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Diabetic nephropathy Tubule

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https://www.readbyqxmd.com/read/29779708/imaging-mass-spectrometry-reveals-direct-albumin-fragmentation-within-the-diabetic-kidney
#1
Kerri J Grove, Nichole M Lareau, Paul A Voziyan, Fenghua Zeng, Raymond C Harris, Billy G Hudson, Richard M Caprioli
Albumin degradation in the renal tubules is impaired in diabetic nephropathy such that levels of the resulting albumin fragments increase with the degree of renal injury. However, the mechanism of albumin degradation is unknown. In particular, fragmentation of the endogenous native albumin has not been demonstrated in the kidney and the enzymes that may contribute to fragmentation have not been identified. To explore this we utilized matrix-assisted laser desorption/ionization imaging mass spectrometry for molecular profiling of specific renal regions without disturbing distinct tissue morphology...
May 17, 2018: Kidney International
https://www.readbyqxmd.com/read/29778909/n-acetylcysteine-protects-against-diabetic-nephropathy-through-control-of-oxidative-and-nitrosative-stress-by-recovery-of-nitric-oxide-in-rats
#2
Guilherme B Nogueira, Giovana R Punaro, Clemerson S Oliveira, Fabiane R Maciel, Thamires O Fernandes, Deyse Y Lima, Adelson M Rodrigues, Margaret G Mouro, Sergio R R Araujo, Elisa M S Higa
The diabetes mellitus (DM) induces several changes, with substantial increase of reactive oxygen species (ROS). The ROS cause damage to systemic and renal microvasculature, which could be one of the mechanisms involved in the development of diabetic nephropathy (DN). The ROS modulate other substances like the nitric oxide (NO), a vasodilator with important role in the renal function. N-acetylcysteine (NAC) is an antioxidant that acts replenishing intracellular cysteine levels, which is essential for glutathione formation...
May 17, 2018: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/29769449/fatty-acid-receptor-modulator-pbi-4050-inhibits-kidney-fibrosis-and-improves-glycemic-control
#3
Yan Li, Sungjin Chung, Zhilian Li, Jessica M Overstreet, Lyne Gagnon, Brigitte Grouix, Martin Leduc, Pierre Laurin, Ming-Zhi Zhang, Raymond C Harris
Extensive kidney fibrosis occurs in several types of chronic kidney diseases. PBI-4050, a potentially novel first-in-class orally active low-molecular weight compound, has antifibrotic and antiinflammatory properties. We examined whether PBI-4050 affected the progression of diabetic nephropathy (DN) in a mouse model of accelerated type 2 diabetes and in a model of selective tubulointerstitial fibrosis. eNOS-/- db/db mice were treated with PBI-4050 from 8-20 weeks of age (early treatment) or from 16-24 weeks of age (late treatment)...
May 17, 2018: JCI Insight
https://www.readbyqxmd.com/read/29760122/perturbations-in-mitochondrial-dynamics-by-p66shc-lead-to-renal-tubular-oxidative-injury-in-human-diabetic-nephropathy
#4
Ming Zhan, Irtaza Usman, Jingbo Yu, Liemin Ruan, Xueyan Bian, Jun Yang, Shikun Yang, Lin Sun, Yashpal S Kanwar
Renal tubular injury is increasingly being recognized as an early characteristic of diabetic nephropathy (DN). Mitochondrial dynamic alterations and redox protein p66Shc-mediated oxidative stress are both critical for ensuing diabetic tubular cell injury and apoptosis; whether these two processes are interlinked remains unclear. In this study, we observed changes in mitochondrial morphology and expression of associated proteins in tubules of patients with DN. We demonstrated mitochondrial fragmentation as an important pathogenic feature of tubular cell injury that is linked to oxidative stress and p66Shc up-regulation...
May 14, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29700792/preventive-effect-of-shenkang-injection-against-high-glucose-induced-senescence-of-renal-tubular-cells
#5
Biqiong Fu, Jie Yang, Jia Chen, Lirong Lin, Kehong Chen, Weiwei Zhang, Jianguo Zhang, Yani He
Shenkang injection (SKI) is a classic prescription composed of Radix Astragali, rhubarb, Astragalus, Safflower, and Salvia. This treatment was approved by the State Food and Drug Administration of China in 1999 for treatment of chronic kidney diseases based on good efficacy and safety. This study aimed to investigate the protective effect of SKI against high glucose (HG)-induced renal tubular cell senescence and its underlying mechanism. Primary renal proximal tubule epithelial cells were cultured in (1) control medium (control group), medium containing 5 mmol/L glucose; (2) mannitol medium (mannitol group), medium containing 5 mmol/L glucose, and 25 mmol/L mannitol; (3) HG medium (HG group) containing 30 mmol/L glucose; (4) SKI treatment at high (200 mg/L), medium (100 mg/L), or low (50 mg/L) concentration in HG medium (HG + SKI group); or (5) 200 mg/L SKI treatment in control medium (control + SKI group) for 72 h...
