Mitochondrial dysfunction as a pathological mediator in diabetic kidney disease

2021 ◽  
Author(s):  
◽  
Nicole Flemming
Keyword(s):  
Kidney Disease ◽  
Mitochondrial Dysfunction ◽  
Diabetic Kidney Disease ◽  
Diabetic Kidney

scholarly journals Glomerular Endothelial Mitochondrial Dysfunction Is Essential and Characteristic of Diabetic Kidney Disease Susceptibility

Diabetes ◽  
2016 ◽  
Vol 66 (3) ◽  
pp. 763-778 ◽  
Author(s):  
Haiying Qi ◽  
Gabriella Casalena ◽  
Shaolin Shi ◽  
Liping Yu ◽  
Kerstin Ebefors ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Mitochondrial Dysfunction ◽  
Diabetic Kidney Disease ◽  
Disease Susceptibility ◽  
Diabetic Kidney

scholarly journals Mitochondrial Regulation of Diabetic Kidney Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Daniel L. Galvan ◽  
Koki Mise ◽  
Farhad R. Danesh
Keyword(s):  
Kidney Disease ◽  
Mitochondrial Dysfunction ◽  
Diabetic Kidney Disease ◽  
Mitochondrial Morphology ◽  
Mitochondria Dysfunction ◽  
Diabetic Kidney ◽  
Mitochondrial Regulation ◽  
Mitochondrial Remodeling ◽  
Remarkable Progress

The role and nature of mitochondrial dysfunction in diabetic kidney disease (DKD) has been extensively studied. Yet, the molecular drivers of mitochondrial remodeling in DKD are poorly understood. Diabetic kidney cells exhibit a cascade of mitochondrial dysfunction ranging from changes in mitochondrial morphology to significant alterations in mitochondrial biogenesis, biosynthetic, bioenergetics and production of reactive oxygen species (ROS). How these changes individually or in aggregate contribute to progression of DKD remain to be fully elucidated. Nevertheless, because of the remarkable progress in our basic understanding of the role of mitochondrial biology and its dysfunction in DKD, there is great excitement on future targeted therapies based on improving mitochondrial function in DKD. This review will highlight the latest advances in understanding the nature of mitochondria dysfunction and its role in progression of DKD, and the development of mitochondrial targets that could be potentially used to prevent its progression.

scholarly journals Mitochondrial DNA: A New Predictor of Diabetic Kidney Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Yajing Huang ◽  
Jingwei Chi ◽  
Fanxiang Wei ◽  
Yue Zhou ◽  
Yihai Cao ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Mitochondrial Dysfunction ◽  
Large Scale ◽  
Diabetic Kidney Disease ◽  
Endothelial Damage ◽  
Inflammatory Factors ◽  
Mtdna Copy Number ◽  
Diabetic Kidney ◽  
Patients With Diabetes ◽  
Stage Renal Disease

Diabetic kidney disease (DKD) is a common cause of end-stage renal disease, and diagnosis and treatment in time can help delay its progress. At present, there are more and more studies on the pathogenesis of DKD; mitochondrial dysfunction plays an important role in DKD. The occurrence and development of DKD is closely related to epigenetic changes and the interaction between mtDNA, ROS, inflammatory factors, and endothelial damage, which continuously aggravates kidney. The change of mtDNA is both the cause of DKD and the result of DKD. It is of great significance to incorporate the change of mtDNA into the monitoring of patients with diabetes. Existing evidence indicates that changes in mtDNA copy number in blood and urine reflect mitochondrial dysfunction and the severity of DKD. However, large-scale, long-term follow-up clinical trials are still needed to determine the threshold range. By the time, mitochondrial-targeted antioxidants will become a new method for the treatment of DKD and other diabetic complications; mtDNA also can be a therapeutic target for them.

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.

Mitochondrial dysfunction in diabetic kidney disease

2019 ◽  
Vol 496 ◽  
pp. 108-116 ◽  
Author(s):  
Pascal Zhongping Wei ◽  
Cheuk Chun Szeto
Keyword(s):  
Kidney Disease ◽  
Mitochondrial Dysfunction ◽  
Diabetic Kidney Disease ◽  
Diabetic Kidney

Mitochondrial dysfunction in diabetic kidney disease

2018 ◽  
Vol 14 (5) ◽  
pp. 291-312 ◽  
Author(s):  
Josephine M. Forbes ◽  
David R. Thorburn
Keyword(s):  
Kidney Disease ◽  
Mitochondrial Dysfunction ◽  
Diabetic Kidney Disease ◽  
Diabetic Kidney

Mitochondrial Dysfunction and Signaling in Diabetic Kidney Disease: Oxidative Stress and Beyond

2018 ◽  
Vol 38 (2) ◽  
pp. 101-110 ◽  
Author(s):  
Nicole Bernadette Flemming ◽  
Linda Alba Gallo ◽  
Josephine Maree Forbes
Keyword(s):  
Oxidative Stress ◽  
Kidney Disease ◽  
Mitochondrial Dysfunction ◽  
Diabetic Kidney Disease ◽  
Diabetic Kidney
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