Comprehensive analysis of pyroptosis-related gene signatures in renal fibrosis.

Background: Renal fibrosis is key histopathological lesion in chronic kidney disease progression. This study explored pyroptosis-related gene signatures, potential molecular pathways and chemicals, as well as immune infiltration in renal fibrosis.

Methods: Renal fibrosis datasets and pyroptosis-related genes were obtained and differentially expressed pyroptosis-related genes (DEPGs) were identified. Then functional enrichment analysis was performed and core DEPGs were screened by WGCNA and LASSO regression analysis. Subsequently, miRNA-core DEPG interactions and potential chemicals were established. Finally, immune cell subtype distribution was evaluated and the core DEPGs were externally validated.

Results: A total of 38 DEPGs were identified which were enriched in inflammatory- and immune-related pathways. Nine core DEPGs were identified and the risk core = (0.1003 × Bak1) + (0.0944 × Zbp1) + (0.0882 × Tlr2) + (0.0585 × Il18) + (0.0497 × Adora2b) + (0.0418 × Stat3) + (0.0325 × Icam1) + (0.0272 × Pycard) + (0.0132 × Epha2). Nine core DEPGs exhibited high sensitivity and specificity for predicting UUO occurrence. A total of 444 miRNA-core DEPG interactions were obtained and miR-124-3p, miR-92a-3p, and miR-6807-5p were identified as core miRNAs. Adenosine served as a potential chemical that directly bound to Adora2b. Immune cells, including naïve B cells, CD4 effector memory T cells, (plasmacytoid) dendritic cells, monocytes, and neutrophils were significantly enriched in fibrotic kidneys. Finally, the differential expression, temporal expression patterns, and clinical correlation with renal function of core DEPGs were externally validated.

Conclusions: This study sheds light on the novel pyroptosis-related gene signatures in renal fibrosis.