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Diabetic nephropathy Tubule

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https://www.readbyqxmd.com/read/29137984/recombinant-human-glp-1-rhglp-1-alleviating-renal-tubulointestitial-injury-in-diabetic-stz-induced-rats
#1
Weiqin Yin, Shiqing Xu, Zai Wang, Honglin Liu, Liang Peng, Qing Fang, Tingting Deng, Wenjian Zhang, Jinning Lou
GLP-1-based treatment improves glycemia through stimulation of insulin secretion and inhibition of glucagon secretion. Recently, more and more findings showed that GLP-1 could also protect kidney from diabetic nephropathy. Most of these studies focused on glomeruli, but the effect of GLP-1 on tubulointerstitial and tubule is not clear yet. In this study, we examined the renoprotective effect of recombinant human GLP-1 (rhGLP-1), and investigated the influence of GLP-1 on inflammation and tubulointerstitial injury using diabetic nephropathy rats model of STZ-induced...
November 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29124787/reduced-tubular-degradation-of-glomerular-filtered-plasma-albumin-is-a-common-feature-in-acute-and-chronic-kidney-disease
#2
Yingjie Han, Nguyen D K Ly, Greg H Tesch, Philip Poronnik, David J Nikolic-Paterson
Tubular epithelial cells take up and degrade plasma albumin filtered by the glomerulus. Tubular damage resulting in reduced albumin uptake or degradation has been suggested as one mechanism contributing to albuminuria in kidney disease. This study investigated whether albumin uptake or degradation is altered in acute and chronic glomerular disease. Mouse models of acute glomerular injury (anti-GBM disease and LPS-induced albuminuria) and chronic disease (streptozotocin-induced diabetes and db/db mice) were examined...
November 10, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29070574/cell-adhesion-molecule-1-cadm1-shedding-induces-apoptosis-of-renal-epithelial-cells-and-exacerbates-human-nephropathies
#3
Takashi Kato, Man Hagiyama, Yasutoshi Takashima, Azusa Yoneshige, Akihiko Ito
Chronic kidney disease (CKD) is an important problem throughout the world, associated with the increase of blood urea nitrogen (BUN) and serum creatinine (sCre), and renal tubular injuries. It is crucial to elucidate the molecular mechanisms of renal injuries in order to identify the new therapeutics and early diagnostic methods. We focused on cell adhesion molecule-1 (CADM1) protein. CADM1, its isoform SP4, is expressed in the epithelial cells of various tissues including renal distal tubules, localized on the lateral cell membrane, mediates cell-cell adhesion via trans-homophilic binding, and interacts with various proteins...
October 25, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29030466/modulation-of-renal-glut2-by-the-cannabinoid-1-receptor-implications-for-the-treatment-of-diabetic-nephropathy
#4
Liad Hinden, Shiran Udi, Adi Drori, Asaad Gammal, Alina Nemirovski, Rivka Hadar, Saja Baraghithy, Anna Permyakova, Matan Geron, Merav Cohen, Sabina Tsytkin-Kirschenzweig, Yael Riahi, Gil Leibowitz, Yaakov Nahmias, Avi Priel, Joseph Tam
Altered glucose reabsorption via the facilitative glucose transporter 2 (GLUT2) during diabetes may lead to renal proximal tubule cell (RPTC) injury, inflammation, and interstitial fibrosis. These pathologies are also triggered by activating the cannabinoid-1 receptor (CB1R), which contributes to the development of diabetic nephropathy (DN). However, the link between CB1R and GLUT2 remains to be determined. Here, we show that chronic peripheral CB1R blockade or genetically inactivating CB1Rs in the RPTCs ameliorated diabetes-induced renal structural and functional changes, kidney inflammation, and tubulointerstitial fibrosis in mice...
