Zhang Yiran, Piao Hai-Long, Chen Di
Key Laboratory of Phytochemistry and Natural Medicines, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Metabolites. 2024 Nov 20;14(11):641. doi: 10.3390/metabo14110641.
Diabetic kidney disease (DKD) is a major complication of diabetes leading to kidney failure. This study investigates lipid metabolism profiles of long-standing DKD (LDKD, diabetes duration > 10 years) by integrative analysis of available single-cell RNA sequencing and spatial multi-omics data (focusing on spatial continuity samples) from the Kidney Precision Medicine Project. Two injured cell types, an injured thick ascending limb (iTAL) and an injured proximal tubule (iPT), were identified and significantly elevated in LDKD samples. Both iTAL and iPT exhibit increased lipid metabolic and biosynthetic activities and decreased lipid and fatty acid oxidative processes compared to TAL/PT cells. Notably, compared to PT, iPT shows significant upregulation of specific injury and fibrosis-related genes, including and . Meanwhile, comparing iTAL to TAL, inflammatory-related genes such as and are significantly upregulated. Furthermore, spatial metabolomics analysis reveals regionally distributed clusters in the kidney and notably differentially expressed lipid metabolites, such as triglycerides, glycerophospholipids, and sphingolipids, particularly pronounced in the inner medullary regions. These findings provide an integrative description of the lipid metabolism landscape in LDKD, highlighting injury-associated cellular processes and potential molecular mechanisms.
糖尿病肾病（DKD）是导致肾衰竭的糖尿病主要并发症。本研究通过对肾脏精准医学项目中现有的单细胞RNA测序和空间多组学数据（聚焦于空间连续样本）进行综合分析，研究长期糖尿病肾病（LDKD，糖尿病病程>10年）的脂质代谢谱。鉴定出两种受损细胞类型，即受损的髓袢升支粗段（iTAL）和受损的近端小管（iPT），且在LDKD样本中显著增多。与TAL/PT细胞相比，iTAL和iPT均表现出脂质代谢和生物合成活性增加，脂质和脂肪酸氧化过程减少。值得注意的是，与PT相比，iPT显示出特定损伤和纤维化相关基因的显著上调，包括 和 。同时，将iTAL与TAL相比，诸如 和 等炎症相关基因显著上调。此外，空间代谢组学分析揭示了肾脏中区域分布的簇以及显著差异表达的脂质代谢物，如甘油三酯、甘油磷脂和鞘脂，在内髓区域尤为明显。这些发现提供了LDKD中脂质代谢格局的综合描述，突出了与损伤相关的细胞过程和潜在分子机制。
