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Pathogenesis diabetic nephropathy

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https://www.readbyqxmd.com/read/28726774/interleukin-22-ameliorated-renal-injury-and-fibrosis-in-diabetic-nephropathy-through-inhibition-of-nlrp3-inflammasome-activation
#1
Shaofei Wang, Yubin Li, Jiajun Fan, Xuyao Zhang, Jingyun Luan, Qi Bian, Tao Ding, Yichen Wang, Ziyu Wang, Ping Song, Daxiang Cui, Xiaobin Mei, Dianwen Ju
Diabetic nephropathy (DN) is one of the most lethal complications of diabetes mellitus with metabolic disorders and chronic inflammation. Although the cytokine IL-22 was initially implicated in the pathogenesis of chronic inflammatory diseases, recent studies suggested that IL-22 could suppress inflammatory responses and alleviate tissue injury. Herein, we examined the role of IL-22 in DN. We found that serum levels of IL-22 were significantly downregulated in both patients and mice with DN. The expression of IL-22 was further decreased with the progression of DN, whereas IL-22 gene therapy significantly ameliorated renal injury and mesangial matrix expansion in mice with established nephropathy...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28721497/normoalbuminuric-diabetic-kidney-disease
#2
REVIEW
Chao Chen, Chang Wang, Chun Hu, Yachun Han, Li Zhao, Xuejing Zhu, Li Xiao, Lin Sun
Diabetic kidney disease (DKD) is one of the primary causes of end-stage renal disease (ESRD). Early diagnosis is very important in preventing the development of DKD. Urinary albumin excretion rate (UAER) and glomerular filtration rate (GFR) are widely accepted as criteria for the diagnosis and clinical grading of DKD, and microalbuminuria has been recommended as the first clinical sign of DKD. The natural history of DKD has been divided into three stages: normoalbuminuria, microalbuminuria, and macroalbuminuria...
July 18, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/28708885/pioglitazone-ameliorates-glomerular-nlrp3-inflammasome-activation-in-apolipoprotein-e-knockout-mice-with-diabetes-mellitus
#3
Yao Wang, Bo Yu, Li Wang, Ming Yang, Zhiyin Xia, Wei Wei, Fengyu Zhang, Xiaochen Yuan
OBJECTIVE: The NLRP3 inflammasome plays an important role in the pathogenesis of inflammation in diabetic nephropathy (DN). Pioglitazone (PIO) has been found to exert an anti-inflammatory effect in patients with diabetes mellitus, but it is still unclear whether PIO exhibits a similar effect in DN. We aimed to explore the effect and underlying mechanism of PIO on DN, as well as investigate if NLRP3 is a pharmacologic target of PIO. METHODS: We divided 48 apolipoprotein E (apoE) (-/-) mice into 4 groups: apoE (-/-), apoE (-/-) with PIO, diabetic apoE (-/-), and diabetic apoE (-/-) with PIO...
2017: PloS One
https://www.readbyqxmd.com/read/28704754/metabolomics-study-of-cadmium-induced-diabetic-nephropathy-and-protective-effect-of-caffeic-acid-phenethyl-ester-using-uplc-q-tof-ms-combined-with-pattern-recognition
#4
Pin Gong, Xiangna Chang, Xuefeng Chen, Xiaohuan Bai, He Wen, Sihui Pi, Wenjuan Yang, Lan Wang, Fuxin Chen
Diabetic nephropathy (DN) is the most severe complication of diabetes and multiple factors are involved in the pathogenesis of DN. Among them, cadmium (Cd) acts as a risk factor inducing the occurrence of DN. The present study focused on investigating the protective role of caffeic acid phenethyl ester (CAPE), an active component of propolis from honeybee hives, against Cd-induced DN in mice based on ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS)and pattern recognition...
June 28, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28700904/inhibition-of-high-glucose-induced-inflammation-and-fibrosis-by-a-novel-curcumin-derivative-prevents-renal-and-heart-injury-in-diabetic-mice
#5
Hongjin Chen, Xi Yang, Kongqin Lu, Chun Lu, Yunjie Zhao, Suqing Zheng, Jieli Li, Zhangjian Huang, Yi Huang, Yali Zhang, Guang Liang
Hyperglycemia-induced inflammation and fibrosis have important roles in the pathogenesis of diabetic nephropathy and cardiomyopathy. With inflammatory cytokines and signaling pathways as important mediators, targeting inflammation may be an effective approach to new avenue for treating diabetic complications. J17, a molecule with structural similarities to curcumin, exhibited good anti-inflammatory activities by inhibiting LPS-induced inflammatory response in macrophages. However, its ability to alleviate hyperglycemia-induced injury via its anti-inflammatory actions remained unclear...
