scholarly journals GPR43 activation-mediated lipotoxicity contributes to podocyte injury in diabetic nephropathy by modulating the ERK/EGR1 pathway

2022 ◽  
Vol 18 (1) ◽  
pp. 96-111
Author(s):  
Jian Lu ◽  
Pei Pei Chen ◽  
Jia Xiu Zhang ◽  
Xue Qi Li ◽  
Gui Hua Wang ◽  
...  
Author(s):  
Guibao Ke ◽  
Xueqin Chen ◽  
Ruyi Liao ◽  
Lixia Xu ◽  
Li Zhang ◽  
...  

Gene ◽  
2020 ◽  
Vol 747 ◽  
pp. 144661 ◽  
Author(s):  
Tao Yao ◽  
Dongqing Zha ◽  
Chun Hu ◽  
Xiaoyan Wu

2020 ◽  
Vol 11 (4) ◽  
pp. 3706-3718 ◽  
Author(s):  
Min-you Qi ◽  
Xu-tao Wang ◽  
Hui-lin Xu ◽  
Zhang-liang Yang ◽  
Yin Cheng ◽  
...  

Ferulic acid protects against diabetic nephropathy in STZ-induced rats by attenuating oxidative stress, inflammation, fibrosis and podocyte injury.


2015 ◽  
Vol 761 ◽  
pp. 116-124 ◽  
Author(s):  
Eunsoo Jung ◽  
Junghyun Kim ◽  
Sung Ho Kim ◽  
Sanghwa Kim ◽  
Myung-Haing Cho

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Junghyun Kim ◽  
Eunjin Shon ◽  
Chan-Sik Kim ◽  
Jin Sook Kim

Hyperglycemia promotes oxidative stress and hence generation of reactive oxygen species (ROS), which is known to play a crucial role in the pathogenesis of diabetic nephropathy. Metformin, an oral hypoglycemic drug, possesses antioxidant effects. The aim of this paper is to investigate the protective effects of metformin on the injury of renal podocytes in spontaneously diabetic Torii (SDT) rats, a new model for nonobese type 2 diabetes. Metformin (350 mg/kg/day) was given to SDT rats for 17 weeks. Blood glucose, glycated haemoglobin (HbA1c), and albuminuria were examined. Kidney histopathology, renal 8-hydroxydeoxyguanosine (8-OHdG) levels and apoptosis were examined. In 43-week-old SDT rats, severe hyperglycemia was developed, and albuminuria was markedly increased. Diabetes induced significant alterations in renal glomerular structure. In addition, urinary and renal 8-OHdG levels were highly increased, and podocyte loss was shown through application of the TUNEL and synaptopodin staining. However, treatment of SDT rats with metformin restored all these renal changes. Our data suggested that diabetes-induced podocyte loss in diabetic nephropathy could be suppressed by the antidiabetes drug, metformin, through the repression of oxidative injury.


2017 ◽  
Vol 65 (8) ◽  
pp. 1093-1101 ◽  
Author(s):  
Madhura Bose ◽  
Sadia Almas ◽  
Sharma Prabhakar

Nephropathy is a major microvascular complication of diabetes mellitus and often leads to terminal renal failure in addition to contributing significantly to cardiovascular morbidity and mortality. Despites continuous advances, the pathogenesis of diabetic nephropathy remains poorly understood. Recent studies have underscored the significance of structural and functional changes in podocytes in the development and progression of diabetic nephropathy. The role of podocytes in health and diabetic nephropathy and abnormalities including podocyte hypertrophy, effacement, and apoptosis, and a detailed discussion on the role played by the Wnt-β-catenin signaling pathway in podocyte injury and dysfunction are the focus of this review. In addition, the role played by Wnt signaling in mediating the effects of known therapeutic strategies for diabetic nephropathy is also discussed.


2014 ◽  
Vol 222 (1) ◽  
pp. 43-51 ◽  
Author(s):  
Tetsuhiro Kakimoto ◽  
Kinya Okada ◽  
Yoshihiro Hirohashi ◽  
Raissa Relator ◽  
Mizue Kawai ◽  
...  

Diabetic nephropathy is a major complication in diabetes and a leading cause of end-stage renal failure. Glomerular podocytes are functionally and structurally injured early in diabetic nephropathy. A non-obese type 2 diabetes model, the spontaneously diabetic Torii (SDT) rat, is of increasing preclinical interest because of its pathophysiological similarities to human type 2 diabetic complications including diabetic nephropathy. However, podocyte injury in SDT rat glomeruli and the effect of angiotensin II receptor blocker treatment in the early stage have not been reported in detail. Therefore, we have evaluated early stages of glomerular podocyte damage and the beneficial effect of early treatment with losartan in SDT rats using desmin as a sensitive podocyte injury marker. Moreover, we have developed an automated, computational glomerulus recognition method and illustrated its specific application for quantitatively studying glomerular desmin immunoreactivity. This state-of-the-art method enabled automatic recognition and quantification of glomerular desmin-positive areas, eliminating the need to laboriously trace glomerulus borders by hand. The image analysis method not only enabled assessment of a large number of glomeruli, but also clearly demonstrated that glomerular injury was more severe in the juxtamedullary region than in the superficial cortex region. This applied not only in SDT rat diabetic nephropathy but also in puromycin aminonucleoside-induced nephropathy, which was also studied. The proposed glomerulus image analysis method combined with desmin immunohistochemistry should facilitate evaluations in preclinical drug efficacy studies as well as elucidation of the pathophysiology of diabetic nephropathy.


2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Kaichiro Sawada ◽  
Masao Toyoda ◽  
Noriko Kaneyama ◽  
Sawako Shiraiwa ◽  
Hitomi Moriya ◽  
...  

Background. Podocyte injury plays an important role in the onset and progression of diabetic nephropathy (DN). Downregulation ofα3β1-integrin expression in podocytes is thought to be associated with podocyte detachment from the glomerular basement membrane, although the mechanisms remain obscure. To determine the mechanism of podocyte detachment, we analyzed the expression levels ofα3β1-integrin in podocytes in early and advanced stages of DN.Methods. Surgical specimens from DN patients were examined byin situhybridization, and the expression levels ofα3- andβ1-integrin subunits in glomeruli of early (n=6) and advanced (n=8) stages were compared with those of normal glomeruli (n=5). Heat-sensitive mouse podocytes (HSMP) were cultured with TGF-β1 to reproduce the microenvironment of glomeruli of DN, and the expression levels of integrin subunits and the properties of migration and attachment were examined.Results. Podocytes of early-stage DN showed upregulation ofα3- andβ1-integrin expression while those of advanced stage showed downregulation. Real-time PCR indicated a tendency for upregulation ofα3- andβ1-integrin in HSMP cultured with TGF-β1. TGF-β1-stimulated HSMP also showed enhancedin vitromigration and attachment on collagen substrate.Conclusions. The results suggested that podocyte detachment during early stage of DN is mediated through upregulation ofα3β1-integrin.


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