Phosphatidylinositol metabolism of the renal proximal tubule S3 segment is disturbed in response to diabetes

被引:9
作者
Rietjens, Rosalie G. J. [1 ,2 ,3 ]
Wang, Gangqi [1 ,2 ,3 ]
van der Velden, Anouk I. M. [1 ,2 ]
Koudijs, Angela [1 ,2 ]
Avramut, M. Cristina [2 ,4 ]
Kooijman, Sander [2 ,5 ]
Rensen, Patrick C. N. [2 ,5 ]
van der Vlag, Johan [6 ]
Rabelink, Ton J. [1 ,2 ,3 ]
Heijs, Bram [3 ,7 ]
van den Berg, Bernard M. [1 ,2 ,3 ]
机构
[1] Leiden Univ, Dept Internal Med Nephrol, Med Ctr, Leiden, Netherlands
[2] Leiden Univ, Einthoven Lab Vasc & Regenerat Med, Med Ctr, Leiden, Netherlands
[3] Leiden Univ, Novo Nordisk Fdn Ctr Stem Cell Med ReNEW, Med Ctr, Leiden, Netherlands
[4] Leiden Univ, Dept Cell & Chem Biol Electron Microscopy, Med Ctr, Leiden, Netherlands
[5] Leiden Univ, Dept Internal Med Endocrinol, Med Ctr, Leiden, Netherlands
[6] Radboud Univ Nijmegen, Dept Nephrol, Med Ctr, Nijmegen, Netherlands
[7] Leiden Univ, Ctr Prote & Metabol, Med Ctr, Leiden, Netherlands
关键词
MASS-SPECTROMETRY; NEPHROPATHY; DIAGNOSIS; BARRIER; INJURY; ACIDS;
D O I
10.1038/s41598-023-33442-2
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Diabetes is a main risk factor for kidney disease, causing diabetic nephropathy in close to half of all patients with diabetes. Metabolism has recently been identified to be decisive in cell fate decisions and repair. Here we used mass spectrometry imaging (MSI) to identify tissue specific metabolic dysregulation, in order to better understand early diabetes-induced metabolic changes of renal cell types. In our experimental diabetes mouse model, early glomerular glycocalyx barrier loss and systemic metabolic changes were observed. In addition, MSI targeted at small molecule metabolites and glycero(phospho)lipids exposed distinct changes upon diabetes in downstream nephron segments. Interestingly, the outer stripe of the outer medullar proximal tubular segment (PT_S3) demonstrated the most distinct response compared to other segments. Furthermore, phosphatidylinositol lipid metabolism was altered specifically in PT_S3, with one of the phosphatidylinositol fatty acid tails being exchanged from longer unsaturated fatty acids to shorter, more saturated fatty acids. In acute kidney injury, the PT_S3 segment and its metabolism are already recognized as important factors in kidney repair processes. The current study exposes early diabetes-induced changes in membrane lipid composition in this PT_S3 segment as a hitherto unrecognized culprit in the early renal response to diabetes.
引用
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页数:12
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