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논문분류	춘계학술대회 초록집
제목	Ceramide Mediates the Mitochondrial Dysfunction in Diabetic Kidney Disease
저자	Zijun Sun
출판정보	2025; 2025(1):
키워드	ceramide, mitochondrial dysfunction, diabetic kidney disease
초록	Cumulating evidences suggested the pathogenic role of phospholipid metabolism in diabetic kidney disease (DKD). The current study aimed to investigate the effect of ceramide (Cer) on lipid metabolism in the development of DKD. Streptozotocin combined with high-fat diet induced diabetes mice were divided into diabetes mice and control mice, and the changes of proteinuria and kidney injury were detected. Lipidomes and transcriptomic analysis was conducted on the kidney cortex of diabetes model mice and their litters of wild-type mice. Further, the differences in mitochondrial damage and apoptosis were compared between the two groups of mice. Compared with wild-type mice, urinary protein, renal tubulointerstitial injury, foot process fusion of podocyte, and renal inflammatory infiltration were aggravated in diabetic mice. Furthermore, the results showed that many lipid components, including triglycerides, sphingolipids, and phospholipids, were different between the two groups. According to the classification of ceramide with different fatty acid chain lengths, the contents of Cer (18:0), Cer (20:0), Cer (22:0) and Cer (t18:0) in the kidney tissues of diabetic mice were significantly increased compared with those of wild-type mice. Ultra-long chain ceramides such as Cer (23:0), Cer (25:0), and Cer (25:1) were significantly reduced. There were significant differences in ceramide synthase in proximal tubular epithelial cells between the two groups. Compared with wild-type mice, the renal cortical cleaved caspase-3/caspase-3 ratio of diabetic mice was significantly increased. Transcriptomic analysis showed that genes related to apoptosis and division/fusion of mitochondrial pathway cells. Compared with wild-type mice, Bax and MFF were significantly increased, while Bcl-2, MFN1 and MFN2 were significantly decreased in diabetic mice, and mitochondria became swollen and mitochondrial ridge was disorganized or partially disappeared. These results indicated that the renal ceramide profile of diabetic mice was changed and was closely related to mitochondrial dysfunction.
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