October 13, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28929120/sulodexide-protects-renal-tubular-epithelial-cells-from-oxidative-stress-induced-injury-via-upregulating-klotho-expression-at-an-early-stage-of-diabetic-kidney-disease
#5
Yu Ning Liu, Jingwei Zhou, Tingting Li, Jing Wu, Shu Hua Xie, Hua-Feng Liu, Zhangsuo Liu, Tae Sun Park, Yaoxian Wang, Wei Jing Liu
The hypoalbuminuric effect of sulodexide (SDX) on diabetic kidney disease (DKD) was suggested by some clinical trials but was denied by the Collaborative Study Group. In this study, the diabetic rats were treated with SDX either from week 0 to 24 or from week 13 to 24. We found that 24-week treatment significantly decreased the urinary protein and HAVCR1 excretion, inhibited the interstitial expansion, and downregulated the renal cell apoptosis and interstitial fibrosis. Renoprotection was also associated with a reduction in renocortical/urinary oxidative activity and the normalization of renal klotho expression...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28860163/proximal-tubular-cannabinoid-1-receptor-regulates-obesity-induced-ckd
#6
Shiran Udi, Liad Hinden, Brian Earley, Adi Drori, Noa Reuveni, Rivka Hadar, Resat Cinar, Alina Nemirovski, Joseph Tam
Obesity-related structural and functional changes in the kidney develop early in the course of obesity and occur independently of hypertension, diabetes, and dyslipidemia. Activating the renal cannabinoid-1 receptor (CB1R) induces nephropathy, whereas CB1R blockade improves kidney function. Whether these effects are mediated via a specific cell type within the kidney remains unknown. Here, we show that specific deletion of CB1R in the renal proximal tubule cells did not protect the mice from obesity, but markedly attenuated the obesity-induced lipid accumulation in the kidney and renal dysfunction, injury, inflammation, and fibrosis...
August 31, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28852907/functional-role-of-suv39h1-in-human-renal-tubular-epithelial-cells-under-high-glucose-ambiance
#7
Jiayi Wang, Wenzhe Yan, Xiaofei Peng, Yafeng Jiang, Liyu He, Youming Peng, Xian Chen, Muyao Ye, Hui Zhuo
SUV39H1, the histone methyltransferase (HMTase) of histone H3 lysine 9 trimethylation (H3K9me3), is a known transcriptional repressor of inflammatory genes. The effect of SUV39H1 on inflammatory gene promoters under high-glucose stimulation in vascular smooth muscle cells (VSMCs), macrophages, and cardiomyocytes has been studied, but how SUV39H1 functions in renal tubules under diabetic conditions is unclear. Renal biopsy specimens of ten diabetic nephropathy (DN) subjects and seven non-DN minimal change diseases (MCD) subjects were collected...
August 29, 2017: Inflammation
https://www.readbyqxmd.com/read/28840540/a-more-tubulocentric-view-of-diabetic-kidney-disease
#8
REVIEW
Letizia Zeni, Anthony G W Norden, Giovanni Cancarini, Robert J Unwin
Diabetic nephropathy (DN) is a common complication of Diabetes Mellitus (DM) Types 1 and 2, and prevention of end stage renal disease (ESRD) remains a major challenge. Despite its high prevalence, the pathogenesis of DN is still controversial. Initial glomerular disease manifested by hyperfiltration and loss of glomerular size and charge permselectivity may initiate a cascade of injuries, including tubulo-interstitial disease. Clinically, 'microalbuminuria' is still accepted as an early biomarker of glomerular damage, despite mounting evidence that its predictive value for DN is questionable, and findings that suggest the proximal tubule is an important link in the development of DN...
August 24, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28819999/high-glucose-induces-hgf-independent-activation-of-met-receptor-in-human-renal-tubular-epithelium
#9
Lucia Mesarosova, Peter Ochodnicky, Jaklien C Leemans, Sandrine Florquin, Peter Krenek, Jan Klimas
CONTEXT: The role of hepatocyte growth factor (HGF) in diabetic kidney damage remains controversial. OBJECTIVE: To test the hypothesis that high glucose levels activate pathways related to HGF and its receptor Met and that this could participate in glucose-induced renal cell damage. MATERIALS AND METHODS: HK2 cells, a human proximal tubule epithelial cell line, were stimulated with high glucose for 48 hours. Levels of pMet/Met, pEGFR/EGFR, pSTAT3/STAT3, pAkt/Akt and pERK1/2/ERK1/2 were studied by immunoblotting...
August 18, 2017: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/28805677/endocytosis-of-albumin-induces-matrix-metalloproteinase-9-by-activating-the-erk-signaling-pathway-in-renal-tubule-epithelial-cells
#10
Xiaoming Chen, Alyssa Cobbs, Jasmine George, Ashmeer Chima, Fidele Tuyishime, Xueying Zhao
Matrix metalloproteinase-9 (MMP-9) is dysregulated in chronic kidney diseases including diabetic nephropathy. This study was performed to examine the expression of MMP-9 in renal tubule epithelial cells (TECs) under diabetic conditions and its regulatory mechanisms. We characterized MMP-9 protein in diabetic animals and primary cultured rat TECs exposed to exogenous albumin and high glucose. We also used specific inhibitors to determine if internalization of albumin and/or extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation were required for MMP-9 secretion...
