scholarly journals Intercellular transmission of endoplasmic reticulum stress through gap junction targeted by microRNAs as a key step of diabetic kidney diseases?

2021 ◽  
Vol 9 (10) ◽  
pp. 827-827
Author(s):  
Mitsuo Kato
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Gap Junction ◽  
Kidney Diseases ◽  
Diabetic Kidney

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.

scholarly journals CaMKII as a pathological mediator of ER stress, oxidative stress, and mitochondrial dysfunction in a murine model of nephronophthisis

2016 ◽  
Vol 310 (11) ◽  
pp. F1414-F1422 ◽  
Author(s):  
Christina Bracken ◽  
Philippe Beauverger ◽  
Olivier Duclos ◽  
Ryan J. Russo ◽  
Kelly A. Rogers ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Oxidative Damage ◽  
Molecular Mechanisms ◽  
Kidney Diseases ◽  
Cystic Kidney ◽  
Effective Inhibition ◽  
Stress Oxidative

Polycystic kidney diseases (PKDs) are genetic diseases characterized by renal cyst formation with increased cell proliferation, apoptosis, and transition to a secretory phenotype at the expense of terminal differentiation. Despite recent progress in understanding PKD pathogenesis and the emergence of potential therapies, the key molecular mechanisms promoting cystogenesis are not well understood. Here, we demonstrate that mechanisms including endoplasmic reticulum stress, oxidative damage, and compromised mitochondrial function all contribute to nephronophthisis-associated PKD. Ca2+/calmodulin-dependent protein kinase II (CaMKII) is emerging as a critical mediator of these cellular processes. Therefore, we reasoned that pharmacological targeting of CaMKII may translate into effective inhibition of PKD in jck mice. Our data demonstrate that CaMKII is activated within cystic kidney epithelia in jck mice. Blockade of CaMKII with a selective inhibitor results in effective inhibition of PKD in jck mice. Mechanistic experiments in vitro and in vivo demonstrated that CaMKII inhibition relieves endoplasmic reticulum stress and oxidative damage and improves mitochondrial integrity and membrane potential. Taken together, our data support CaMKII inhibition as a new and effective therapeutic avenue for the treatment of cystic diseases.

scholarly journals Expression of Serum GRP78 and CHOP in Endoplasmic Reticulum Stress Pathways of Chinese Type 2 Diabetic Kidney Disease Patients

2020 ◽  
Author(s):  
Ning Ma ◽  
Ning Xu ◽  
Dong Yin ◽  
Ping Zheng ◽  
Weiwei Liu ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Uric Acid ◽  
Kidney Disease ◽  
Endoplasmic Reticulum Stress ◽  
Serum Uric Acid ◽  
Diabetic Kidney Disease ◽  
Serum Levels ◽  
Chinese Patients ◽  
Diabetic Kidney

Abstract Background: The kidney has a rich endoplasmic reticulum system. A close relationship exists between endoplasmic reticulum stress (ERS) and diabetic kidney disease (DKD). The current study aimed to investigate serum glucose-regulated protein 78 (GRP78) as well as CCAAT/enhancer binding protein homologous protein (CHOP) concentrations in type 2 diabetes mellitus (T2DM) Chinese patients, especially those with microalbuminuria. Methods: We evaluated the relationships between serum GRP78 or CHOP levels and DKD. We recruited 67 patients with T2DM and 63 control subjects. We determined serum GRP78 and CHOP concentrations by ELISA, collected anthropometric data, and measured biochemical parameters in a clinical laboratory. Results: Compared with control groups, Chinese T2DM patients showed decreased serum levels of GRP78 [0.21 (0.16–0.24) vs. 0.16 (0.16–0.19) ng/mL, p < 0.01] and CHOP [3.8 (3.0–5.5) vs. 5.5 (3.7–7.9) ng/mL, p < 0.01]. Reduction in GRP78 and CHOP serum levels was more pronounced in patients with more severe categories of microalbuminuria. Amounts of serum GRP78 correlated directly with serum fasting c-peptide, cystatin-c (cys-c), creatinine (Cr), blood urea nitrogen (BUN), and uric acid, and inversely with glomerular filtration rates. Serum CHOP level was positively correlated with age, Cr, BUN, cys-c, urinary microalbumin/creatinine (UmALB/Cr), and eGFR. Serum GRP78 was predicted independently by Cr, BUN, serum uric acid, eGFR, and cys-c, while CHOP depended on age, Cr, BUN, serum uric acid, eGFR, UmALB/Cr, and cys-c. After controlling for confounding factors, GRP78 and CHOP expression was significantly associated with DKD (binary logistic regression, p < 0.01). Conclusions: T2DM patients showed increased serum GRP78 and CHOP concentrations. Receiver operating characteristic (ROC) areas under the curve for predicting DKD based on GRP78 and CHOP were 0.686 [95% CI: 0.558–0.813] and 0.670[0.524–0.816], respectively.

