Clinical application of RUBCN/SESN2 mediated inhibition of autophagy as biomarkers of diabetic kidney disease

Molecular Medicine

Research Article

Mona M. Watany¹  Ahmed A. Elhadidy²  Hemat E. El-Horany³  Marwa M. Elhosary⁴ 

[1] Clinical Pathology Department, Faculty of Medicine, Tanta University, El Geish Street, 31527, Tanta, El-Gharbia Governorate, Egypt;Internal Medicine Department, Faculty of Medicine, Tanta University, 31527, Tanta, Egypt;Medical Biochemistry Department, Faculty of Medicine, Tanta University, 31527, Tanta, Egypt;Biochemistry Department, College of Medicine, Ha’il University, 55211, Ha’il, Saudi Arabia;Msc Immunology from Tanta Faculty of Science, 31527, Tanta, Egypt;

关键词: Diabetic nephropathy;    Autophagy;    Mammalian/mechanistic target of rapamycin (mTOR);    Rubicon (RUBCN);    Sestrin-2 (SESN2);    Insulin resistance, glycemic control;    Diabetic kidney disease;   

DOI  :  10.1186/s10020-022-00580-8

 received in 2022-07-04, accepted in 2022-11-26,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundDeregulated autophagy in diabetes has been a field of many experimental studies recently. Impaired autophagy in diabetic kidneys orchestrates every step of diabetic nephropathy (DN) pathogenesis. This study aimed to evaluate three autophagy regulators; RUBCN, mTOR, and SESN2 as clinically applicable indicators of DN progression and as early predictors of DN.MethodsThis retrospective study included 120 participants in 4 groups; G1: diabetic patients without albuminuria, G2: diabetic patients with microalbuminuria, G3: diabetic patients with macroalbuminuria and G4: healthy controls. RUBCN and SESN2 genes expression were tested by RT-qPCR. RUBCN, mTOR, and SESN2 serum proteins were quantitated by ELISA.ResultsRUBCN mRNA was over-expressed in diabetic patients relative to controls with the highest level found in G3 followed by G2 then G1; (9.04 ± 0.64, 5.18 ± 0.73, 1.94 ± 0.41 respectively. P < 0.001). SESN2 mRNA expression was at its lowest level in G3 followed by G2 then G1 (0.1 ± 0.06, 0.48 ± 0.11, 0.78 ± 0.13 respectively. P < 0.001). Similar parallel reduction in serum SENS2 was observed. Serum RUBCN and mTOR were significantly elevated in diabetic patients compared to controls, with the increase parallel to albuminuria degree. RUBCN expression, serum RUBCN and mTOR strongly correlated with albuminuria (r = 0.912, 0.925 and 0.867 respectively). SESN2 expression and serum level negatively correlated with albuminuria (r = − 0.897 and -0.828 respectively); (All p < 0.001). Regression analysis showed that serum RUBCN, mTOR, RUBCN and SESN2 mRNAs could successfully predict DN.ConclusionsThe study proves the overexpression of RUBCN and mTOR in DN and the down-expression of SESN2. The three markers can be clinically used to predict DN and to monitor disease progression.

【 授权许可】

CC BY   
© The Author(s) 2022

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