April 25, 2018: Frontiers of Medicine
https://www.readbyqxmd.com/read/29660027/the-6-hydroxychromanol-derivative-sul-109-ameliorates-renal-injury-after-deep-hypothermia-and-rewarming-in-rats
#6
Pieter C Vogelaar, Maurits Roorda, Edwin L de Vrij, Martin C Houwertjes, Maaike Goris, Hjalmar Bouma, Adrianus C van der Graaf, Guido Krenning, Robert H Henning
Background: Mitochondrial dysfunction plays an important role in kidney damage in various pathologies, including acute and chronic kidney injury and diabetic nephropathy. In addition to the well-studied ischaemia/reperfusion (I/R) injury, hypothermia/rewarming (H/R) also inflicts acute kidney injury. Substituted 6-hydroxychromanols are a novel class of mitochondrial medicines that ameliorate mitochondrial oxidative stress and protect the mitochondrial network. To identify a novel 6-hydroxychromanol that protects mitochondrial structure and function in the kidney during H/R, we screened multiple compounds in vitro and subsequently assessed the efficacy of the 6-hydroxychromanol derivatives SUL-109 and SUL-121 in vivo to protect against kidney injury after H/R in rats...
April 11, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29604259/lectin-induced-renal-local-complement-activation-is-involved-in-tubular-interstitial-injury-in-diabetic-nephropathy
#7
Jing-Min Zheng, Xian-Guo Ren, Zuan-Hong Jiang, De-Jun Chen, Wen-Jin Zhao, Li-Juan Li
BACKGROUND: Complement has been suggested to be involved in diabetic nephropathy (DN), but the exact significance and underlying mechanisms remain unclear. Data about renal local complement activation in DN patients is scarce. The purpose of the study was to clarify the significance and mechanism of renal local complement activation in DN. METHODS: Sixty-two biopsy-proven DN patients were recruited. Renal expression of C1Q, factor B, C5b-9, MBL and MBL-associated serine protease 1 (MASP1) were detected and associated with the kidney damage...
March 28, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29593848/saturated-fatty-acids-bound-to-albumin-enhance-osteopontin-expression-and-cleavage-in-renal-proximal-tubular-cells
#8
Alyssa Cobbs, Kristopher Ballou, Xiaoming Chen, Jasmine George, Xueying Zhao
Osteopontin (OPN) is one of the proinflammatory cytokines upregulated in the kidneys of diabetic animals and patients with nephropathy. An increase in urinary albumin and albumin-bound fatty acids (FA) presents a proinflammatory environment to the proximal tubules in proteinuric kidney diseases including diabetic nephropathy. This study was designed to examine if FA overload could stimulate OPN expression and cleavage in renal tubule epithelial cells. OPN gene and protein expression was examined in the kidney of Zucker diabetic (ZD) rats and cultured proximal tubular cells exposed to either bovine serum albumin (BSA) or BSA conjugated with palmitic acid (PA), the most abundant saturated plasma FA...
2018: International Journal of Physiology, Pathophysiology and Pharmacology
https://www.readbyqxmd.com/read/29587265/transforming-growth-factor-beta-1-drives-a-switch-in-connexin-mediated-cell-to-cell-communication-in-tubular-cells-of-the-diabetic-kidney
#9
Claire Hills, Gareth William Price, Mark John Wall, Timothy John Kaufmann, Sidney Chi-Wai Tang, Wai Han Yiu, Paul Edward Squires
BACKGROUND/AIMS: Changes in cell-to-cell communication have been linked to several secondary complications of diabetes, but the mechanism by which connexins affect disease progression in the kidney is poorly understood. This study examines a role for glucose-evoked changes in the beta1 isoform of transforming growth factor (TGFβ1), on connexin expression, gap-junction mediated intercellular communication (GJIC) and hemi-channel ATP release from tubular epithelial cells of the proximal renal nephron...
March 26, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29580581/acute-kidney-injury-and-progression-of-diabetic-kidney-disease
#10
REVIEW
Samuel Mon-Wei Yu, Joseph V Bonventre
Diabetic kidney disease, commonly termed diabetic nephropathy (DN), is the most common cause of end-stage kidney disease (ESKD) worldwide. The characteristic histopathology of DN includes glomerular basement membrane thickening, mesangial expansion, nodular glomerular sclerosis, and tubulointerstitial fibrosis. Diabetes is associated with a number of metabolic derangements, such as reactive oxygen species overproduction, hypoxic state, mitochondrial dysfunction, and inflammation. In the past few decades, our knowledge of DN has advanced considerably although much needs to be learned...
