Deficiency of mitochondrial glycerol 3-phosphate dehydrogenase exacerbates podocyte injury and the progression of diabetic kidney disease

Diabetes ◽  
2021 ◽  
pp. db201157
Author(s):  
Hua Qu ◽  
Xiaoli Gong ◽  
Xiufei Liu ◽  
Rui Zhang ◽  
Yuren Wang ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Podocyte Injury ◽  
Diabetic Kidney ◽  
Glycerol 3 Phosphate Dehydrogenase

scholarly journals Deficiency of Mitochondrial Glycerol 3-Phosphate Dehydrogenase Exacerbates Podocyte Injury and the Progression of Diabetic Kidney Disease

2021 ◽  
Author(s):  
Hua Qu ◽  
Xiaoli Gong ◽  
Xiufei Liu ◽  
Rui Zhang ◽  
Yuren Wang ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Mitochondrial Function ◽  
Diabetic Kidney Disease ◽  
Kidney Diseases ◽  
Ros Generation ◽  
Glomerular Injury ◽  
Inner Mitochondrial Membrane ◽  
Podocyte Injury ◽  
Diabetic Kidney ◽  
Glycerol 3 Phosphate Dehydrogenase

Mitochondrial function is essential for bioenergetics, metabolism and signaling and is compromised in diseases such as proteinuric kidney diseases, <a>contributing</a> to the global burden of kidney failure, cardiovascular morbidity and death. The key cell <a>type</a> that prevents proteinuria is the terminally differentiated glomerular podocyte. Here, we <a>characterized</a> the importance of mitochondrial glycerol 3-phosphate dehydrogenase (mGPDH), located on the inner mitochondrial membrane, in regulating podocyte function and glomerular disease. Specifically, podocyte-dominated mGPDH expression was downregulated in the glomeruli of patients and mice with diabetic kidney disease and adriamycin nephropathy. Podocyte-specific depletion of mGPDH in mice exacerbated <a>diabetes-</a> or adriamycin-induced proteinuria, podocyte injury and glomerular pathology. RNA sequencing revealed that mGPDH regulated the RAGE signaling pathway, and inhibition of RAGE or its ligand, S100A10, protected against the impaired mitochondrial bioenergetics and increased ROS generation caused by mGPDH knockdown in cultured podocytes. Moreover, RAGE deletion in podocytes attenuated nephropathy progression in mGPDH-deficient diabetic mice. Rescue of podocyte mGPDH expression in mice with established glomerular injury <a>significantly improved</a> their renal function. In summary, our study proposes that activation of mGPDH induces mitochondrial biogenesis and reinforces mitochondrial function, which may provide a potential therapeutic target for preventing podocyte injury and proteinuria in diabetic kidney disease.

scholarly journals Deficiency of Mitochondrial Glycerol 3-Phosphate Dehydrogenase Exacerbates Podocyte Injury and the Progression of Diabetic Kidney Disease

2021 ◽  
Author(s):  
Hua Qu ◽  
Xiaoli Gong ◽  
Xiufei Liu ◽  
Rui Zhang ◽  
Yuren Wang ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Mitochondrial Function ◽  
Diabetic Kidney Disease ◽  
Kidney Diseases ◽  
Ros Generation ◽  
Glomerular Injury ◽  
Inner Mitochondrial Membrane ◽  
Podocyte Injury ◽  
Diabetic Kidney ◽  
Glycerol 3 Phosphate Dehydrogenase

Mitochondrial function is essential for bioenergetics, metabolism and signaling and is compromised in diseases such as proteinuric kidney diseases, <a>contributing</a> to the global burden of kidney failure, cardiovascular morbidity and death. The key cell <a>type</a> that prevents proteinuria is the terminally differentiated glomerular podocyte. Here, we <a>characterized</a> the importance of mitochondrial glycerol 3-phosphate dehydrogenase (mGPDH), located on the inner mitochondrial membrane, in regulating podocyte function and glomerular disease. Specifically, podocyte-dominated mGPDH expression was downregulated in the glomeruli of patients and mice with diabetic kidney disease and adriamycin nephropathy. Podocyte-specific depletion of mGPDH in mice exacerbated <a>diabetes-</a> or adriamycin-induced proteinuria, podocyte injury and glomerular pathology. RNA sequencing revealed that mGPDH regulated the RAGE signaling pathway, and inhibition of RAGE or its ligand, S100A10, protected against the impaired mitochondrial bioenergetics and increased ROS generation caused by mGPDH knockdown in cultured podocytes. Moreover, RAGE deletion in podocytes attenuated nephropathy progression in mGPDH-deficient diabetic mice. Rescue of podocyte mGPDH expression in mice with established glomerular injury <a>significantly improved</a> their renal function. In summary, our study proposes that activation of mGPDH induces mitochondrial biogenesis and reinforces mitochondrial function, which may provide a potential therapeutic target for preventing podocyte injury and proteinuria in diabetic kidney disease.

