Department of Nephrology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China.
Institute of Immunology, School of Medicine, Zhejiang University, Hangzhou, 310058, China.
BMC Nephrol. 2024 Feb 27;25(1):72. doi: 10.1186/s12882-024-03505-1.
Diabetic nephropathy (DN) and atherosclerosis (AS) are prevalent and severe complications associated with diabetes, exhibiting lesions in the basement membrane, an essential component found within the glomerulus, tubules, and arteries. These lesions contribute significantly to the progression of both diseases, however, the precise underlying mechanisms, as well as any potential shared pathogenic processes between them, remain elusive.
Our study analyzed transcriptomic profiles from DN and AS patients, sourced from the Gene Expression Omnibus database. A combination of integrated bioinformatics approaches and machine learning models were deployed to identify crucial genes connected to basement membrane lesions in both conditions. The role of integrin subunit alpha M (ITGAM) was further explored using immune infiltration analysis and genetic correlation studies. Single-cell sequencing analysis was employed to delineate the expression of ITGAM across different cell types within DN and AS tissues.
Our analyses identified ITGAM as a key gene involved in basement membrane alterations and revealed its primary expression within macrophages in both DN and AS. ITGAM was significantly correlated with tissue immune infiltration within these diseases. Furthermore, the expression of genes encoding core components of the basement membrane was influenced by the expression level of ITGAM.
Our findings suggest that macrophages may contribute to basement membrane lesions in DN and AS through the action of ITGAM. Moreover, therapeutic strategies that target ITGAM may offer potential avenues to mitigate basement membrane lesions in these two diabetes-related complications.
糖尿病肾病（DN）和动脉粥样硬化（AS）是糖尿病常见且严重的并发症，它们在肾脏肾小球、肾小管和动脉的基底膜中出现病变。这些病变是两种疾病进展的重要原因，但它们的确切潜在机制以及它们之间可能存在的共同致病过程仍不清楚。
我们的研究分析了来自基因表达综合数据库（GEO）的 DN 和 AS 患者的转录组谱。我们采用了综合生物信息学方法和机器学习模型的组合，来识别与两种情况下基底膜病变相关的关键基因。进一步通过免疫浸润分析和遗传相关性研究来探索整合素亚基α M（ITGAM）的作用。我们还利用单细胞测序分析来描绘 ITGAM 在 DN 和 AS 组织中不同细胞类型中的表达情况。
我们的分析确定 ITGAM 是一个与基底膜改变相关的关键基因，并揭示了它在 DN 和 AS 中的主要表达是在巨噬细胞中。ITGAM 与这些疾病中的组织免疫浸润显著相关。此外，基底膜核心成分编码基因的表达受 ITGAM 表达水平的影响。
我们的研究结果表明，巨噬细胞可能通过 ITGAM 的作用导致 DN 和 AS 中的基底膜病变。此外，针对 ITGAM 的治疗策略可能为减轻这两种与糖尿病相关的并发症中的基底膜病变提供潜在途径。