August 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28805484/disparate-phospho-smad2-levels-in-advanced-type-2-diabetes-patients-with-diabetic-nephropathy-and-early-experimental-db-db-mouse-model
#11
Lise Høj Thomsen, Morten Fog-Tonnesen, Lisbeth Nielsen Fink, Jenny Norlin, Amaya García de Vinuesa, Troels Krarup Hansen, Emile de Heer, Peter Ten Dijke, Alexander Rosendahl
Uncontrolled activation of transforming growth factor beta (TGF-β) family members is hypothesized to participate in type 2 diabetes (T2D) dependent diabetic nephropathy (DN). We evaluated and compared downstream activation of the Smad2-signaling pathway in kidney samples from T2D patients to kidneys from the T2D model of leptin receptor deficient db/db mouse. Furthermore, expression of TGF-β family members was evaluated to elucidate molecular mechanisms in the mouse model. Kidney samples from patients with advanced stages of DN showed elevated pSmad2 staining whereas db/db mouse kidneys surprisingly showed a decrease in pSmad2 in the tubular compartment...
November 2017: Renal Failure
https://www.readbyqxmd.com/read/28743130/sglt-2-inhibition-a-potential-new-treatment-for-diabetic-kidney-disease
#12
Robert D Toto
Diabetic nephropathy is the leading cause of kidney failure. Treatments with drugs that block the renin-angiotensin system have proven beneficial in slowing kidney disease progression among those with diabetes; their benefit is limited and they do not stop disease progression. Despite multiple clinical trials of various interventions including dual blockade of the renin-angiotensin system over the past 15 years, no new therapies have emerged to slow kidney disease progression in diabetes. SGLT-2 inhibitors are a new class of antiglycemic drugs that have been shown to lower blood glucose by inhibition of the sodium-glucose transporter 2 in the proximal tubule of the kidney...
2017: Nephron
https://www.readbyqxmd.com/read/28725620/attenuation-of-diabetic-nephropathy-in-streptozotocin-induced-diabetic-rats-by-punica-granatum-linn-leaves-extract
#13
Snehal Nitin Mestry, Jayesh Bachu Dhodi, Sangita Balbhim Kumbhar, Archana Ramesh Juvekar
With an objective to develop Complementary and Alternative Medicine for the treatment of diabetic nephropathy, the present study investigated the protective effects of methanolic extract of Punica granatum leaves (MPGL) in streptozotocin-induced diabetic nephropathy. Diabetic nephropathy has become a leading cause of end stage renal failure worldwide. P. granatum, due to its anti-diabetic, anti-inflammatory and antioxidant activities may retard the progression of diabetic nephropathy. In this study, diabetes was induced by a single injection of streptozotocin (STZ, 45 mg/kg, i...
July 2017: Journal of Traditional and Complementary Medicine
https://www.readbyqxmd.com/read/28707079/down-regulation-of-mir-23a-inhibits-high-glucose-induced-emt-and-renal-fibrogenesis-by-up-regulation-of-snon
#14
Haiping Xu, Fuyun Sun, Xiuli Li, Lina Sun
It has been reported that transforming growth factor-β1 (TGF-β1) signaling plays an important role in the development of diabetic nephropathy (DN). The nuclear transcription co-repressor Ski-related novel protein N (SnoN) is a critical negative regulator of TGF-β1/Smad signal pathway, involving in tubule epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) accumulation, and tubulointerstitial fibrosis. In this study, we focused on miR-23a as a regulator of SnoN. Our purpose is to study the effects of miR-23a on high glucose (HG)-induced EMT process and ECM deposition in HK2 cells...
July 13, 2017: Human Cell
https://www.readbyqxmd.com/read/28676554/diabetic-rats-present-higher-urinary-loss-of-proteins-and-lower-renal-expression-of-megalin-cubilin-clc-5-and-cftr
#15
Miriam F Figueira, Raquel C Castiglione, Carolina M de Lemos Barbosa, Felipe M Ornellas, Geórgia da Silva Feltran, Marcelo M Morales, Rodrigo N da Fonseca, Jackson de Souza-Menezes
Diabetic nephropathy (DN) occurs in around 40% of those with diabetes. Proteinuria is the main characteristic of DN and develops as a result of increased permeability of the glomerulus capillary wall and/or decreased proximal tubule endocytosis. The goal of this work was to evaluate renal function and the expression of megalin, cubilin, CFTR (cystic fibrosis transmembrane conductance regulator), and ClC-5 in the proximal tubule and renal cortex of rats with type 1 diabetes. Male Wistar rats were randomly assigned to control (CTRL) and diabetic (DM) groups for 4 weeks...
