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Pathogenesis diabetic nephropathy

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https://www.readbyqxmd.com/read/28336553/tlr2-knockout-protects-against-diabetes-mediated-changes-in-cerebral-perfusion-and-cognitive-deficits
#1
Trevor Hardigan, Caterina Hernandez, Rebecca Ward, M Nasrul Hoda, Adviye Ergul
The risk of cognitive decline in diabetes (Type 1 and Type 2) is significantly greater compared to normoglycemic patients, and the risk of developing dementia in diabetic patients is doubled. The etiology for this is likely multifactorial, but one mechanism that has gained increasing attention is decreased cerebral perfusion as a result of cerebrovascular dysfunction. The innate immune system has been shown to play a role in diabetic vascular complications, notably through Toll-like receptor (TLR) stimulated release of pro-inflammatory cytokines and chemokines that leads to vascular damage...
February 22, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28319415/transforming-growth-factor-beta-1-an-important-biomarker-for-developing-cardiovascular-diseases-in-chronic-renal-failure
#2
E Avci, G Alp Avci, B Ozcelik, S Coskun Cevher, M Suicmez
OBJECTIVE: Our study focuses on the determination and evaluation of TGF-β1 levels of patients receiving hemodialysis treatment because of chronic renal failure. BACKGROUND: Chronic renal failure, characterized by irreversible loss of renal function, is a major public health problem in the world. Transforming growth factor-beta is a multifunctional cytokine involved in the cellular growth, differentiation, migration, apoptosis and immune regulation. Among the three TGF-β isoforms, TGF-β1 plays a key role in the pathogenesis of renal diseases...
2017: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/28291548/the-role-of-interleukin-17a-in-the-pathogenesis-of-kidney-diseases
#3
REVIEW
Charlotte Cortvrindt, Reinhart Speeckaert, Alena Moerman, Joris R Delanghe, Marijn M Speeckaert
Being a member of the IL-17 family, comprising six structurally related ligands, IL-17A is a cytokine, produced by multiple cell types, such as CD4(+)αβ T cells, γδ T cells, natural killer cells, neutrophils, macrophages, dendritic cells, lymphoid tissue inducer cells, mast cells and plasma cells. IL-17A participates in tissue inflammation by inducing the expression of chemokines, proinflammatory cytokines and matrix metalloproteases. Besides its role in host defence against infectious diseases, IL-17A is involved in different autoimmune and inflammatory diseases...
March 10, 2017: Pathology
https://www.readbyqxmd.com/read/28289043/exocytosis-mediated-urinary-full-length-megalin-excretion-is-linked-with-the-pathogenesis-of-diabetic-nephropathy
#4
Shankhajit De, Shoji Kuwahara, Michihiro Hosojima, Tomomi Ishikawa, Ryohei Kaseda, Piyali Sarkar, Yusuke Yoshioka, Hideyuki Kabasawa, Tomomichi Iida, Sawako Goto, Koji Toba, Yuki Higuchi, Yoshiki Suzuki, Masanori Hara, Hiroyuki Kurosawa, Ichiei Narita, Yoshiaki Hirayama, Takahiro Ochiya, Akihiko Saito
Efficient biomarkers for diabetic nephropathy (DN) have not been established. Using enzyme-linked immunosorbent assay, we found previously that urinary levels of full-length megalin (C-megalin), a multiligand endocytic receptor in proximal tubules, was positively correlated with DN progression in type 2 diabetes mellitus (T2DM). Here, we found that urinary extracellular vesicle (UEV) excretion and C-megalin content in UEVs or in their exosomal fraction increased along with the progression of the albuminuric stages in T2DM patients...
March 13, 2017: Diabetes
https://www.readbyqxmd.com/read/28283950/caveolin-1-in-the-pathogenesis-of-diabetic-nephropathy-potential-therapeutic-target
#5
REVIEW
Richard Van Krieken, Joan C Krepinsky
PURPOSE OF REVIEW: Diabetic nephropathy, a major microvascular complication of diabetes and the most common cause of end-stage renal disease, is characterized by prominent accumulation of extracellular matrix. The membrane microdomains caveolae, and their integral protein caveolin-1, play critical roles in the regulation of signal transduction. In this review we discuss current knowledge of the contribution of caveolin-1/caveolae to profibrotic signaling and the pathogenesis of diabetic kidney disease, and assess its potential as a therapeutic target...
