Glomerular podocytes in diabetic renal disease

Podgórski, Paweł; Konieczny, Andrzej; Lis, Łukasz; Witkiewicz, Wojciech; Hruby, Zbigniew

doi:10.17219/acem/104534

Cited by 54 publications

(38 citation statements)

References 38 publications

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“…The most common clinical feature of DN is progressive proteinuria due to impairment of the GFB, and the normal morphology and function of podocytes play an important role in proteinuria formation and maintenance of renal function [ 14 , 15 ]. In many studies, podocytes have been treated with high glucose to cause DN in experimental models [ 16 , 17 ].…”

Section: Discussionmentioning

confidence: 99%

Interleukin 37 (IL-37) Reduces High Glucose-Induced Inflammation, Oxidative Stress, and Apoptosis of Podocytes by Inhibiting the STAT3–Cyclophilin A (CypA) Signaling Pathway

et al. 2020

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Background Diabetic nephropathy (DN), the formation of albuminuria, is one of the most important complications seen in diabetic patients. IL-37, an inhibitor of congenital inflammation and immune response, plays an important role in the occurrence and development of diabetes, but its study in DN has not been previously reported. Material/Methods Podocyte transfection techniques were used to overexpress STAT3 and cyclophilin A (CypA). The expression of IL-37, STAT3, and CypA was detected by RT-qPCR and western blot. Cell survival was detected by CCK-8. The expression of inflammatory factors and molecules related to oxidative stress was detected by ELISA and western blot, and cell apoptosis was detected by flow cytometry and western blot. Results The expression of IL-37 was significantly decreased in high glucose-treated podocytes. IL-37 improved the survival rate of podocytes suffering from high glucose-induced apoptosis. It inhibited the expression of the inflammation-related factors tumor necrosis factor α (TNF-α), IL-1β, IL-6, malondialdehyde (MDA), and lactate dehydrogenase (LDH), and promoted the expression of superoxide dismutase (SOD) in high glucose-treated podocytes. In addition, IL-37 inhibited the expression of the inflammation-related proteins MCP-1, NLRP3, ASC, and caspase-1. IL-37 also inhibited high glucose-induced apoptosis of podocytes by inhibiting the expression of the apoptosis-related proteins Bax and cleaved caspase-3/6/9, and by promoting the expression of Bcl-2. At the same time, we found that the STAT3/CypA signaling pathway was activated after induction by high glucose, while it was inhibited after treatment with IL-37. Overexpression of STAT3 and CypA inhibited the effects of IL-37 on the alleviation of inflammation and oxidative stress and on the reduction of apoptosis of high glucose-treated podocytes. Conclusions IL-37 can significantly reduce podocyte inflammation, oxidative stress, and apoptosis induced by high glucose, and can inhibit the STAT3-CypA signaling pathway. Upregulation of the STAT3-CypA signaling pathway can inhibit the protective effect of IL-37 against podocyte injury induced by high glucose.

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Section: Discussionmentioning

confidence: 99%

Interleukin 37 (IL-37) Reduces High Glucose-Induced Inflammation, Oxidative Stress, and Apoptosis of Podocytes by Inhibiting the STAT3–Cyclophilin A (CypA) Signaling Pathway

et al. 2020

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“…Podocyte injury is also a key feature in the early stage of DKD. Podocytes participate in the formation of the filtration barrier and regulate glomerular filtration, along with the GBM and endothelium [ 12 ]. Therefore, podocyte loss under diabetic conditions results in the damage and hyperpermeability of glomerular endothelial cells, leading to the development of albuminuria [ 13 ].…”

Section: Pathogenesis and Clinical Features Of Dkdmentioning

confidence: 99%

Significance of Metformin Use in Diabetic Kidney Disease

Kawanami

Yuasa

Tanabe

2020

IJMS

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Metformin is a glucose-lowering agent that is used as a first-line therapy for type 2 diabetes (T2D). Based on its various pharmacologic actions, the renoprotective effects of metformin have been extensively studied. A series of experimental studies demonstrated that metformin attenuates diabetic kidney disease (DKD) by suppressing renal inflammation, oxidative stress and fibrosis. In clinical studies, metformin use has been shown to be associated with reduced rates of mortality, cardiovascular disease and progression to end-stage renal disease (ESRD) in T2D patients with chronic kidney disease (CKD). However, metformin should be administered with caution to patients with CKD because it may increase the risk of lactic acidosis. In this review article, we summarize our current understanding of the safety and efficacy of metformin for DKD.

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“…A variety of pathological mechanisms which contribute to diabetic kidney damage have been identified [42]. Injury to the glomerular filtration barrier leads to compromised filtration by the glomerulus which has been linked to the onset of renal fibrosis, potentially due to increased levels of albumin in the urinary filtrate [77]. Hyperglycaemia-induced haemodynamic dysregulation promotes increased production of endogenous vasodilators such as nitric oxide, insulin-like growth factor (IGF) and vascular endothelial growth factor (VEGF) [78].…”

Section: Albuminuria and Diabetic Nephropathymentioning

confidence: 99%

The Potential of Albuminuria as a Biomarker of Diabetic Complications

Raja

Maxwell

Brazil

2020

Cardiovasc Drugs Ther

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Diabetes mellitus is a disease of dysregulated blood glucose homeostasis. The current pandemic of diabetes is a significant driver of patient morbidity and mortality, as well as a major challenge to healthcare systems worldwide. The global increase in the incidence of diabetes has prompted researchers to focus on the different pathogenic processes responsible for type 1 and type 2 diabetes. Similarly, increased morbidity due to diabetic complications has accelerated research to uncover pathological changes causing these secondary complications. Albuminuria, or protein in the urine, is a well-recognised biomarker and risk factor for renal and cardiovascular disease. Albuminuria is a mediator of pathological abnormalities in diabetes-associated conditions such as nephropathy and atherosclerosis. Clinical screening and diagnosis of diabetic nephropathy is chiefly based on the presence of albuminuria. Given the ease in measuring albuminuria, the potential of using albuminuria as a biomarker of cardiovascular diseases is gaining widespread interest. To assess the benefits of albuminuria as a biomarker, it is important to understand the association between albuminuria and cardiovascular disease. This review examines our current understanding of the pathophysiological mechanisms involved in both forms of diabetes, with specific focus on the link between albuminuria and specific vascular complications of diabetes.

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Glomerular podocytes in diabetic renal disease

Cited by 54 publications

References 38 publications

Interleukin 37 (IL-37) Reduces High Glucose-Induced Inflammation, Oxidative Stress, and Apoptosis of Podocytes by Inhibiting the STAT3–Cyclophilin A (CypA) Signaling Pathway

Interleukin 37 (IL-37) Reduces High Glucose-Induced Inflammation, Oxidative Stress, and Apoptosis of Podocytes by Inhibiting the STAT3–Cyclophilin A (CypA) Signaling Pathway

Significance of Metformin Use in Diabetic Kidney Disease

The Potential of Albuminuria as a Biomarker of Diabetic Complications

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