Zhang Dao-Hai, Wang Rui, Liu Liang, Zhang Peng, Zhao Jing-Hong, Liang Bo
Department of Nephrology, Key Laboratory for the Prevention and Treatment of Kidney Disease of Chongqing, Chongqing Clinical Research Center of Kidney and Urology Diseases, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, China.
Department of Massage, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China.
Clin Exp Nephrol. 2025 Jul 3. doi: 10.1007/s10157-025-02726-4.
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.
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.
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.
This study sheds light on the novel pyroptosis-related gene signatures in renal fibrosis.
肾纤维化是慢性肾脏病进展过程中的关键组织病理学病变。本研究探讨了肾纤维化中与焦亡相关的基因特征、潜在分子途径和化学物质，以及免疫浸润情况。
获取肾纤维化数据集和与焦亡相关的基因，鉴定差异表达的与焦亡相关基因（DEPGs）。然后进行功能富集分析，并通过加权基因共表达网络分析（WGCNA）和套索回归分析筛选核心DEPGs。随后，建立miRNA-核心DEPG相互作用和潜在化学物质。最后，评估免疫细胞亚型分布并对核心DEPGs进行外部验证。
共鉴定出38个DEPGs，它们富集于炎症和免疫相关途径。鉴定出9个核心DEPGs，风险核心 =（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）。9个核心DEPGs对预测单侧输尿管梗阻（UUO）的发生具有高敏感性和特异性。共获得444个miRNA-核心DEPG相互作用，miR-124-3p、miR-92a-3p和miR-6807-5p被鉴定为核心miRNA。腺苷作为一种潜在化学物质，直接与Adora2b结合。免疫细胞，包括幼稚B细胞、CD4效应记忆T细胞、（浆细胞样）树突状细胞、单核细胞和中性粒细胞在纤维化肾脏中显著富集。最后，对核心DEPGs的差异表达、时间表达模式以及与肾功能的临床相关性进行了外部验证。
本研究揭示了肾纤维化中与焦亡相关的新基因特征。