July 9, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28700893/coronary-microvascular-disease-as-an-early-culprit-in-the-pathophysiology-of-diabetes-and-metabolic-syndrome
#6
REVIEW
Hicham Labazi, Aaron J Trask
Metabolic syndrome (MetS) is a group of cardio-metabolic risk factors that includes obesity, insulin resistance, hypertension, and dyslipidemia; these are also a combination of independent coronary artery disease (CAD) risk factors. Alarmingly, the prevalence of MetS risk factors are increasing and a leading cause for mortality. In the vasculature, complications from MetS and type 2 diabetes (T2D) can be divided into microvascular (retinopathy and nephropathy) and macrovascular (cardiovascular diseases and erectile dysfunction)...
July 9, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28698746/study-of-visfatin-level-in-type-1-diabetic-children-and-adolescents
#7
Mona H El Samahi, Nagwa Abdallah Ismail, Randa M Matter, Abeer Selim, Alshaymaa Ahmed Ibrahim, Walaa Nabih
BACKGROUND: Visfatin is an intracellular enzyme, known as nicotinamide phosphoribosyltransferase (Nampt) and pre-B-cell colony-enhancing factor (PBEF-1). It has insulin-mimetic effects and lowers plasma glucose levels. AIM: The aim of the work was to assess serum concentration of Visfatin in type 1 diabetic children and adolescents and study its relationships with duration of diabetes, body mass index (BMI), glycemic control, insulin dosage, lipid profile and microvascular complications...
June 15, 2017: Open Access Macedonian Journal of Medical Sciences
https://www.readbyqxmd.com/read/28659030/tongxinluo-inhibits-renal-fibrosis-in-diabetic-nephropathy-involvement-of-the-suppression-of-intercellular-transfer-of-tgf-formula-see-text-1-containing-exosomes-from-gecs-to-gmcs
#8
Xiao-Ming Wu, Yan-Bin Gao, Li-Ping Xu, Da-Wei Zou, Zhi-Yao Zhu, Xiao-Lei Wang, Wei-Jie Yao, Liang-Tao Luo, Yu Tong, Nian-Xiu Tian, Zhe-Ji Han, Wan-Yu Dang
Glomerular mesangial cells (GMCs) activation is implicated in the pathogenesis of diabetic nephropathy (DN). Our previous study revealed that high glucose (HG)-treated glomerular endothelial cells (GECs) produce an increased number of TGF-β1-containing exosomes to activate GMCs through the TGF-β1/Smad3 signaling pathway. We also identified that Tongxinluo (TXL), a traditional Chinese medicine, has beneficial effects on the treatment of DN in DN patients and type 2 diabetic mice. However, it remained elusive whether TXL could ameliorate renal structure and function through suppression of intercellular transfer of TGF-β1-containing exosomes from GECs to GMCs...
June 28, 2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/28658824/prevalence-of-non-alcoholic-fatty-liver-disease-and-its-association-with-diabetic-nephropathy-in-patients-with-type-2-diabetes-mellitus
#9
Zahra Heidari, Atiyeh Gharebaghi
INTRODUCTION: Non Alcoholic Fatty Liver Disease (NAFLD) and Type 2 Diabetes Mellitus (T2DM) are two common problems affecting global health as these two conditions can influence each other. There is very little information about the possible association between NAFLD and diabetic microvascular complications such as diabetic nephropathy. AIM: The aim of this study was to evaluate the prevalence of NAFLD in patients with T2DM and to investigate the association between NAFLD and diabetic nephropathy in these patients...
May 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28658762/role-of-immunofluorescence-in-adult-onset-nephrotic-syndrome-a-study-in-a-tertiary-care-centre-of-western-india
#10
Sharada Rane, Prerana Mutyal, Nicholas Dcunha, Mayur Parkhi, Meenal Jadhav
INTRODUCTION: Study of renal Immunofluorescence (IF) is an ancillary but essential technique in evaluation of renal biopsies in glomerulopathies and also it enlightens on the pathogenesis of nephrotic syndrome. AIM: To determine the role of IF in evaluating definite subtyping and diagnosis of adult onset nephrotic syndrome and attempting clinicopathological correlation. MATERIALS AND METHODS: A total of 52 patients of adult onset nephrotic syndrome were evaluated clinically and with pertinent investigations; and subjected to USG guided percutaneous renal biopsy which was processed and stained for light microscopy and for immunofluorescence by direct method (DIF) using antibodies against IgG, IgM, IgA and C3...
