Sitagliptin Ameliorates Renal Tubular Injury in Diabetic Kidney Disease via STAT3-Dependent Mitochondrial Homeostasis Through SDF-1α/CXCR4 Pathway

2019 ◽  
Author(s):  
Qunzi Zhang ◽  
Li He ◽  
Feng Liu ◽  
Jian Guan ◽  
Yang Dong ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Tubular Injury ◽  
Diabetic Kidney ◽  
Mitochondrial Homeostasis ◽  
Renal Tubular

scholarly journals Role of p53/miR-155-5p/sirt1 loop in renal tubular injury of diabetic kidney disease

2018 ◽  
Vol 16 (1) ◽  
Author(s):  
Yue Wang ◽  
Zong-ji Zheng ◽  
Yi-jie Jia ◽  
Yan-lin Yang ◽  
Yao-ming Xue
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Tubular Injury ◽  
Diabetic Kidney ◽  
Renal Tubular

scholarly journals Non-Albumin Proteinuria (NAP) as a Complementary Marker for Diabetic Kidney Disease (DKD)

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 224
Author(s):  
Jaehyun Bae ◽  
Young Jun Won ◽  
Byung-Wan Lee
Keyword(s):  
Kidney Disease ◽  
Filtration Rate ◽  
Diabetic Kidney Disease ◽  
Estimated Glomerular Filtration Rate ◽  
Early Stage ◽  
Screening Tools ◽  
Tubular Injury ◽  
Current Standard ◽  
Diabetic Kidney ◽  
Wide Range

Diabetic kidney disease (DKD) is one of the most common forms of chronic kidney disease. Its pathogenic mechanism is complex, and it can affect entire structures of the kidney. However, conventional approaches to early stage DKD have focused on changes to the glomerulus. Current standard screening tools for DKD, albuminuria, and estimated glomerular filtration rate are insufficient to reflect early tubular injury. Therefore, many tubular biomarkers have been suggested. Non-albumin proteinuria (NAP) contains a wide range of tubular biomarkers and is convenient to measure. We reviewed the clinical meanings of NAP and its significance as a marker for early stage DKD.

Ectopic lipid accumulation: potential role in tubular injury and inflammation in diabetic kidney disease

2018 ◽  
Vol 132 (22) ◽  
pp. 2407-2422 ◽  
Author(s):  
Wenxia Yang ◽  
Ying Luo ◽  
Shikun Yang ◽  
Mengru Zeng ◽  
Shumin Zhang ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Lipid Accumulation ◽  
Diabetic Kidney Disease ◽  
Mononuclear Cells ◽  
Regulatory Element ◽  
Tubular Damage ◽  
Tubular Injury ◽  
Diabetic Kidney ◽  
Tnf Α ◽  
Significant Difference

Emerging studies suggest that lipid accumulates in the kidneys during diabetic kidney disease (DKD). However, the correlation between ectopic lipid accumulation with tubular damage has not been thoroughly elucidated to date. Using Oil Red staining, lipid accumulation was observed in the kidneys of type 2 DKD patients (classes II–III) and db/db mice compared with the control and was predominantly located in the proximal tubular compartment. Immunohistochemistry (IHC) staining showed that the intensity of adipose differentiation related protein (ADRP) and sterol regulatory element binding protein-1 (SREBP-1) was clearly up-regulated, which was positively correlated with the tubulointerstitial damage score and inflammation. Furthermore, the urine ADRP content significantly increased in DKD patients compared with the control, which positively correlated with abnormal lipid metabolism, serum creatinine, urine N-acetyl-β-glucosaminidase (NAG), albumin excretion (albumin-to-creatinine ratio (ACR)), and tumor necrosis factor-α (TNF-α) expression. However, there was no significant difference observed in plasma ADRP levels. In addition, the expression of SREBP-1 protein was dramatically increased in peripheral blood mononuclear cells (PBMCs) isolated from DKD patients, which was also tightly correlated with urine NAG, ACR, and TNF-α levels. In vitro studies demonstrated increased ADRP and SREBP-1 expression accompanied by lipid accumulation in HK-2 cells cultured in high glucose (HG). HG induced high levels of TNF-α expression, which was partially blocked by transfection of ADRP siRNA or SREBP-1 siRNA. These data indicated that ADRP and SREBP-1 are crucial factors that mediate lipid accumulation with tubular damage and inflammation in DKD, and ectopic lipid accumulation may serve as a novel therapeutic target for amelioration of tubular injury in DKD.

scholarly journals 20(S)-Ginsenoside Rg3 Protects Kidney from Diabetic Kidney Disease via Renal Inflammation Depression in Diabetic Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Tong Zhou ◽  
Lin Sun ◽  
Shuo Yang ◽  
You Lv ◽  
Yue Cao ◽  
...  
Keyword(s):  
Treatment Group ◽  
Kidney Disease ◽  
Cell Apoptosis ◽  
Diabetic Kidney Disease ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Renal Tubular Cell ◽  
Ginsenoside Rg3 ◽  
Diabetic Kidney ◽  
Renal Tubular

