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Diabetic nephropathy Tubule

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https://www.readbyqxmd.com/read/28445931/high-glucose-induces-apoptosis-via-upregulation-of-bim-expression-in-proximal-tubule-epithelial-cells
#1
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
#2
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
#3
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
#4
S J H Dobbin, J R Petrie, M E J Lean, G A McKay
Hyperkalaemia is often seen in individuals with renal impairment and may be exacerbated, particularly in diabetic nephropathy, by hyporeninaemic aldosterone deficiency (type 4 renal tubular acidosis) which may, in turn, be caused or complicated by chronic interstitial nephritis or drug therapy (Table 1). Fludrocortisone is a synthetic corticosteroid with mineralocorticoid activity that increases sodium resorption and promotes potassium excretion in the distal convoluted renal tubule. It therefore seems a logical option to reverse hyperkalaemia in type 4 renal tubular acidosis; however, we can find no published guideline recommending this use [1,2]...
April 4, 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
#5
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...
March 30, 2017: Kidney International
https://www.readbyqxmd.com/read/28364255/microrna-184-is-a-downstream-effector-of-albuminuria-driving-renal-fibrosis-in-rats-with-diabetic-nephropathy
#6
Cristina Zanchi, Daniela Macconi, Piera Trionfini, Susanna Tomasoni, Daniela Rottoli, Monica Locatelli, Michael Rudnicki, Jo Vandesompele, Pieter Mestdagh, Giuseppe Remuzzi, Ariela Benigni, Carlamaria Zoja
AIMS/HYPOTHESIS: Renal fibrosis is a common complication of diabetic nephropathy and is a major cause of end-stage renal disease. Despite the suggested link between renal fibrosis and microRNA (miRNA) dysregulation in diabetic nephropathy, the identification of the specific miRNAs involved is still incomplete. The aim of this study was to investigate miRNA profiles in the diabetic kidney and to identify potential downstream targets implicated in renal fibrosis. METHODS: miRNA expression profiling was investigated in the kidneys of 8-month-old Zucker diabetic fatty (ZDF) rats during overt nephropathy...
March 31, 2017: Diabetologia
https://www.readbyqxmd.com/read/28356293/urinary-dcr2-is-a-novel-biomarker-for-tubulointerstitial-injury-in-patients-with-diabetic-nephropathy
#7
Jia Chen, Wei-Wei Zhang, Ke-Hong Chen, Li-Rong Lin, Huan-Zi Dai, Kai-Long Li, Jian-Guo Zhang, Lu-Quan Zheng, Bi-Qiong Fu, Ya-Ni He
Tubulointerstitial injury (TII) plays a crucial role in the progression of diabetic nephropathy (DN), but lack of specific and sensitive biomarkers for monitoring TII in DN management. This study is to investigate whether urinary decoy receptor 2 (uDcR2) could serve as a novel noninvasive biomarker for assessing TII in DN. We recruited 311 type 2 diabetics and 139 DN patients which diagnosed by renal biopsy. uDcR2 levels were measured by ELISA and renal DcR2 expression was detected immunohistochemically. Associations between uDcR2 and renal DcR2, renal functional parameters were evaluated...
March 29, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28325697/alcam-a-novel-biomarker-in-patients-with-type-2-diabetes-mellitus-complicated-with-diabetic-nephropathy
#8
Alba Sulaj, Stefan Kopf, Elisabeth Gröne, Hermann-Josef Gröne, Sigrid Hoffmann, Erwin Schleicher, Hans-Ulrich Häring, Vedat Schwenger, Stephan Herzig, Thomas Fleming, Peter P Nawroth, Rüdiger von Bauer
BACKGROUND & AIM: Activated leukocyte cell adhesion molecule (ALCAM/CD166) functions analogue to the receptor of advanced glycation end products, which has been implicated in the development of diabetic nephropathy (DN). We investigated the expression of ALCAM and its ligand S100B in patients with DN. METHODS: A total of 34 non-diabetic patients, 29 patients with type 2 diabetes and normal albuminuria and 107 patients with type 2 diabetes complicated with DN were assessed for serum concentration of soluble ALCAM (sALCAM) by ELISA...
January 21, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28289043/exocytosis-mediated-urinary-full-length-megalin-excretion-is-linked-with-the-pathogenesis-of-diabetic-nephropathy
#9
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/28258028/resveratrol-ameliorates-hyperglycemia-induced-renal-tubular-oxidative-stress-damage-via-modulating-the-sirt1-foxo3a-pathway
#10
Xueling Wang, Linghang Meng, Long Zhao, Zengfu Wang, Haiying Liu, Gang Liu, Guangju Guan
AIMS: Oxidative stress plays an important role in the development and progression of diabetic nephropathy (DN). We aimed to investigate if resveratrol (RSV) could ameliorate hyperglycemia-induced oxidative stress in renal tubules via modulating the SIRT1/FOXO3a pathway. METHODS: The effects of RSV on diabetes rats were assessed by periodic acid-Schiff, Masson staining, immunohistochemistry, and western blot analyses. Additionally, oxidative indicators (such as catalase, superoxide dismutase, reactive oxygen species, and malondialdehyde), the deacetylase activity of SIRT1 and protein expressions of SIRT1, FOXO3a, and acetylated-FOXO3a were measured...