July 2017: Physiological Reports
https://www.readbyqxmd.com/read/28671608/lipotoxicity-induced-prmt1-exacerbates-mesangial-cell-apoptosis-via-endoplasmic-reticulum-stress
#16
Min-Jung Park, Ho Jae Han, Dong-Il Kim
Lipotoxicity-induced mesangial cell apoptosis is implicated in the exacerbation of diabetic nephropathy (DN). Protein arginine methyltransferases (PRMTs) have been known to regulate a variety of biological functions. Recently, it was reported that PRMT1 expression is increased in proximal tubule cells under diabetic conditions. However, their roles in mesangial cells remain unexplored. Thus, we examined the pathophysiological roles of PRMTs in mesangial cell apoptosis. Treatment with palmitate, which mimics cellular lipotoxicity, induced mesangial cell apoptosis via protein kinase RNA-like endoplasmic reticulum kinase (PERK) and ATF6-mediated endoplasmic reticulum (ER) stress signaling...
July 3, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28663230/tissue-specific-microrna-expression-patterns-in-four-types-of-kidney-disease
#17
COMPARATIVE STUDY
Maria Angeles Baker, Seth J Davis, Pengyuan Liu, Xiaoqing Pan, Anna Marie Williams, Kenneth A Iczkowski, Sean T Gallagher, Kaylee Bishop, Kevin R Regner, Yong Liu, Mingyu Liang
MicroRNAs contribute to the development of kidney disease. Previous analyses of microRNA expression in human kidneys, however, were limited by tissue heterogeneity or the inclusion of only one pathologic type. In this study, we used laser-capture microdissection to obtain glomeruli and proximal tubules from 98 human needle kidney biopsy specimens for microRNA expression analysis using deep sequencing. We analyzed specimens from patients with diabetic nephropathy (DN), FSGS, IgA nephropathy (IgAN), membranoproliferative GN (MPGN) (n=19-23 for each disease), and a control group (n=14)...
October 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28659153/advanced-glycation-end-products-ages-increase-renal-lipid-accumulation-a-pathogenic-factor-of-diabetic-nephropathy-dn
#18
Yang Yuan, Hong Sun, Zilin Sun
BACKGROUND: Advanced glycation end products (AGEs) are pathogenic factors of diabetic nephropathy (DN), causing renal damage in various ways. The aim of this study is to investigate the ectopic lipid accumulation caused by AGEs in human renal tubular epithelial cell line (HK-2) cells and the kidney of type 2 diabetic rats. METHODS: In vivo study, diabetes was induced in male Sprague-Dawley rats through intraperitoneal injection of high-fat/high-sucrose diet and low-dose streptozocin (STZ)...
June 28, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28640832/sarpogrelate-hydrochloride-ameliorates-diabetic-nephropathy-associated-with-inhibition-of-macrophage-activity-and-inflammatory-reaction-in-db-db-mice
#19
Eun Soo Lee, Mi Young Lee, Mi-Hye Kwon, Hong Min Kim, Jeong Suk Kang, You Mi Kim, Eun Young Lee, Choon Hee Chung
The aim of this study was to evaluate the effects of sarpogrelate hydrochloride (SH), a selective serotonin 2A receptor antagonist, on diabetic nephropathy in a type 2 diabetes mouse model. We treated db/m and db/db mice with SH (30 mg/kg/day) for 12 weeks. Rat renal proximal tubule cells (NRK-52E) and mouse macrophages (Raw 264.7) were stimulated by high glucose (30 mM glucose) or LPS (100 ng/ml) with or without SH (20 μM). We found that SH treatment increased serum adiponectin level and decreased urinary albumin, macrophage infiltration to glomeruli, and renal inflammatory and fibrosis signals, which were highly expressed in diabetic mice...
2017: PloS One
https://www.readbyqxmd.com/read/28626027/selective-activation-of-epidermal-growth-factor-receptor-in-renal-proximal-tubule-induces-tubulointerstitial-fibrosis
#20
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 (hHB-EGF), in renal proximal tubule epithelium. hHB-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...
October 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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