March 2018: Advances in Chronic Kidney Disease
https://www.readbyqxmd.com/read/29549584/acetylshikonin-from-zicao-ameliorates-renal-dysfunction-and-fibrosis-in-diabetic-mice-by-inhibiting-tgf-%C3%AE-1-smad-pathway
#11
Zezhao Li, Zhen Hong, Zhiqing Peng, Yongcai Zhao, Rusheng Shao
Diabetic nephropathy (DN) is the major cause of end-stage renal disease in diabetic patients. Zicao, a well-known Chinese traditional medicine, has attracted much attention due to its beneficial effects in various medical fields. In this study, we attempted to investigate the effects and mechanisms of action of acetylshikonin, the main ingredient of Zicao, on renal dysfunction in DN. Our results showed that administration with acetylshikonin not only decreased blood urea nitrogen, urine creatinine and the mean kidney-to-body weight ratio in streptozotocin-induced diabetic mice, but also restored the loss of body weight, whereas the blood glucose was not changed...
March 17, 2018: Human Cell
https://www.readbyqxmd.com/read/29540159/a-cross-sectional-study-on-the-relationship-between-hematological-data-and-quantitative-morphological-indices-from-kidney-biopsies-in-different-glomerular-diseases
#12
Michelangelo Nigro, Davide Viggiano, Vincenzo Ragone, Tiziana Trabace, Annamaria di Palma, Michele Rossini, Giovambattista Capasso, Loreto Gesualdo, Giuseppe Gigliotti
BACKGROUND: The classical approach to the analysis of kidney biopsies is based on semi-quantitative scores of the amount of sclerosis, inflammatory infiltrate, fibrosis and vascular damage. However, advanced renal lesions may be accompanied by a paucity of clinical features and, conversely, important clinical abnormalities may be accompanied by minimal histopathological changes. The objective of this study is to correlate new, semiautomatic, quantitative features of kidney biopsies (e...
March 14, 2018: BMC Nephrology
https://www.readbyqxmd.com/read/29539618/non-proximal-renal-tubule-derived-urinary-exosomal-mir-200b-as-a-biomarker-of-renal-fibrosis
#13
Yanting Yu, Feng Bai, Nan Qin, Wenjin Liu, Qi Sun, Yang Zhou, Junwei Yang
BACKGROUND: Renal fibrosis is a common outcome of nearly all kinds of chronic kidney disease (CKD) and eventually progresses to end-stage renal disease. The identification of an optimal biomarker of renal fibrosis to replace the invasive renal biopsy will have important clinical implications. METHODS: We isolated urinary exosomes from 50 participants and examined the exosomal protein content and particle number in 38 CKD patients with different degrees of renal fibrosis and in 12 normal individuals...
March 14, 2018: Nephron
https://www.readbyqxmd.com/read/29522878/quantification-of-molecular-heterogeneity-in-kidney-tissue-by-targeted-proteomics
#14
K Johanna R Hoyer, Sebastian Dittrich, Malte P Bartram, Markus M Rinschen
Renal diseases are driven by alterations in the entity of proteins within the kidney, at the level of single cells, nephron subunits (such as glomerulus and tubule), tissues and body fluids. Histologically, kidney diseases are extremely heterogeneous. Mass-spectrometry based proteomics provides a unique opportunity to interrogate heterogeneity and dynamics of various proteome layers within the kidney to better understand physiology and pathophysiology, and to translate signaling networks into therapies. Yet, the success of this endeavor will largely depend on improving proteomic data acquisition methods toward increased reproducibility...
March 6, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29506055/changes-in-expression-of-special-at-rich-sequence-binding-protein-1-and-phosphatase-and-tensin-homologue-in-kidneys-of-diabetic-rats-during-ageing
#15
Ivana Kristina Delic Jukic, Sandra Kostic, Natalija Filipovic, Larissa Gudelj Ensor, Marijeta Ivandic, Josefina Josipa Dukic, Marija Vitlov Uljevic, Lejla Ferhatovic Hamzic, Livia Puljak, Katarina Vukojevic
Background: Diabetic nephropathy (DN) is a common complication of diabetes mellitus (DM). We studied the expression of special AT-rich sequence binding protein 1 (SATB1) and phosphatase and tensin homologue (PTEN) in the kidneys of diabetic rats during ageing. Methods: Male Sprague Dawley rats were injected with 55 mg/kg streptozotocin (STZ) (DM group) or with citrate buffer (control group). Kidneys were collected after 2 weeks, 6 months and 12 months, and were analysed in three different kidney structures: glomeruli, proximal (PCT) and distal convoluted tubules (DCT)...
