pathway enrichment analyses provided insights into biological processes and molecular pathways affected by MSU-induced inflammation. Importantly, the analysis also revealed that MSU-induced inflammation disrupts tissue repair mechanisms, as shown by the downregulation of wound healing and extracellular matrix organization genes, including Vegfb, Fgf1, Vwf, Fzd7, Plat, Clec10a, CD151, F3, and Alox5. Functional enrichment analysis further confirmed suppression of biological processes related to tissue remodeling and activation of innate immune responses. These results suggest that in addition to promoting acute inflammation, MSU crystals inhibit resolution and repair pathways, thereby potentially contributing to chronic joint damage in gout. These findings offer further insights into the pathophysiology of gout and hold the potential to inform future therapeutic strategies aimed at both suppressing inflammation and promoting tissue repair.
