scholarly journals Caspase-3 Promotes Diabetic Kidney Disease Through Gasdermin E-Mediated Progression to Secondary Necrosis During Apoptosis

2020 ◽  
Vol Volume 13 ◽  
pp. 313-323
Author(s):  
Si Wen ◽  
Zhao-Hua Wang ◽  
Cong-Xiao Zhang ◽  
Ying Yang ◽  
Qiu-Ling Fan
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Caspase 3 ◽  
Diabetic Kidney ◽  
Secondary Necrosis

scholarly journals The Role of TLR4 on PGC-1α-Mediated Oxidative Stress in Tubular Cell in Diabetic Kidney Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Shuguang Yuan ◽  
Xuemei Liu ◽  
Xuejing Zhu ◽  
Zhong Qu ◽  
Zailiang Gong ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Cytochrome C ◽  
Oxidative Damage ◽  
Mitochondrial Dysfunction ◽  
Diabetic Kidney Disease ◽  
Caspase 3 ◽  
Tubular Cell ◽  
Renal Tubules ◽  
Diabetic Mice ◽  
Diabetic Kidney

The role and precise mechanism of TLR4 in mitochondria-related oxidative damage and apoptosis of renal tubules in diabetic kidney disease (DKD) remain unclear. We examined the expression of TLR4 in renal biopsy tissues. Db/db diabetic mice and HK-2 cells cultured under high glucose (HG) were used as in vivo and vitro models. Real-time RT-PCR, Western blot, and immunohistochemistry were performed to examine the mRNA and protein levels of TLR4, NF-κΒ, PGC-1α, cytochrome C, and cleaved caspase-3. ATP level, activity of electron transport chain complex III, and antioxidant enzymes were investigated for mitochondrial function. Electron microscopy (EM) and MitoTracker Red CMXRos were used for mitochondrial morphology alteration. DHE staining and TUNEL assay were detected for ROS accumulation and apoptosis. PGC-1α plasmids were used for the overexpression of PGC-1α in HK-2. TAK242 and parthenolide were used as TLR4 and NF-κB blockers, respectively. Results showed that TLR4 was extensively expressed in the renal tubules of DKD patients and db/db diabetic mice, which was positively related to the tubular interstitial damage score and urinary β-NAG levels. In diabetic mice, inhibition of TLR4 could reverse the decreased expression of PGC-1α, increased expression of cytochrome C and cleaved caspase-3, mitochondrial dysfunction and deformation, increased accumulation of ROS, and activation of tubular cell apoptosis. In vitro, inhibition of TLR4 or NF-κB showed consistent results. PGC-1α overexpression could reverse the mitochondrial dysfunction, increased cleaved caspase-3, and apoptosis in HK-2 cells treated with HG. Data indicated that the TLR4/NF-κB signaling pathway might be the upstream pathway of PGC-1α and promote the tubular damage of DKD by modulating the mitochondria-related oxidative damage and apoptosis.

scholarly journals Tongxinluo preserves the renal function in diabetic kidney disease via protecting the HK-2 cells from the patterns of programmed cell death

2021 ◽  
Vol 16 (2) ◽  
pp. 52-64
Author(s):  
Shuang Shen ◽  
Yunlong Hou ◽  
Yiling Wu
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Caspase 3 ◽  
Excretion Rate ◽  
Underlying Mechanism ◽  
Diabetic Kidney ◽  
Caspase 1 ◽  
Urine Albumin ◽  
Proximal Tubular ◽  
Cells Cultured

This study was explored the renoprotective effect of Tongxinluo (a Traditional Chinese Medicine) on diabetic kidney disease and its underlying mechanism. The results revealed significant (p<0.05) up-regulation of the expression of Bcl-2 and down-regulation of NF-κB p-p65, ASC, NLRP3, caspase-1, cleaved GSDMD, IL-1β, caspase-3, Bax and the ratio of Bcl-2 and Bax in immortalized proximal tubular HK-2 cells cultured by hyperglycemia combined with hyperlipidemia. In db/db mice, Tongxinluo treatment substantially decreased the 24 hours albuminuria excretion rate and the urine albumin-creatinine ratios and renal morphologic abnormalities. Similarly, the levels of NF-κB p-p65, NLRP3, caspase-1, cleaved GSDMD, IL-1β, caspase-3, and the ratio of Bcl-2 and Bax were down-regulated by Tongxinluo treatment in the kidney samples of db/db mice (p<0.05). Taken together, according to the anti-pyroptosis and anti-apoptosis effect of Tongxinluo, it shows the potential to be effective for the treatment of diabetic kidney disease.

Systems Medicine Derived Biomarkers to Assess How Canagliflozin Delays Progression of Diabetic Kidney Disease

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1126-P
Author(s):  
HIDDO LAMBERS. HEERSPINK ◽  
PAUL PERCO ◽  
JOHANNES LEIERER ◽  
MICHAEL K. HANSEN ◽  
ANDREAS HEINZEL ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Systems Medicine ◽  
Diabetic Kidney

Factors Related to the High Prevalence of Diabetic Kidney Disease in Ecuador-Update for Health Policy Makers

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 526-P
Author(s):  
MARIANA E. GUADALUPE ◽  
GRACIELA B. ALVAREZ CONDO ◽  
FANNY E. VERA LORENTI ◽  
BETTY J. PAZMIÑO GOMEZ ◽  
EDGAR I. RODAS NEIRA ◽  
...  
Keyword(s):  
Health Policy ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Policy Makers ◽  
Diabetic Kidney ◽  
High Prevalence

Albuminuria Is More Closely Associated with Vascular Endothelial Function than eGFR in Type 2 Diabetes with Diabetic Kidney Disease

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 443-P
Author(s):  
YOSHINORI KAKUTANI ◽  
MASANORI EMOTO ◽  
YUKO YAMAZAKI ◽  
KOKA MOTOYAMA ◽  
TOMOAKI MORIOKA ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Kidney Disease ◽  
Endothelial Function ◽  
Diabetic Kidney Disease ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function ◽  
Diabetic Kidney

539-P: The Trend of Diabetic Kidney Disease with Low eGFR and Absence of Albuminuria in Type 2 Diabetic Patients in Japan from 1996-2015

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 539-P
Author(s):  
YOSHINORI KAKUTANI ◽  
MASANORI EMOTO ◽  
KATSUHITO MORI ◽  
YUKO YAMAZAKI ◽  
AKINOBU OCHI ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Diabetic Kidney ◽  
Type 2 Diabetic

236-OR: Effects of Dapagliflozin on Progression of Diabetic Kidney Disease: Analysis from DECLARE-TIMI 58 Trial

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 236-OR
Author(s):  
OFRI MOSENZON ◽  
STEPHEN D. WIVIOTT ◽  
THOMAS A. ZELNIKER ◽  
HIDDO L. HEERSPINK ◽  
JAMIE P. DWYER ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Diabetic Kidney ◽  
Disease Analysis
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