Differential expression of NEK7-NLRP3 inflammasome-related genes in systemic sclerosis dermal fibroblasts: a subtype-specific analysis.
TL;DR
Findings identify a subtype-specific pattern of inflammasome-related gene expression in SSc dermal fibroblasts and suggest a potential association with the fibrotic phenotype and further protein-level and functional studies are warranted.
Abstract
Purpose
This study investigated the expression of NEK7-NLRP3 inflammasome-related genes in dermal fibroblasts from patients with systemic sclerosis (SSc), focusing on limited (lSSc) and diffuse cutaneous (dSSc) subtypes and their association with skin fibrosis.
Methods
Dermal fibroblasts were obtained from patients with SSc and age-matched healthy controls. Messenger RNA expression of NEK7, NLRP3, ASC, caspase-1, IL-1β, IL-18, and COL1A1 was measured by real-time polymerase chain reaction.
Results
The cohort comprised 13 patients with SSc (mean age 53.8 ± 11.7 years, 69.2% female, 53.8% dSSc) and healthy controls. Modified Rodnan skin score (mRSS) and Medsger severity scores were significantly higher in dSSc than in lSSc (p < 0.05), and were strongly correlated (r = 0.893, p < 0.001). Overall expression of inflammasome-related genes did not differ significantly between the total SSc group and controls. However, subgroup analysis revealed a distinct molecular profile. NEK7 and IL-1β expression levels were significantly higher in lSSc fibroblasts than in dSSc fibroblasts (p = 0.01 and p = 0.015, respectively), while NLRP3 expression was increased in lSSc compared with controls (p = 0.01). Within the lSSc subgroup, IL-18 levels were inversely correlated with mRSS (r = -0.883, p = 0.020), and caspase-1 expression was negatively correlated with age (r = -0.928, p = 0.008).
Conclusion
These findings identify a subtype-specific pattern of inflammasome-related gene expression in SSc dermal fibroblasts and suggest a potential association with the fibrotic phenotype. Further protein-level and functional studies are warranted.