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Pathogenesis diabetic nephropathy

Jin Zhang, Jianhua Liu, Xiaosong Qin
Diabetic nephropathy is the main cause of chronic kidney disease, and represents the most common and serious complication of diabetes. The exact pathogenesis is complex and not elucidated. Several factors and mechanisms contribute to the development and outcome of diabetic nephropathy. An early diagnosis and intervention may slow down disease progression. A variety of biological markers associated with diabetic nephropathy were found in recent years, which was important for predicting the occurrence and development of the disease...
January 2018: Revista da Associação Médica Brasileira
Masaki Kobayashi, Douglas W Zochodne
Diabetic polyneuropathy (DPN) continues to be generally considered as a "microvascular" complication of diabetes mellitus alongside nephropathy and retinopathy. The microvascular hypothesis, however, may be tempered by the concept that diabetes directly targets dorsal root ganglion sensory neurons. This neuron specific concept, supported by accumulating evidence, might account for important features of DPN, such as its early sensory neuron degeneration. Diabetic sensory neurons develop neuronal atrophy alongside a series of mRNA changes related to declines in structural proteins, increases in heat shock protein (HSP), increases in the receptor for advanced glycation endproducts (RAGE), declines in growth factor signaling and other changes...
March 13, 2018: Journal of Diabetes Investigation
Kavisa Ghosh, Indra N
Cadmium (Cd), a potent carcinogen present in almost all foods, poses a major health risk to humans. Major routes of exposure to Cd for humans are occupation, diet, and tobacco use. Cd elicits various deleterious effects on cellular molecules mainly by causing oxidant-antioxidant imbalance. Cd has been implicated in the pathogenesis of many cancers, Itai-itai disease, diabetic nephropathy, hypertension, peripheral artery disease, and myocardial infarction. This study was designed to investigate the effects of Cd intake on erythrocytes and cardiac tissue in male albino Wistar rats...
February 27, 2018: Environmental Toxicology and Pharmacology
C Randall Harrell, Bojana Simovic Markovic, Crissy Fellabaum, Aleksandar Arsenijevic, Valentin Djonov, Vladislav Volarevic
BACKGROUND: Pericytes are multipotent cells present in every vascularized tissue in the body. Despite the fact that they are well-known for more than a century, pericytes are still representing cells with intriguing properties. This is mainly because of their heterogeneity in terms of definition, tissue distribution, origin, phenotype and multi-functional properties. The body of knowledge illustrates importance of pericytes in the regulation of homeostatic and healing processes in the body...
March 9, 2018: Journal of Biomedical Science
Shu-Yan Liu, Jie Chen, Yong-Feng Li
INTRODUCTION: Recent studies suggest that chronic inflammatory responses are important in the development of diabetic nephropathy (DN). Various inflammatory and angiogenesis molecules affect the pathogenesis and progression of DN. Inflammation damages the microcirculation and causes kidney damage. In this study, we studied changes in interleukin-8 (IL-8) and soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) levels in patients with diabetic nephropathy (DN) and investigated the clinical significance of these two inflammatory factors...
February 28, 2018: Journal of Diabetes Investigation
Osamu Ichii, Taro Horino
Mature microRNAs (miRNAs) are single-stranded RNAs with approximately 18-25 bases, and their sequences are highly conserved among animals. miRNAs act as posttranscriptional regulators by binding mRNAs, and their main function involves the degradation of their target mRNAs. Recent studies revealed altered expression of miRNAs in the kidneys during the progression of acute kidney injury (AKI) and chronic kidney disease (CKD) in humans and experimental rodent models by using high-throughput screening techniques including microarray and small RNA sequencing...
January 2018: Journal of Toxicologic Pathology
Megan Stevens, Sebastian Oltean
Vascular endothelial growth factor A (VEGF-A) is a prominent pro-angiogenic and pro-permeability factor in the kidney. Alternative splicing of the terminal exon of VEGF-A through the use of an alternative 3' splice site gives rise to a functionally different family of isoforms, termed VEGF-Axxx b, known to have anti-angiogenic and anti-permeability properties. Dysregulation of the VEGF-Axxx /VEGF-Axxx b isoform balance has recently been reported in several kidney pathologies, including diabetic nephropathy (DN) and Denys-Drash syndrome...
February 15, 2018: Genes
Xiaoyan Bai, Xiao Li, Jianwei Tian, Liting Xu, Jiao Wan, Youhua Liu
There remains a lack of robust mouse models with key features of advanced human diabetic nephropathy (DN). Few options of murine models of DN require mutations to be superimposed to obtain desired phenotypic characteristics. Most genetically modified mice are on the C57BL/6 background; however, they are notorious for resistance to develop DN. To overcome these conundrums, this study reports a novel DN model by challenging with advanced oxidation protein products (AOPPs) in streptozotocin-induced diabetic C57BL/6 mice...