December 18, 2016: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28246295/autophagy-inhibits-the-accumulation-of-advanced-glycation-end-products-by-promoting-lysosomal-biogenesis-and-function-in-the-kidney-proximal-tubules
#11
Atsushi Takahashi, Yoshitsugu Takabatake, Tomonori Kimura, Ikuko Maejima, Tomoko Namba, Takeshi Yamamoto, Jun Matsuda, Satoshi Minami, Jun-Ya Kaimori, Isao Matsui, Taiji Matsusaka, Fumio Niimura, Tamotsu Yoshimori, Yoshitaka Isaka
Advanced glycation end products (AGEs) are involved in the progression of diabetic nephropathy. AGEs filtered by glomeruli or delivered from the circulation are endocytosed and degraded in the lysosomes of kidney proximal tubular epithelial cells (PTECs). Autophagy is a highly conserved degradation system which regulates intracellular homeostasis by engulfing cytoplasmic components. We have recently demonstrated that autophagic degradation of damaged lysosomes is indispensable for cellular homeostasis in some settings...
February 28, 2017: Diabetes
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
#12
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/28149671/macrophage-tgf-%C3%AE-1-and-the-proapoptotic-extracellular-matrix-protein-bigh3-induce-renal-cell-apoptosis-in-prediabetic-and-diabetic-conditions
#13
Robert J Moritz, Richard G LeBaron, Clyde F Phelix, Rajesha Rupaimoole, Hong Seok Kim, Andrew Tsin, Reto Asmis
Metabolically stressed kidney is in part characterized by infiltrating macrophages and macrophage-derived TGF-β1 that promote the synthesis of various ECM molecules. TGF-β1 strongly enhances the expression of the gene TGFBI that encodes a cell-adhesion class, proapoptotic ECM protein called BIGH3. We hypothesized that in a diabetic environment a relationship between infiltrating macrophages, macrophage-derived TGF-β1, and BIGH3 protein promotes renal cell death. To investigate this hypothesis, we used our mouse model of diabetic complications...
July 2016: International Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28127848/mir-30c-protects-diabetic-nephropathy-by-suppressing-epithelial-to-mesenchymal-transition-in-db-db-mice
#14
Yanru Zhao, Zhongwei Yin, Huaping Li, Jiahui Fan, Shenglan Yang, Chen Chen, Dao Wen Wang
Epithelial-to-mesenchymal transition (EMT) plays a significant role in tubulointerstitial fibrosis, which is a hallmark of diabetic nephropathy. Thus, identifying the mechanisms of EMT activation could be meaningful. In this study, loss of miR-30c accompanied with increased EMT was observed in renal tubules of db/db mice and cultured HK2 cells exposed to high glucose. To further explore the roles of miR-30c in EMT and tubulointerstitial fibrosis, recombinant adeno-associated viral vector was applied to manipulate the expression of miR-30c...
April 2017: Aging Cell
https://www.readbyqxmd.com/read/28077323/high-glucose-down-regulates-microrna-181a-5p-to-increase-pro-fibrotic-gene-expression-by-targeting-early-growth-response-factor-1-in-hk-2-cells
#15
Ping Xu, Mei-Ping Guan, Jian-Gang Bi, Dan Wang, Zong-Ji Zheng, Yao-Ming Xue
Tubulointerstitial fibrosis (TIF) plays an important role in the progression of renal fibrosis in diabetic nephropathy (DN). Accumulating evidence supports a crucial effect of early growth response factor 1 (Egr1) on renal fibrosis in DN, but the underlying mechanisms are not entirely clear. Here, we explored the aggravating role of Egr1 and identified microRNA-181a-5p (miR-181a-5p) as an upstream regulator of Egr1 in TIF of DN. We demonstrated that overexpression of Egr1 enhanced, whereas small interfering RNA targeting Egr1 decreased the expressions of transforming growth factor β1 (TGF-β1) and fibrosis-related genes including fibronectin and collagen I in human proximal tubule cell line (HK-2) cells...
February 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28064277/smad2-phosphorylation-in-diabetic-kidney-tubule-epithelial-cells-is-associated-with-modulation-of-several-transforming-growth-factor-%C3%AE-family-members
#16
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
BACKGROUND: The role of transforming growth factor-β (TGF-β) has recently gained much attention in diabetic nephropathy and kidney fibrosis. In this study, we extend this to an assessment of transcriptional regulation of the entire TGF-β superfamily in kidneys from diabetic vs. healthy mice. In order to study the translation between mouse model and patients, we evaluated the signature of phosphorylated Sma- and Mad-related protein 2 (pSmad2), as molecular marker of TGF-β/activin activity, in the kidneys of streptozotocin (STZ)-treated mice compared to that of type 1 diabetes (T1D) patients...
