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Diabetic nephropathy Tubule

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https://www.readbyqxmd.com/read/28805677/endocytosis-of-albumin-induces-matrix-metalloproteinase-9-by-activating-the-erk-signaling-pathway-in-renal-tubule-epithelial-cells
#1
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
#2
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
#3
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...
July 26, 2017: Nephron
https://www.readbyqxmd.com/read/28725620/attenuation-of-diabetic-nephropathy-in-streptozotocin-induced-diabetic-rats-by-punica-granatum-linn-leaves-extract
#4
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
#5
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
#6
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
#7
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
#8
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)...
June 29, 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
#9
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
#10
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
#11
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/28600485/silencing-of-trb3-ameliorates-diabetic-tubule-interstitial-nephropathy-via-pi3k-akt-signaling-in-rats
#12
Yali Ma, Fang Chen, Suxia Yang, Yurui Duan, Zhiqiang Sun, Jun Shi
BACKGROUND Nephropathy, a chronic progressive kidney disease often characterized by glomeruli scarring and sclerosis, is a major complication of diabetes mellitus. Development of nephropathologic lesions has been shown to be associated with suppressed AKT phosphorylation and elevated level of apoptosis. Moreover, it has been established that the TRB3 gene is capable of inhibiting AKT phosphorylation and promoting apoptosis. MATERIAL AND METHODS In this study, we injected TRB3 siRNA into Wistar rats with type 1 diabetes, and monitored development of nephropathy in the rats...
June 10, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28587386/socs3-overexpression-inhibits-advanced-glycation-end-product-induced-emt-in-proximal-tubule-epithelial-cells
#13
Lin Yu, Ying Zhang, Huimin Zhang, Yingtao Li
Diabetic nephropathy (DN) is among the most severe complications of diabetes mellitus, and may lead to end-stage renal disease. Sustained exposure to advanced glycation end products (AGEs) typically causes renal tubular epithelial cells (TECs) to suffer from an epithelial-to-mesenchymal transition (EMT). However, there remains no consensus regarding the mechanism underlying the cause of EMT in TECs as induced by AGEs. In the present study, we investigated the promotion of EMT in TECs by AGEs, and the activation of Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling...
June 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28493961/aldosterone-signaling-regulates-the-over-expression-of-claudin-4-and-8-at-the-distal-nephron-from-type-1-diabetic-rats
#14
Eduardo Molina-Jijón, Rafael Rodríguez-Muñoz, Ricardo González-Ramírez, Carmen Namorado-Tónix, José Pedraza-Chaverri, Jose L Reyes
Hyperglycemia in diabetes alters tight junction (TJ) proteins in the kidney. We evaluated the participation of aldosterone (ALD), and the effect of spironolactone (SPL), a mineralocorticoid receptor antagonist, on the expressions of claudin-2, -4, -5 and -8, and occludin in glomeruli, proximal and distal tubules isolated from diabetic rats. Type 1 diabetes was induced in female Wistar rats by a single tail vein injection of streptozotocin (STZ), and SPL was administrated daily by gavage, from days 3-21. Twenty-one days after STZ injection the rats were sacrificed...
2017: PloS One
https://www.readbyqxmd.com/read/28484521/urinary-podocyte-associated-mrna-levels-correlate-with-proximal-tubule-dysfunction-in-early-diabetic-nephropathy-of-type-2-diabetes-mellitus
#15
Ligia Petrica, Sorin Ursoniu, Florica Gadalean, Adrian Vlad, Gheorghe Gluhovschi, Victor Dumitrascu, Daliborca Vlad, Cristina Gluhovschi, Silvia Velciov, Flaviu Bob, Petru Matusz, Oana Milas, Alina Secara, Anca Simulescu, Roxana Popescu
AIM: The study assessed mRNA expression of podocyte-associated molecules in urinary sediments of patients with type 2 diabetes mellitus (DM) in relation to urinary podocytes, biomarkers of podocyte injury and of proximal tubule (PT) dysfunction. METHODS: A total of 76 patients with type 2 DM and 20 healthy subjects were enrolled in a cross-sectional study, and assessed concerning urinary podocytes, urinary mRNA of podocyte-associated genes, urinary biomarkers of podocyte damage and of PT dysfunction...