May 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28656084/synergism-effects-of-pioglitazone-and-urtica-dioica-extract-in-streptozotocin-induced-nephropathy-via-attenuation-of-oxidative-stress
#11
Mohammad Shokrzadeh, Sara Sadat-Hosseini, Marjan Fallah, Fatemeh Shaki
OBJECTIVES: Hyperglycemia promotes oxidative stress that plays a crucial role in the pathogenesis of Diabetic nephropathy (DN). In this study, we investigated the synergism effects of hydroalcoholic extract of Urtica dioica and pioglitazone (PIO) on the prevention of DN in streptozotocin induced-diabetic mice. MATERIALS AND METHODS: Forty-two mice were divided into six groups as follows: non-diabetic control group, DMSO group (as solvent), diabetic group and four treatment groups which received U...
May 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28648975/effect-of-extract-of-pueraria-tuberosa-on-expression-of-hypoxia-inducible-factor-1%C3%AE-and-vascular-endothelial-growth-factor-in-kidney-of-diabetic-rats
#12
Rashmi Shukla, Nidhi Pandey, Somanshu Banerjee, Yamini B Tripathi
BACKGROUNDS: Kidney hypoxia represents a unifying mechanism in the pathogenesis of diabetic nephropathy. Hypoxia-induced factor (HIF)-1α mediates the metabolic responses of renal hypoxia by modulating the expression of VEGF. In the present study, we investigated the effect of Pueraria tuberosa extract (PTY-2r) on the expression of HIF-1α, VEGF and nephrin in streptozotocin (STZ) induced diabetic nephropathy (DN). METHODS: The model of diabetic nephropathy (DN) was produced by intraperitoneal injection of 55mg/kg of STZ and maintained for 60days...
June 22, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28646406/podocytes-and-the-quest-for-precision-medicines-for-kidney-diseases
#13
REVIEW
Peter Mundel
In this review, I describe a 30-year journey in the quest for precision medicines for patients with kidney diseases. In 1987, when I started my reseach career, most scientists studying glomerular disease biology were focused on mesangial cells. The crucial role of the podocyte in many kidney diseases characterized by proteinuria, including focal segmental glomerulosclerosis (FSGS) and diabetic nephropathy, had not yet been recognized. We were not aware of genetic causes or drivers of kidney diseases nor of molecular markers and cell culture systems for mechanistic studies of podocyte biology...
June 23, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28643424/mdm2-is-implicated-in-high-glucose-induced-podocyte-mitotic-catastrophe-via-notch1-signalling
#14
Hui Tang, Chun-Tao Lei, Chen Ye, Pan Gao, Cheng Wan, Shan Chen, Fang-Fang He, Yu-Mei Wang, Hua Su, Chun Zhang
Podocyte injury and depletion are essential events involved in the pathogenesis of diabetic nephropathy (DN). As a terminally differentiated cell, podocyte is restricted in 'post-mitosis' state and unable to regenerate. Re-entering mitotic phase will cause podocyte disastrous death which is defined as mitotic catastrophe (MC). Murine double minute 2 (MDM2), a cell cycle regulator, is widely expressed in renal resident cells including podocytes. Here, we explore whether MDM2 is involved in podocyte MC during hyperglycaemia...