scholarly journals Endoplasmic reticulum stress and monogenic kidney diseases in precision nephrology

2018 ◽  
Vol 34 (9) ◽  
pp. 1493-1500 ◽  
Author(s):  
Sun-Ji Park ◽  
Yeawon Kim ◽  
Ying Maggie Chen
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Kidney Diseases

scholarly journals Expression of Serum GRP78 and CHOP in Endoplasmic Reticulum Stress Pathways of Chinese Type 2 Diabetic Kidney Disease Patients

2020 ◽  
Author(s):  
Ning Ma ◽  
Ning Xu ◽  
Dong Yin ◽  
Ping Zheng ◽  
Weiwei Liu ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Uric Acid ◽  
Kidney Disease ◽  
Endoplasmic Reticulum Stress ◽  
Serum Uric Acid ◽  
Diabetic Kidney Disease ◽  
Serum Levels ◽  
Chinese Patients ◽  
Diabetic Kidney

Abstract Background The kidney has a rich endoplasmic reticulum system. A close relationship exists between endoplasmic reticulum stress (ERS) and diabetic kidney disease (DKD). The current study aimed to investigate serum glucose-regulated protein 78 (GRP78) as well as CCAAT/enhancer binding protein homologous protein (CHOP) concentrations in type 2 diabetes mellitus (T2DM) Chinese patients, especially those with microalbuminuria. Methods We evaluated the relationships between serum GRP78 or CHOP levels and DKD. We recruited 67 patients with T2DM and 63 control subjects. We determined serum GRP78 and CHOP concentrations by ELISA, collected anthropometric data, and measured biochemical parameters in a clinical laboratory. Results Compared with control groups, Chinese T2DM patients showed decreased serum levels of GRP78 [0.21 (0.16–0.24) vs. 0.16 (0.16–0.19) ng/mL, p < 0.01] and CHOP [3.8 (3.0–5.5) vs. 5.5 (3.7–7.9) ng/mL, p < 0.01]. Reduction in GRP78 and CHOP serum levels was more pronounced in patients with more severe categories of microalbuminuria. Amounts of serum GRP78 correlated directly with serum fasting c-peptide, cystatin-c (cys-c), creatinine (Cr), blood urea nitrogen (BUN), and uric acid, and inversely with glomerular filtration rates. Serum CHOP level was positively correlated with age, Cr, BUN, cys-c, urinary microalbumin/creatinine (UmALB/Cr), and eGFR. Serum GRP78 was predicted independently by Cr, BUN, serum uric acid, eGFR, and cys-c, while CHOP depended on age, Cr, BUN, serum uric acid, eGFR, UmALB/Cr, and cys-c. After controlling for confounding factors, GRP78 and CHOP expression was significantly associated with DKD (binary logistic regression, p < 0.01). Conclusions T2DM patients showed increased serum GRP78 and CHOP concentrations. Receiver operating characteristic (ROC) areas under the curve for predicting DKD based on GRP78 and CHOP were 0.686 [95% CI: 0.558–0.813] and 0.670[0.524–0.816], respectively.

scholarly journals The AGE receptor, OST48 drives podocyte foot process effacement and basement membrane expansion in experimental diabetic kidney disease via promotion of endoplasmic reticulum stress

2019 ◽  
Author(s):  
Aowen Zhuang ◽  
Felicia YT Yap ◽  
Domenica McCarthy ◽  
Sally A. Penfold ◽  
Karly C. Sourris ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Kidney Disease ◽  
Endoplasmic Reticulum Stress ◽  
Advanced Glycation End Products ◽  
Diabetic Kidney Disease ◽  
Advanced Glycation ◽  
Diabetic Kidney ◽  
Glycation End Products ◽  
End Products ◽  
Foot Process

AbstractThe accumulation of advanced glycation end products is implicated in the development and progression of diabetic kidney disease. No study has examined whether stimulating advanced glycation clearance via receptor manipulation is reno-protective in diabetes. Podocytes, which are early contributors to diabetic kidney disease and could be a target for reno-protection. To examine the effects of increased podocyte oligosaccharyltransferase-48 on kidney function, glomerular sclerosis, tubulointerstitial fibrosis and proteome (PXD011434), we generated a mouse with increased oligosaccharyltransferase-48kDa subunit abundance in podocytes driven by the podocin promoter. Despite increased urinary clearance of advanced glycation end products, we observed a decline in renal function, significant glomerular damage including glomerulosclerosis, collagen IV deposition, glomerular basement membrane thickening and foot process effacement and tubulointerstitial fibrosis. Analysis of isolated glomeruli identified enrichment in proteins associated with collagen deposition, endoplasmic reticulum stress and oxidative stress. Ultra-resolution microscopy of podocytes revealed denudation of foot processes where there was co-localization of oligosaccharyltransferase-48kDa subunit and advanced glycation end-products. These studies indicate that increased podocyte expression of oligosaccharyltransferase-48kDa subunit results in glomerular endoplasmic reticulum stress and a decline in kidney function.

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