February 17, 2018: Free Radical Biology & Medicine
Quan Zhuang, Ke Cheng, Yingzi Ming
The fractalkine receptor chemokine (C-X3-C motif) receptor 1 (CX3CR1) and its highly selective ligand CX3CL1 mediate chemotaxis and adhesion of immune cells, which are involved in the pathogenesis and progression of numerous inflammatory disorders and malignancies. The CX3CL1/CX3CR1 axis has recently drawn attention as a potential therapeutic target because it is involved in the ontogeny, homeostatic migration, or colonization of renal phagocytes. We performed a Medline/PubMed search to detect recently published studies that explored the relationship between the CX3CL1/CX3CR1 axis and renal diseases and disorders, including diabetic nephropathy, renal allograft rejection, infectious renal diseases, IgA nephropathy, fibrotic kidney disease, lupus nephritis and glomerulonephritis, acute kidney injury and renal carcinoma...
2017: Current Gene Therapy
Xiaodan Wang, Lihui Gao, Hua Lin, Jingling Song, Jinwen Wang, Yumin Yin, Jianghu Zhao, Xiangwei Xu, Zhenkun Li, Ling Li
Diabetic nephropathy (DN) is one of the most severe microangiopathies of diabetes mellitus and is a leading cause of end stage renal disease. Numerous studies suggest that podocyte injury contributes to progressive proteinuria. Podocytes are highly specialized, terminally differentiated cells that are unable to proliferate, autophagy plays a key role in maintaining the structure and function of podocytes. Autophagy impairment is involved in the pathogenesis of podocyte loss, which leads to massive proteinuria in DN...
February 11, 2018: European Journal of Pharmacology
Laila A Rashed, Samah Elattar, Nashwa Eltablawy, Hend Ashour, Lamiaa Mohamed, Yasmin El-Esawy
The aim of this study was to investigate the effect of Melatonin (MT) pretreated mesenchymal stem cells (MSCs) regenerative therapy, as a new therapeutic target in modifying underlying diabetic nephropathy (DN) pathogenesis in a rat model, and its possible effect on autophagy protein Beclin-1. Forty adult male Wistar albino rats divided into four groups: control, DN, MSCs treated (MSCs) and In-vitro Melatonin (5µM for 24 hours) pre-incubated MSCs treated group (MSCs+MT). MSCs treatment significantly improved the renal functions with amelioration of the measured underlying DN pathogenesis and elevation of Beclin-1 protein levels compared to DN group...
February 9, 2018: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
Mina Amanzadeh, Ali Mota, Nosratollah Zarghami, Sima Abedi-Azar, Sina Abroon, Naghmeh Akbarian, Aynaz Mihanfar, Mohammad Rahmati-Yamchi
INTRODUCTION: Diabetic nephropathy is pictured as matrix accumulation and thickening of glomerular basal membrane. Matrix metalloproteinases (MMPs) are major proteases involved in extracellular matrix degradation. Moreover, plasminogen activator inhibitor-1 (PAI-1) primarily regulates plasmin dependent proteolysis. It plays a role in renal fibrosis causing extracellular matrix accumulation through inhibition of plasmin-dependent extracellular matrix degradation. This study investigated PAI-1 serum level and MMP-3 activity and their correlation with glomerular filtration rate in patients with diabetes mellitus...
January 2018: Iranian Journal of Kidney Diseases
Richard Van Krieken, Mandeep Marway, Pavithra Parthasarathy, Neel Mehta, Alistar J Ingram, Bo Gao, Joan C Krepinsky
Sterol regulatory element binding protein (SREBP) is an important potential mediator of kidney fibrosis, and is known to be upregulated in diabetic nephropathy. Here we evaluate the effectiveness of SREBP inhibition as treatment for diabetic nephropathy.Type 1 diabetes was induced in uninephrectomized male CD1 mice with streptozotocin. Mice were treated with the SREBP inhibitor fatostatin for 12 weeks. At endpoint, kidney function and pathology were assessed. Fatostatin inhibited the increase of both isoforms of SREBP (1 and 2) in diabetic kidneys...