2017: Diabetology & Metabolic Syndrome
https://www.readbyqxmd.com/read/28445931/high-glucose-induces-apoptosis-via-upregulation-of-bim-expression-in-proximal-tubule-epithelial-cells
#16
Xiao-Qian Zhang, Jian-Jun Dong, Tian Cai, Xue Shen, Xiao-Jun Zhou, Lin Liao
Diabetic nephropathy is the primary cause of end-stage renal disease. Apoptosis of tubule epithelial cells is a major feature of diabetic nephropathy. The mechanisms of high glucose (HG) induced apoptosis are not fully understood. Here we demonstrated that, HG induced apoptosis via upregulating the expression of proapoptotic Bcl-2 homology domain 3 (BH3)-only protein Bim protein, but not bring a significant change in the baseline level of autophagy in HK2 cells. The increase of Bim expression was caused by the ugregulation of transcription factors, FOXO1 and FOXO3a...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28428931/the-role-of-renal-proximal-tubule-transport-in-the-regulation-of-blood-pressure
#17
REVIEW
Shoko Horita, Motonobu Nakamura, Masashi Suzuki, Nobuhiko Satoh, Atsushi Suzuki, Yukio Homma, Masaomi Nangaku
The electrogenic sodium/bicarbonate cotransporter 1 (NBCe1) on the basolateral side of the renal proximal tubule plays a pivotal role in systemic acid-base homeostasis. Mutations in the gene encoding NBCe1 cause severe proximal renal tubular acidosis accompanied by other extrarenal symptoms. The proximal tubule reabsorbs most of the sodium filtered in the glomerulus, contributing to the regulation of plasma volume and blood pressure. NBCe1 and other sodium transporters in the proximal tubule are regulated by hormones, such as angiotensin II and insulin...
March 2017: Kidney Research and Clinical Practice
https://www.readbyqxmd.com/read/28424212/pdgf-receptor-%C3%AE-uses-akt-mtorc1-signaling-node-to-promote-high-glucose-induced-renal-proximal-tubular-cell-collagen-i-%C3%AE-2-expression
#18
Falguni Das, Nandini Ghosh-Choudhury, Balachandar Venkatesan, Balakuntalam S Kasinath, Goutam Ghosh Choudhury
Increased expression of PDGF receptor-β (PDGFRβ) has been shown in the diabetic renal proximal tubules. The core molecular network used by high glucose to induce proximal tubular epithelial cell collagen I (α2) expression is poorly understood. We hypothesized that activation of PDGFRβ by high glucose increases collagen I (α2) production via Akt/mTORC1 signaling pathway in proximal tubular epithelial cells. Using biochemical and molecular biological techniques, we investigated this hypothesis. We show that high glucose increases activating phosphorylation of the PDGFRβ, resulting in the phosphorylation of the phosphatidylinositol 3 kinase...
April 19, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28375568/fludrocortisone-therapy-for-persistent-hyperkalaemia
#19
S J H Dobbin, J R Petrie, M E J Lean, G A McKay
BACKGROUND: Type 4 renal tubular acidosis causes hyperkalaemia, for which diabetes and medications commonly used in this patient group are aetiological factors. Here we describe the novel use of fludrocortisone in this difficult condition. CASE REPORT: A 55-year-old woman with complex co-morbidities, including Type 2 diabetes (HbA1c 37 mmol/mol 5.5%), was admitted with renal failure. Bloods on admission: eGFR 25 ml/min, creatinine 184 ?mol/L, urea 35.9 mmol/L, sodium 128 mmol/L, potassium 5...
July 2017: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/28366227/fast-renal-decline-to-end-stage-renal-disease-an-unrecognized-feature-of-nephropathy-in-diabetes
#20
REVIEW
Andrzej S Krolewski, Jan Skupien, Peter Rossing, James H Warram
A new model of diabetic nephropathy in type 1 diabetes emerged from our studies of Joslin Clinic patients. The dominant feature is progressive renal decline, not albuminuria. This decline is a unidirectional process commencing while patients have normal renal function and, in the majority, progressing steadily (linearly) to end-stage renal disease (ESRD). While an individual's rate of renal decline is constant, the estimated glomerular filtration rate (eGFR) slope varies widely among individuals from -72 to -3...
June 2017: Kidney International
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