2017: Nephron
https://www.readbyqxmd.com/read/27916082/-effects-of-ammonium-pyrrolidine-dithiocarbamate-pdtc-on-osteopontin-expression-and-autophagy-in-tubular-cells-in-streptozotocin-induced-diabetic-nephropathy-rat
#17
S Gao, J Y Jia, T K Yan, Y M Yu, W Y Shang, L Wei, Z F Zheng, P Fang, B C Chang, S Lin
Objective: To investigate the effects of ammonium pyrrolidine dithiocarbamate (PDTC) on tubulointerstitial inflammatory molecules and autophagy in diabetic nephropathy (DN) rats. Methods: Twenty-four male Sprague-Dawley rats were assigned to DN group (n=6) and DN+ PDTC group (n=6, PDTC, ip, 100 mg·kg(-1)·d(-1)), all received streptozotocin (STZ) 60 mg/kg intraperitoneally, and the other 12 rats were randomly divided into control group (n=6) and PDTC group (n=6). At the end of 12 weeks, after serum creatine (Scr) and 24-hour urinary protein were determined, rats were sacrificed to determined the renal pathological damages and the changes of nuclear factor (NF)-κB p65, p62, osteopontin (OPN), microtubule associated protein 1 light chain 3 (LC3)-Ⅱ/LC3-Ⅰ, nuclear p-NF-κB p65 by immunohistological stainning and Western blot, and ultrastructural changes of autophagic process was observed by electron microscopy (EM)...
November 29, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/27849017/elmo1-protects-renal-structure-and-ultrafiltration-in-kidney-development-and-under-diabetic-conditions
#18
Krishna Rakesh Sharma, Karl Heckler, Sandra J Stoll, Jan-Luuk Hillebrands, Katharina Kynast, Esther Herpel, Stefan Porubsky, Marlies Elger, Boris Hadaschik, Karen Bieback, Hans-Peter Hammes, Peter P Nawroth, Jens Kroll
Engulfment and cell motility 1 (ELMO1) functions as a guanine exchange factor for Rac1 and was recently found to protect endothelial cells from apoptosis. Genome wide association studies suggest that polymorphisms within human elmo1 act as a potential contributing factor for the development of diabetic nephropathy. Yet, the function of ELMO1 with respect to the glomerulus and how this protein contributes to renal pathology was unknown. Thus, this study aimed to identify the role played by ELMO1 in renal development in zebrafish, under hyperglycaemic conditions, and in diabetic nephropathy patients...
November 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27798458/the-angiotensin-type-2-receptor-and-the-kidney
#19
Antonio A B Peluso, Robson A S Santos, Thomas Unger, U Muscha Steckelings
PURPOSE OF REVIEW: Angiotensin II is a main regulator of kidney function. Renal actions mediated by the angiotensin AT1 receptor have been well known for many years. In contrast, several details of angiotensin AT2 receptor actions in kidney physiology and pathophysiology were only described very recently. These findings are reviewed in this article. RECENT FINDINGS: Regarding the role of the angiotensin AT2 receptor in kidney physiology, a major recent finding was that the AT2 receptor-mediated inhibition of Na-H exchanger-3 and Na/K-ATPase in the renal proximal tubules is caused by internalisation of these transporters, thus reducing reabsorption and increasing natriuresis/diuresis...
January 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/27777973/systems-biology-analysis-reveals-role-of-mdm2-in-diabetic-nephropathy
#20
Rintaro Saito, Anaïs Rocanin-Arjo, Young-Hyun You, Manjula Darshi, Benjamin Van Espen, Satoshi Miyamoto, Jessica Pham, Minya Pu, Simone Romoli, Loki Natarajan, Wenjun Ju, Matthias Kretzler, Robert Nelson, Keiichiro Ono, Dana Thomasova, Shrikant R Mulay, Trey Ideker, Vivette D'Agati, Ergin Beyret, Juan Carlos Izpisua Belmonte, Hans Joachim Anders, Kumar Sharma
To derive new insights in diabetic complications, we integrated publicly available human protein-protein interaction (PPI) networks with global metabolic networks using metabolomic data from patients with diabetic nephropathy. We focused on the participating proteins in the network that were computationally predicted to connect the urine metabolites. MDM2 had the highest significant number of PPI connections. As validation, significant downregulation of MDM2 gene expression was found in both glomerular and tubulointerstitial compartments of kidney biopsy tissue from 2 independent cohorts of patients with diabetic nephropathy...
October 20, 2016: JCI Insight
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