March 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28277542/microrna-27a-promotes-podocyte-injury-via-ppar%C3%AE-mediated-%C3%AE-catenin-activation-in-diabetic-nephropathy
#6
Zhanmei Zhou, Jiao Wan, Xiaoyan Hou, Jian Geng, Xiao Li, Xiaoyan Bai
Podocyte injury has a pivotal role in the pathogenesis of diabetic nephropathy (DN). MicroRNA-27a (miR-27a), peroxisome proliferator-activated receptor γ (PPARγ) and β-catenin pathways have been involved in the pathogenesis of DN. Herein, we asked whether miR-27a mediates podocyte injury through PPARγ/β-catenin signaling in DN. The functional relevance of miR-27a, PPARγ and β-catenin were investigated in cultured podocytes and glomeruli of diabetic rats and patients using in vitro and in vivo approaches...
March 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28272773/comparative-rna-seq-transcriptome-analyses-reveal-distinct-metabolic-pathways-in-diabetic-nerve-and-kidney-disease
#7
Lucy M Hinder, Meeyoung Park, Amy E Rumora, Junguk Hur, Felix Eichinger, Subramaniam Pennathur, Matthias Kretzler, Frank C Brosius, Eva L Feldman
Treating insulin resistance with pioglitazone normalizes renal function and improves small nerve fibre function and architecture; however, it does not affect large myelinated nerve fibre function in mouse models of type 2 diabetes (T2DM), indicating that pioglitazone affects the body in a tissue-specific manner. To identify distinct molecular pathways regulating diabetic peripheral neuropathy (DPN) and nephropathy (DN), as well those affected by pioglitazone, we assessed DPN and DN gene transcript expression in control and diabetic mice with or without pioglitazone treatment...
March 8, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28271466/intestinal-microbiota-in-type-2-diabetes-and-chronic-kidney-disease
#8
REVIEW
Alice Sabatino, Giuseppe Regolisti, Carmela Cosola, Loreto Gesualdo, Enrico Fiaccadori
PURPOSE OF THE REVIEW: Diabetes mellitus is a major cause of kidney disease [chronic kidney disease (CKD) and end-stage renal disease (ESRD)] and are both characterized by an increased risk of cardiovascular events. Diabetes and kidney disease are also commonly associated with a chronic inflammatory state, which is now considered a non-traditional risk factor for atherosclerosis. In the case of type 2 diabetes mellitus (T2DM), inflammation is mainly a consequence of visceral obesity, while in the case of CKD or ESRD patients on dialysis, inflammation is caused by multiple factors, classically grouped as dialysis-related and non-dialysis-related...
March 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28262777/the-role-of-the-complement-system-in-diabetic-nephropathy
#9
REVIEW
Allan Flyvbjerg
The development of type 1 and type 2 diabetes mellitus has a substantial negative impact on morbidity and mortality and is responsible for substantial individual and socioeconomic costs worldwide. One of the most serious consequences of diabetes mellitus is the development of diabetic angiopathy, which manifests clinically as microvascular and macrovascular complications. One microvascular complication, diabetic nephropathy, is the most common cause of end-stage renal disease in developed countries. Although several available therapeutic interventions can delay the onset and progression of diabetic nephropathy, morbidity associated with this disease remains high and new therapeutic approaches are needed...
March 6, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28225005/autophagy-protects-against-palmitic-acid-induced-apoptosis-in-podocytes-in-vitro
#10
Xu-Shun Jiang, Xue-Mei Chen, Jiang-Min Wan, Hai-Bo Gui, Xiong-Zhong Ruan, Xiao-Gang Du
Autophagy is a highly conserved degradation process that is involved in the clearance of proteins and damaged organelles to maintain intracellular homeostasis and cell integrity. Type 2 diabetes is often accompanied by dyslipidemia with elevated levels of free fatty acids (FFAs). Podocytes, as an important component of the filtration barrier, are susceptible to lipid disorders. The loss of podocytes causes proteinuria, which is involved in the pathogenesis of diabetic nephropathy. In the present study, we demonstrated that palmitic acid (PA) promoted autophagy in podocytes...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28218466/bullous-pemphigoid-arising-in-a-patient-with-acquired-perforating-dermatosis
#11
S Tani, N Ishii, T Hashimoto, K Tsujioka
A middle-aged Japanese man who had been on haemodialysis treatment for diabetic nephropathy developed multiple itchy papules and nodules, which were histopathologically diagnosed as acquired perforating dermatosis. Two years later he developed oral lesions and subsequently numerous erosive plaques with necrotic crusts on the trunk and extremities. Histopathology of a papule showed a parakeratotic plug intermingled with basophilic, necrotic debris and collagen bundles, along with penetration of collagen bundles across the epidermis and subepidermal blister...
