PEX16介导的脂质沉积在糖尿病肾病足细胞凋亡中的作用及机制研究

脂质代谢异常导致的足细胞凋亡在早期糖尿病肾病（DN）病理进程中极为重要。本项目采用DIA蛋白质组学联合WGCNA生物信息学分析筛选出过氧化物酶体生物发生因子16（PEX16）是调控DN脂质代谢的关键因子。PEX16在过氧化物酶体生成中起到重要作用，但其在足细胞凋亡及DN中的作用尚未见报道。我们前期研究发现DN时PEX16水平与足细胞脂质沉积密切相关；经生物信息学分析预测GNPAT是其下游靶基因，可通过调控PPARα参与脂质代谢。据此我们提出：DN时PEX16表达下降，通过调控GNPAT抑制PPARα-ACOX1信号通路，导致足细胞脂质沉积，诱导足细胞凋亡。本项目在整体动物、细胞及分子水平研究PEX16在DN足细胞凋亡中的作用及其机制；在临床样本上对PEX16与DN患者的临床相关指标及分期进行相关性分析，为探寻DN肾小球硬化早期诊断和病情评估提供新思路，为发现药物治疗的靶标提供理论依据。

Podocyte apoptosis induced by abnormal lipids metabolism is extremely important in the pathology of early diabetic nephropathy (DN). Peroxisomal biogenesis factor 16 (PEX16) is screened as a key factor in regulating lipid metabolism of DN by using WGCNA bioinformatics combined with DIA proteomic analysis. Although PEX16 is involved in peroxisomal biogenesis, its molecular mechanisms underlying podocyte apoptosis and DN is not completely understood. Our previous study had found that the level of PEX16 is closely related with podocyte lipid deposition. GNPAT is predicted as a key downstream gene of PEX16 through bioinformatics combined with proteomic analysis, which participates in lipid metabolism through regulting PPARα. Therefore, we hypothesize that the decreased level of PEX16 may mediate GNPAT to inhibit the PPARα-ACOX1 signaling pathway, leading to lipid deposition, and finally promotes podocyte apoptosis in DN. This project is intended to elucidate the role and related molecular mechanism of PEX16 in podocyte apoptosis. Furthermore, correlation analysis will be conducted between PEX16 expression and the clinical index of DN patients with different stages. The findings will provide theoretical and experimental evidence for exploring the specific markers of early diagnosis, evaluation and therapy target of DN glomerulosclerosis.