20(S)-Ginsenoside Rg3 (20(S)-Rg3) has been shown to induce apoptosis by interfering with several signaling pathways. Furthermore, it has been reported to have anticancer and antidiabetic effects. In order to detect the protective effect of 20(S)-Rg3 on diabetic kidney disease (DKD), diabetic rat models which were established by administering high-sugar, high-fat diet combined with intraperitoneal injection of streptozotocin (STZ), and age-matched wild-type (WT) rat were given 20(S)-Rg3 for 12 weeks, with three groups: control group (normal adult rats with saline), diabetic group (diabetic rats with saline), and 20(S)-Rg3 treatment group (diabetic rats with 20(S)-Rg3 (10 mg/kg body weight/day)). The biochemical indicators and the changes in glomerular basement membrane and mesangial matrix were detected. TUNEL staining was used to detect glomerular and renal tubular cell apoptosis. Immunohistochemical staining was used to detect the expression of fibrosis factors and inflammation factors in rat kidney tissues. Through periodic acid-Schiff staining, we observed that the change in renal histology was improved and renal tubular epithelial cell apoptosis decreased significantly by treatment with 20(S)-Rg3. Plus, the urine protein decreased in the rats with the 20(S)-Rg3 treatment. Fasting blood glucose, creatinine, total cholesterol, and triglyceride levels in the 20(S)-Rg3 treatment group were all lower than those in the diabetic group. Mechanistically, 20(S)-Rg3 dramatically downregulated the expression of TGF-β1, NF-κB65, and TNF-α in the kidney. These resulted in a significant prevention of renal damage from the inflammation. The results of the current study suggest that 20(S)-Rg3 could potentially be used as a novel treatment against DKD.

scholarly journals Effects of Pentoxifylline on Soluble Klotho Concentrations and Renal Tubular Cell Expression in Diabetic Kidney Disease

Diabetes Care ◽  
2018 ◽  
Vol 41 (8) ◽  
pp. 1817-1820 ◽  
Author(s):  
Juan F. Navarro-González ◽  
María Dolores Sánchez-Niño ◽  
Javier Donate-Correa ◽  
Ernesto Martín-Núñez ◽  
Carla Ferri ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Tubular Cell ◽  
Renal Tubular Cell ◽  
Diabetic Kidney ◽  
Renal Tubular ◽  
Cell Expression

scholarly journals Ginkgo Biloba Extract EGB761 Ameliorates the Extracellular Matrix Accumulation and Mesenchymal Transformation of Renal Tubules in Diabetic Kidney Disease by Inhibiting Endoplasmic Reticulum Stress

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Jiarui Han ◽  
Xinxin Pang ◽  
Xiujie Shi ◽  
Yage Zhang ◽  
Zining Peng ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Endoplasmic Reticulum ◽  
Kidney Disease ◽  
Endoplasmic Reticulum Stress ◽  
Ginkgo Biloba ◽  
Diabetic Kidney Disease ◽  
Ginkgo Biloba Extract ◽  
Collagen Iv ◽  
Diabetic Kidney ◽  
Renal Tubular

The study is aimed at investigating the effects of Ginkgo biloba extract EGB761 on renal tubular damage and endoplasmic reticulum stress (ERS) in diabetic kidney disease (DKD). A total of 50 C57BL/6 N mice were randomly divided into the normal group, DKD group, DKD+EGB761 group (36 mg/kg), and DKD+4-phenylbutyrate (4-PBA) group (1 g/kg). The DKD model was replicated by high-fat diet combined with intraperitoneal injection of streptozotocin (STZ). Renal tubular epithelial cells (HK-2) were divided into the control group, high-glucose group (30 mmol/L), EGB761 group (40 mg/L, 20 mg/L, 10 mg/L), TM group, and TM+4-PBA group. After 8 weeks of administration, expressions of serum creatinine (Scr), blood urea nitrogen (BUN), 24 h urinary protein (24 h Pro), fasting blood glucose (FBG), β2-microglobulin (β2-MG), and retinol binding protein 4 (RBP4) of mice were tested. The pathological changes of renal tissue were observed. The expressions of extracellular matrix (ECM) accumulation and epithelial-mesenchymal transition (EMT) markers α-smooth muscle actin (α-SMA), E-cadherin, fibronectin, and collagen IV, as well as the ERS markers GRP78 and ATF6, were tested by Western blot, qPCR, immunohistochemistry, or immunofluorescence. EGB761 could decrease the Scr, BUN, 24 h Pro, and FBG levels in the DKD group, alleviate renal pathological injury, decrease urine β2-MG, RBP4 levels, and decrease the expression of α-SMA, collagen IV, fibronectin, and GRP78, as well as ATF6, while increase the expression of E-cadherin. These findings demonstrate that EGB761 can improve renal function, reduce tubular injury, and ameliorate ECM accumulation and EMT in DKD kidney tubules, and the mechanism may be related to the inhibition of ERS.

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