February 20, 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/28214337/palmitate-induces-mitochondrial-superoxide-generation-and-activates-ampk-in-podocytes
#12
Eugene Lee, Jin Choi, Hyun Soon Lee
Studies have shown that high levels of serum free fatty acids (FFAs) are associated with lipotoxicity and type 2 diabetes. Palmitic acid (PA) is the predominant circulating saturated FFA, yet its role in the pathogenesis of diabetic nephropathy (DN) is not clear. Recently, one study suggested that mitochondrial superoxide production is related to AMP-activated protein kinase (AMPK) activity in diabetic mice kidneys. To elucidate the link between PA and oxidative stress and AMPK activity in DN, we compared the cultured murine podocytes exposed to PA and oleic acid (OA)...
February 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28208054/high-glucose-induced-hypomethylation-promotes-binding-of-sp-1-to-myo-inositol-oxygenase-implication-in-the-pathobiology-of-diabetic-tubulopathy
#13
Isha Sharma, Rajesh K Dutta, Neel K Singh, Yashpal S Kanwar
The catabolic enzyme myo-inositol oxygenase (MIOX) is expressed in proximal tubules and up-regulated in the diabetic state. Previously, we reported its transcriptional and translation regulation by high glucose (HG), osmolytes, and fatty acids. However, its epigenetic regulation is unknown. Bisulfite sequencing revealed that both human and mouse MIOX promoters, enriched with CpG sites, are hypomethylated and unmethylated under HG ambience and hyperglycemic states associated with increased MIOX expression. Eletrophoretic mobility shift assays revealed increased binding of unmethylated oligos with nucleoproteins of cells maintained under HG...
April 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28201968/common-drugs-for-stabilization-of-renal-function-in-the-progression-of-diabetic-nephropathy-and-their-relations-with-hypertension-therapy
#14
Yuxuan Wang, Chengcheng Wang, Xiuli Zhang, Harvest F Gu, Liang Wu
Diabetic nephropathy is characterized by hypertension, progressive albuminuria, glomerulosclerosis and declines in glomerular filtration rate leading to end stage renal disease. Although the pathogenesis of diabetic nephropathy is not fully understood, current treatment of the patients with diabetic nephropathy is mainly based upon the control of hyperglycaemia and management of blood pressures. Several drugs, which are originally developed for hypertension therapy, have been adopted for stabilization of renal function in diabetic nephropathy...
February 14, 2017: Current Diabetes Reviews
https://www.readbyqxmd.com/read/28182703/nephropathy-in-pparg-null-mice-highlights-ppar%C3%AE-systemic-activities-in-metabolism-and-in-the-immune-system
#15
Barbara Toffoli, Federica Gilardi, Carine Winkler, Magnus Soderberg, Laura Kowalczuk, Yvan Arsenijevic, Krister Bamberg, Olivier Bonny, Béatrice Desvergne
Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-dependent transcription factor involved in many aspects of metabolism, immune response, and development. Total-body deletion of the two Pparg alleles provoked generalized lipoatrophy along with severe type 2 diabetes. Herein, we explore the appearance and development of structural and functional alterations of the kidney, comparing Pparg null-mice to their littermate controls (carrying Pparg floxed alleles). We show that renal hypertrophy and functional alterations with increased glucosuria and albuminuria are already present in 3 weeks-old Pparg null-mice...