June 23, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28637012/infiltrating-macrophages-in-diabetic-nephropathy-promote-podocytes-apoptosis-via-tnf-%C3%AE-ros-p38mapk-pathway
#15
Yinfeng Guo, Zhixia Song, Min Zhou, Ying Yang, Yu Zhao, Bicheng Liu, Xiaoliang Zhang
Macrophage infiltration has been linked to the pathogenesis of diabetic nephropathy (DN). However, how infiltrating macrophages affect the progression of DN is unknown. Although infiltrating macrophages produce pro-inflammatory mediators and induce apoptosis in a variety of target cells, there are no studies in podocytes. Therefore, we tested the contribution of macrophages to podocytes apoptosis in DN. in vivo experiments showed that apoptosis in podocytes was increased in streptozocin (STZ)-induced diabetic rats compared with control rats and that this apoptosis was accompanied by increased macrophages infiltration in the kidney...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28626027/selective-activation-of-epidermal-growth-factor-receptor-in-renal-proximal-tubule-induces-tubulointerstitial-fibrosis
#16
Jessica M Overstreet, Yinqiu Wang, Xin Wang, Aolei Niu, Leslie S Gewin, Bing Yao, Raymond C Harris, Ming-Zhi Zhang
Epidermal growth factor receptor (EGFR) has been implicated in the pathogenesis of diabetic nephropathy and renal fibrosis; however, the causative role of sustained EGFR activation is unclear. Here, we generated a novel kidney fibrotic mouse model of persistent EGFR activation by selectively expressing the EGFR ligand, human heparin-binding EGF-like growth factor (HB-EGF), in renal proximal tubule epithelium. Human HB-EGF expression increased tyrosine kinase phosphorylation of EGFR and the subsequent activation of downstream signaling pathways, including ERK and AKT, as well as the profibrotic TGF-β1/SMAD pathway...
June 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28600173/autophagy-upregulation-ameliorates-cell-injury-in-sequestosome-1-knockout-podocytes-in%C3%A2-vitro
#17
Zhaoping Li, Yuan Yuan, Yan Meng, Ying Rong, Hao Bai, Liyong Chen
Autophagy is a catabolic process to maintain intracellular homeostasis that degrades damaged proteins and organelles in mammalian cells. Podocytes are crucial for maintaining the normal function of the glomerular filtration barrier. In the present study, we aimed to investigate the high glucose-induced cell injury in human podocytes and the protective role of autophagy in this process. Here we show that the autophagy activity was decreased under the high glucose conditions and 72 h of high glucose exposure inhibited the cell viablity and aggravated cell injury...
August 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28596971/soluble-urokinase-receptor-and-the-kidney-response-in-diabetes-mellitus
#18
REVIEW
Ranadheer R Dande, Vasil Peev, Mehmet M Altintas, Jochen Reiser
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) worldwide. DN typically manifests by glomerular hyperfiltration and microalbuminuria; then, the disease progresses to impaired glomerular filtration rate, which leads to ESRD. Treatment options for DN include the strict control of blood glucose levels and pressure (e.g., intraglomerular hypertension). However, the search for novel therapeutic strategies is ongoing. These include seeking specific molecules that contribute to the development and progression of DN to potentially interfere with these "molecular targets" as well as with the cellular targets within the kidney such as podocytes, which play a major role in the pathogenesis of DN...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28593583/regulating-autophagy-as-a-therapeutic-target-for-diabetic-nephropathy
#19
REVIEW
Munehiro Kitada, Yoshio Ogura, Itaru Monno, Daisuke Koya
PURPOSE OF REVIEW: Autophagy promotes cellular health in response to various cellular stresses and to changes in nutrient conditions. In this review, we focus on the role of autophagy in the pathogenesis of diabetic nephropathy and discuss the regulation of autophagy as a new therapeutic target for the suppression of diabetic nephropathy. RECENT FINDINGS: Previous studies have indicated that autophagy deficiency or insufficiency in renal cells, including podocytes, mesangial cells, endothelial cells and tubular cells, contributes to the pathogenesis of diabetic nephropathy...
July 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28554965/fetuin-a-aggravates-lipotoxicity-in-podocytes-via-interleukin-1-signaling
#20
Jana M Orellana, Kapil Kampe, Friederike Schulze, Jonas Sieber, Andreas W Jehle
Sterile inflammation is considered critical in the pathogenesis of diabetic nephropathy (DN). Here we show that Fetuin-A (FetA) or lipopolysaccharide (LPS) exacerbate palmitic acid-induced podocyte death, which is associated with a strong induction of monocyte chemoattractant protein-1 (MCP-1) and keratinocyte chemoattractant (KC). Moreover, blockage of TLR4 prevents MCP-1 and KC secretion and attenuates podocyte death induced by palmitic acid alone or combined with FetA. In addition, inhibition of interleukin-1 (IL-1) signaling by anakinra, a recombinant human IL-1Ra, or a murinized anti-IL-1β antibody attenuates the inflammatory and ultimate cell death response elicited by FetA alone or combined with palmitic acid...
May 2017: Physiological Reports
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