February 5, 2018: Endocrinology
Weixia Sun, Jiaxing Yang, Wanning Wang, Jie Hou, Yanli Cheng, Yaowen Fu, Zhonggao Xu, Lu Cai
Zinc is one of the essential trace elements and participates in numerous physiological processes. Abnormalities in zinc homeostasis often result in the pathogenesis of various chronic metabolic disorders, such as diabetes and its complications. Zinc has insulin-mimetic and anti-diabetic effects and deficiency has been shown to aggravate diabetes-induced oxidative stress and tissue injury in diabetic rodent models and human subjects with diabetes. Akt signaling pathway plays a central role in insulin-stimulated glucose metabolism and cell survival...
March 2018: Journal of Trace Elements in Medicine and Biology
Tao Wang, Yan Zhang, Ning Wang, Qiong Liu, ZeKai Wang, Bing Liu, Kai Niu
PURPOSE: Since altered sympathetic nerve activity and insulin resistance are implicated in the pathogenesis of type 2 diabetic nephropathy, we investigated the effect of polymorphic Arg16Gly and Gln27Glu in the β2 adrenoceptor gene and Ala54Thr in the fatty acid binding protein 2 gene on the estimated glomerular filtration rate (eGFR) in Chinese patients with the above disease. METHODS: A total of 552 diabetic subjects recruited from annual health examinations were studied...
February 5, 2018: International Urology and Nephrology
Hongxia Zhang, Yanlan Yang, Yanqin Wang, Baodong Wang, Rongshan Li
Background: Diabetic nephropathy (DN) is a major microvascular complication in diabetes. An increasing body of evidence has shown that DN is related to chronic inflammation, kidney hypertrophy, and fibrosis. While thalidomide has been shown to have anti-inflammatory and antifibrotic effects, the effects of thalidomide on the pathogenesis of DN are unclear. This study was undertaken to explore whether thalidomide has renal-protective effects in diabetic rats. Methods: Male Sprague Dawley rats were injected intraperitoneally with 50 mg/kg streptozotocin to induce diabetes...
2018: Drug Design, Development and Therapy
Daisuke Yamazaki, Hirofumi Hitomi, Akira Nishiyama
Chronic diabetic complications are classified as microvascular or macrovascular and contribute to mortality and loss of quality of life. Hyperglycemia plays a critical role in the pathogenesis of microvascular complications, such as diabetic retinopathy, incipient nephropathy, and neuropathy, while atherosclerosis contributes to the pathogenesis of macrovascular complications. Diabetes mellitus and hypertension are frequently present together. Among many microvascular diabetic complications, hypertension plays a predominant role in the progression of diabetic nephropathy by glomerular hyperfiltration...
January 22, 2018: Hypertension Research: Official Journal of the Japanese Society of Hypertension
Federica Petrillo, Anna Iervolino, Miriam Zacchia, Adelina Simeoni, Cristina Masella, Giovanna Capolongo, Alessandra Perna, Giovambattista Capasso, Francesco Trepiccione
Background: MicroRNAs (miRNAs) are a family of short noncoding RNAs that play important roles in posttranscriptional gene regulation. miRNAs inhibit target gene expression by blocking protein translation or by inducing mRNA degradation and therefore have the potential to modulate physiological and pathological processes. Summary: In the kidney, miRNAs play a role in the organogenesis and in the pathogenesis of several diseases, including renal carcinoma, diabetic nephropathy, cystogenesis, and glomerulopathies...
December 2017: Kidney Diseases
Dominik Chittka, Bernhard Banas, Laura Lennartz, Franz Josef Putz, Kathrin Eidenschink, Sebastian Beck, Thomas Stempfl, Christoph Moehle, Simone Reichelt-Wurm, Miriam C Banas
Background: Although diabetic nephropathy (DN) is the most common cause for end-stage renal disease in western societies, its pathogenesis still remains largely unclear. A different gene pattern of diabetic and healthy kidney cells is one of the probable explanations. Numerous signalling pathways have emerged as important pathophysiological mechanisms for diabetes-induced renal injury. Methods: Glomerular cells, as podocytes or mesangial cells, are predominantly involved in the development of diabetic renal lesions...
January 11, 2018: Nephrology, Dialysis, Transplantation
Xiao-Bing Wang, Hong Zhu, Wei Song, Jian-Hua Su
BACKGROUND Gremlin has been reported to be up-regulated in glomerular mesangial cells in diabetic nephropathy (DN). However, the regulation of gremlin in podocytes is still rarely reported. This study aimed to investigate the underlying mechanisms by which gremlin mediates the pathogenesis of DN via transforming growth factor-β (TGF-β) signaling pathways. MATERIAL AND METHODS Lentiviral and RNAi transfection were performed to increase and decrease gremlin expression in high-glucose conditions. Expression at the mRNA and protein level was detected by RT-qPCR and Western blotting...
January 9, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
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