2017: PloS One
https://www.readbyqxmd.com/read/28181698/calcium-uptake-via-mitochondrial-uniporter-contributes-to-palmitic-acid-induced-apoptosis-in-mouse-podocytes
#16
Zeting Yuan, Aili Cao, Hua Liu, Henjiang Guo, Yingjun Zang, Yi Wang, Yunman Wang, Hao Wang, Peihao Yin, Wen Peng
Podocytes are component cells of the glomerular filtration barrier, and their loss by apoptosis is the main cause of proteinuria that leads to diabetic nephropathy (DN). Therefore, insights into podocyte apoptosis mechanism would allow a better understanding of DN pathogenesis and thus help develop adequate therapeutic strategies. Here, we investigated the molecular mechanism of palmitic acid-inhibited cell death in mouse podocytes, and found that palmitic acid increased cell death in a dose- and time-dependent manner...
February 9, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28178159/adma-predicts-major-adverse-renal-events-in-patients-with-mild-renal-impairment-and-or-diabetes-mellitus-undergoing-coronary-angiography
#17
Fabian Heunisch, Lyubov Chaykovska, Gina von Einem, Markus Alter, Thomas Dschietzig, Axel Kretschmer, Karl-Heinz Kellner, Berthold Hocher
Asymmetric dimethylarginine (ADMA) is a competitive inhibitor of the nitric oxide (NO)-synthase and a biomarker of endothelial dysfunction (ED). ED plays an important role in the pathogenesis of contrast-induced nephropathy (CIN). The aim of our study was to evaluate serum ADMA concentration as a biomarker of an acute renal damage during the follow-up of 90 days after contrast medium (CM) application.Blood samples were obtained from 330 consecutive patients with diabetes mellitus or mild renal impairment immediately before, 24 and 48 hours after the CM application for coronary angiography...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28159318/circulating-fibronectin-contributes-to-mesangial-expansion-in-a-murine-model-of-type-1-diabetes
#18
Verena Klemis, Hiba Ghura, Giuseppina Federico, Carina Würfel, Anke Bentmann, Norbert Gretz, Tatsuhiko Miyazaki, Hermann-Joseph Gröne, Inaam A Nakchbandi
Fibronectin is ubiquitously expressed in the extracellular matrix, and its accumulation in the glomerular mesangium in diabetic nephropathy is associated with deterioration of renal function in these patients. However, the exact role of fibronectin in the pathogenesis of diabetic nephropathy remains unknown. To clarify this, we administered fluorescent-labeled plasma fibronectin to wild-type mice and found it to accumulate in the mesangium. Using liver-specific conditional-knockout mice to decrease circulating fibronectin, we reduced circulating fibronectin by more than 90%...
January 31, 2017: Kidney International
https://www.readbyqxmd.com/read/28137588/long-noncoding-rna-tug1-alleviates-extracellular-matrix-accumulation-via-mediating-microrna-377-targeting-of-ppar%C3%AE-in-diabetic-nephropathy
#19
Li-Jun Duan, Min Ding, Li-Jun Hou, Yuan-Tao Cui, Chun-Jun Li, De-Min Yu
Long noncoding RNA taurine-upregulated gene 1 (lncRNA TUG1) has been reported to play a key role in the progression of diabetic nephropathy (DN). However, the role of lncRNA TUG1 in the regulation of diabetic nephropathy remains largely unknown. The aim of the present study is to identify the regulation of lncRNA TUG1 on extracellular matrix accumulation via mediating microRNA-377 targeting of PPARγ, and investigate the underlying mechanisms in progression of DN. Microarray was performed to screen differentially expressed miRNAs in db/db DN mice...
March 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28134328/effect-of-bilirubin-concentration-on-the-risk-of-diabetic-complications-a-meta-analysis-of-epidemiologic-studies
#20
Bo Zhu, Xiaomei Wu, Yifei Bi, Yang Yang
Diabetes can affect many parts of the body and is associated with serious complications. Oxidative stress is a major contributor in the pathogenesis of diabetic complications and bilirubin has been shown to have antioxidant effects. The number of studies on the effect of bilirubin on the risk of diabetic complications has increased, but the results are inconsistent. Thus, we performed a meta-analysis to determine the relationship between bilirubin concentration and the risk of diabetic complications, and to investigate if there was a dose-response relationship...
January 30, 2017: Scientific Reports
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