IQGAP1 mediates podocyte injury in diabetic kidney disease by regulating nephrin endocytosis

2019 ◽  
Vol 59 ◽  
pp. 13-23 ◽  
Author(s):  
Yipeng Liu ◽  
Hong Su ◽  
Chaoqun Ma ◽  
Dong Ji ◽  
Xiaoli Zheng ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Podocyte Injury ◽  
Diabetic Kidney

scholarly journals Suppressed ER‐associated degradation by intraglomerular cross talk between mesangial cells and podocytes causes podocyte injury in diabetic kidney disease

2020 ◽  
Vol 34 (11) ◽  
pp. 15577-15590
Author(s):  
Daisuke Fujimoto ◽  
Takashige Kuwabara ◽  
Yusuke Hata ◽  
Shuro Umemoto ◽  
Tomoko Kanki ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Cross Talk ◽  
Diabetic Kidney Disease ◽  
Mesangial Cells ◽  
Podocyte Injury ◽  
Diabetic Kidney

scholarly journals The Role of Podocytes and Podocyte-Associated Biomarkers in Diagnosis and Treatment of Diabetic Kidney Disease

2020 ◽  
Vol 4 (4) ◽  
Author(s):  
Igor Kravets ◽  
Sandeep K Mallipattu
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Public Health Problem ◽  
Diabetic Patients ◽  
Tubular Damage ◽  
Preventative Care ◽  
Important Public Health Problem ◽  
Podocyte Injury ◽  
Diabetic Kidney ◽  
Filtration Barrier

Abstract Diabetic kidney disease (DKD) is an important public health problem. Podocyte injury is a central event in the mechanism of DKD development. Podocytes are terminally differentiated, highly specialized glomerular visceral epithelial cells critical for the maintenance of the glomerular filtration barrier. Although potential mechanisms by which diabetic milieu contributes to irreversible loss of podocytes have been described, identification of markers that prognosticate either the development of DKD or the progression to end-stage kidney disease (ESKD) have only recently made it to the forefront. Currently, the most common marker of early DKD is microalbuminuria; however, this marker has significant limitations: not all diabetic patients with microalbuminuria will progress to ESKD and as many as 30% of patients with DKD have normal urine albumin levels. Several novel biomarkers indicating glomerular or tubular damage precede microalbuminuria, suggesting that the latter develops when significant kidney injury has already occurred. Because podocyte injury plays a key role in DKD pathogenesis, identification of markers of early podocyte injury or loss may play an important role in the early diagnosis of DKD. Such biomarkers in the urine include podocyte-released microparticles as well as expression of podocyte-specific markers. Here, we review the mechanisms by which podocyte injury contributes to DKD as well as key markers that have been recently implicated in the development and/or progression of DKD and might serve to identify individuals that require earlier preventative care and treatment in order to slow the progression to ESKD.

scholarly journals Angiotensin II-mediated MYH9 downregulation causes structural and functional podocyte injury in diabetic kidney disease

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jeong Suk Kang ◽  
Seung Joo Lee ◽  
Ji-Hye Lee ◽  
Ji-Hee Kim ◽  
Seung Seob Son ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Podocyte Injury ◽  
Diabetic Kidney

The Role of Cholesterol Homeostasis in Diabetic Kidney Disease

2021 ◽  
Vol 28 ◽  
Author(s):  
Xinyun Chen ◽  
Qinghua Yin ◽  
Liang Ma ◽  
Ping Fu
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Cholesterol Metabolism ◽  
Cholesterol Homeostasis ◽  
Renal Cells ◽  
Kidney Dysfunction ◽  
Podocyte Injury ◽  
Diabetic Kidney ◽  
Considerable Evidence

: Considerable evidence has proved that disturbed cholesterol metabolism played a crucial role in diabetic kidney disease. Besides, massive cholesterol depositions were found in intrinsic renal cells of diabetic kidney disease patients and animal models, causing cytotoxicity, and affecting renal function. Statins could alleviate cholesterol depositions, podocyte injury and microalbuminuria of diabetic kidney disease. In the review, we summarized the process of disturbed cholesterol metabolism and discussed how it induced kidney dysfunction in diabetic kidney disease.

scholarly journals Complement factor B in high glucose–induced podocyte injury and diabetic kidney disease

JCI Insight ◽  
2021 ◽  
Vol 6 (19) ◽  
Author(s):  
Qingmiao Lu ◽  
Qing Hou ◽  
Kai Cao ◽  
Xiaoli Sun ◽  
Yan Liang ◽  
...  
Keyword(s):  
Kidney Disease ◽  
High Glucose ◽  
Diabetic Kidney Disease ◽  
Complement Factor ◽  
Podocyte Injury ◽  
Factor B ◽  
Diabetic Kidney ◽  
Complement Factor B

scholarly journals MP485GASTRIC BYPASS SURGERY IMPROVES ALBUMINURIA AND PODOCYTE INJURY IN EXPERIMENTAL DIABETIC KIDNEY DISEASE

2017 ◽  
Vol 32 (suppl_3) ◽  
pp. iii607-iii607
Author(s):  
Meera Nair ◽  
Aoife Canney ◽  
Jessie Elliott ◽  
Naomi Fearon ◽  
Anna Casselbrant ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Bypass Surgery ◽  
Podocyte Injury ◽  
Diabetic Kidney

scholarly journals MYDGF attenuates podocyte injury and proteinuria by activating Akt/BAD signal pathway in mice with diabetic kidney disease

Diabetologia ◽  
2020 ◽  
Vol 63 (9) ◽  
pp. 1916-1931
Author(s):  
Mingjuan He ◽  
Yixiang Li ◽  
Li Wang ◽  
Bei Guo ◽  
Wen Mei ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Signal Pathway ◽  
Podocyte Injury ◽  
Diabetic Kidney
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