Clinical Pathology Department, Faculty of Medicine, Tanta University, El Geish Street, Tanta, 31527, El-Gharbia Governorate, Egypt.
Medical Biochemistry Department, Faculty of Medicine, Tanta University, Tanta, 31527, Egypt.
Mol Med. 2022 Dec 7;28(1):147. doi: 10.1186/s10020-022-00580-8.
Deregulated 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.
This 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.
RUBCN 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.
The 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.
最近，糖尿病中失调的自噬已成为许多实验研究的领域。糖尿病肾脏中的自噬受损会协调糖尿病肾病（DN）发病机制的每一步。本研究旨在评估三种自噬调节剂；RUBCN、mTOR 和 SESN2 作为 DN 进展的临床适用指标和 DN 的早期预测指标。
本回顾性研究包括 4 组 120 名参与者；G1：无白蛋白尿的糖尿病患者，G2：微量白蛋白尿的糖尿病患者，G3：大量白蛋白尿的糖尿病患者，G4：健康对照者。通过 RT-qPCR 检测 RUBCN 和 SESN2 基因的表达。通过 ELISA 定量检测 RUBCN、mTOR 和 SESN2 血清蛋白。
与对照组相比，糖尿病患者的 RUBCN mRNA 表达过度，其中 G3 最高，其次是 G2，然后是 G1；（9.04 ± 0.64、5.18 ± 0.73、1.94 ± 0.41，分别。P<0.001）。SESN2 mRNA 表达在 G3 中最低，其次是 G2，然后是 G1（0.1 ± 0.06、0.48 ± 0.11、0.78 ± 0.13，分别。P<0.001）。类似的血清 SESN2 平行降低观察到。与对照组相比，糖尿病患者的血清 RUBCN 和 mTOR 显著升高，且增加与白蛋白尿程度平行。RUBCN 表达、血清 RUBCN 和 mTOR 与白蛋白尿强烈相关（r=0.912、0.925 和 0.867，分别）。SESN2 表达和血清水平与白蛋白尿呈负相关（r=-0.897 和-0.828，分别）；（均 P<0.001）。回归分析表明，血清 RUBCN、mTOR、RUBCN 和 SESN2 mRNA 可成功预测 DN。
本研究证明了 RUBCN 和 mTOR 在 DN 中的过度表达和 SESN2 的下调。这三个标志物可用于临床预测 DN 并监测疾病进展。
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