March 1, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29482336/advanced-oxidation-protein-products-aggravate-tubulointerstitial-fibrosis-through-protein-kinase-c-dependent-mitochondrial-injury-in-early-diabetic-nephropathy
#16
Xiao Li, Liting Xu, Xiaoyan Hou, Jian Geng, Jianwei Tian, Xiaoting Liu, Xiaoyan Bai
AIMS: Diabetic nephropathy (DN) is the most common microvascular complications and the principal cause of mortality and morbidity rates in patients with diabetes. The expression of advanced oxidation protein products (AOPPs) has been found in vacuolated renal tubules in DN and correlated with patients' decreased renal function. The accumulation of AOPPs is regarded as an initiating factor in podocyte injuries via the protein kinase C (PKC) signaling, which plays a critical role in triggering oxidative stress and mitochondrial injuries in diseases including DN...
May 2, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29415951/high-fructose-diet-feeding-accelerates-diabetic-nephropathy-in-spontaneously-diabetic-torii-sdt-rats
#17
Kaoru Toyoda, Yusuke Suzuki, Kyotaka Muta, Taku Masuyama, Kochi Kakimoto, Akio Kobayashi, Toshiyuki Shoda, Shoichiro Sugai
Diabetic nephropathy (DN) is one of the complications of diabetes and is now the most common cause of end-stage renal disease. Fructose is a simple carbohydrate that is present in fruits and honey and is used as a sweetener because of its sweet taste. Fructose has been reported to have the potential to progress diabetes and DN in humans even though fructose itself does not increase postprandial plasma glucose levels. In this study, we investigated the effects of high fructose intake on the kidney of the Spontaneously Diabetic Torii (SDT) rats which have renal lesions similar to those in DN patients and compared these with the effects in normal SD rats...
2018: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29409856/crocin-mediated-amelioration-of-oxidative-burden-and-inflammatory-cascade-suppresses-diabetic-nephropathy-progression-in-diabetic-rats
#18
Hadeer O Abou-Hany, Hoda Atef, Eman Said, Hassan A Elkashef, Hatem A Salem
Diabetic Nephropathy (DN) is one of the main complications associated with diabetes mellitus. Persistently elevated blood glucose level drives histopathological changes in renal tissues that hinder normal kidney functions. In the current study, crocin; the main bioactive constituent of Crocus sativus was investigated as a reno-protective agent against DN by virtue of its numerous pharmacological activities. Diabetes was induced in male Sprague-Dawely rats through intravenous injection of streptozocin (STZ) (50 mg/kg), DN was confirmed eight weeks post diabetes induction...
March 25, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29371016/high-glucose-up-regulates-microrna-34a-5p-to-aggravate-fibrosis-by-targeting-sirt1-in-hk-2-cells
#19
Meng Xue, Yang Li, Fang Hu, Yi-Jie Jia, Zong-Ji Zheng, Ling Wang, Yao-Ming Xue
Tubulointerstitial fibrosis (TIF) is crucial in the development of renal fibrosis in diabetic nephropathy(DN). Previous data shows that SIRT1 plays an important role on fibrosis, but the effect on TIF in DN and underlying mechanisms remains uncertain. In this study, we evaluated the vital role of SIRT1 and identified SIRT1 as a downstream target gene of microRNA-34a-5p (miR-34a-5p) in TIF of DN. The result revealed that expression of miR-34a-5p, fibronectin(FN),collagen type I (COL1) and transforming growth factor β1 (TGF-β1) were up-regulated accompanied by the corresponding down-regulation of SIRT1 in renal tissues of high fat diet and streptozotocin(HFD/STZ)induced diabetic mice with DN, and that the SIRT1 mRNA level was negatively correlated with miR-34a-5p expression in high glucose stimulated human proximal tubule cell line(HK-2) cells...
March 25, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29311680/inhibition-of-insulin-resistance-by-pge1-via-autophagy-dependent-fgf21-pathway-in-diabetic-nephropathy
#20
Wei Wei, Xing-Rong An, Shi-Jie Jin, Xiao-Xue Li, Ming Xu
Insulin resistance is a critical process in the initiation and progression of diabetic nephropathy (DN). Alprostadil (Prostaglandin E1, PGE1) had protective effects on renal function. However, it is unknown whether PGE1 inhibited insulin resistance in renal tubule epithelial cells via autophagy, which plays a protective role in DN against insulin resistance. Insulin resistance was induced by palmitic acid (PA) in human HK-2 cells, shown as the decrease of insulin-stimulated AKT phosphorylation, glucose transporter-4 (GLUT4), glucose uptake and enhanced phosphorylation of insulin receptor substrate 1(IRS-1) at site serine 307 (pIRS-1ser307) and downregulated expression of IRS-1...
January 8, 2018: Scientific Reports
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