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Pathogenesis diabetic nephropathy

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https://www.readbyqxmd.com/read/27904696/a-study-on-the-correlation-between-mthfr-promoter-methylation-and-diabetic-nephropathy
#1
Xiao-Hui Yang, Ren-Fang Cao, Yang Yu, Miao Sui, Tao Zhang, Jing-Yi Xu, Xiao-Mei Wang
OBJECTIVE: In order to observe the relationship between MTHFR promoter and DN, the determinations on MTHFR promoter methylation level and expression of HCY from DN patients have been carried out. METHODS: According to the Diabetes diagnosis and classification standard from WHO in 1999, 85 patients with DM diagnosed by Endocrinology and 30 healthy participants from our medical examination center were chosen as control specimen to study in this paper. All this specimen were divided into A, B, C and D four groups , which are corresponding simple diabetes mellitus group (SDM), early diabetic nephropathy group (EDN), clinical diabetic nephropathy group (CDN) and normal control group...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27882943/metadherin-facilitates-podocyte-apoptosis-in-diabetic-nephropathy
#2
Wen-Ting Liu, Fen-Fen Peng, Hong-Yu Li, Xiao-Wen Chen, Wang-Qiu Gong, Wen-Jing Chen, Yi-Hua Chen, Pei-Lin Li, Shu-Ting Li, Zhao-Zhong Xu, Hai-Bo Long
Apoptosis, one of the major causes of podocyte loss, has been reported to have a vital role in diabetic nephropathy (DN) pathogenesis, and understanding the mechanisms underlying the regulation of podocyte apoptosis is crucial. Metadherin (MTDH) is an important oncogene, which is overexpressed in most cancers and responsible for apoptosis, metastasis, and poor patient survival. Here we show that the expression levels of Mtdh and phosphorylated p38 mitogen-activated protein kinase (MAPK) are significantly increased, whereas those of the microRNA-30 family members (miR-30s) are considerably reduced in the glomeruli of DN rat model and in high glucose (HG)-induced conditionally immortalized mouse podocytes (MPC5)...
November 24, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27881924/rodent-models-of-diabetic-nephropathy-their-utility-and-limitations
#3
REVIEW
Munehiro Kitada, Yoshio Ogura, Daisuke Koya
Diabetic nephropathy is the most common cause of end-stage renal disease. Therefore, novel therapies for the suppression of diabetic nephropathy must be developed. Rodent models are useful for elucidating the pathogenesis of diseases and testing novel therapies, and many type 1 and type 2 diabetic rodent models have been established for the study of diabetes and diabetic complications. Streptozotocin (STZ)-induced diabetic animals are widely used as a model of type 1 diabetes. Akita diabetic mice that have an Ins2+/C96Y mutation and OVE26 mice that overexpress calmodulin in pancreatic β-cells serve as a genetic model of type 1 diabetes...
2016: International Journal of Nephrology and Renovascular Disease
https://www.readbyqxmd.com/read/27874055/the-coordinated-roles-of-mir-26a-and-mir-30c-in-regulating-tgf%C3%AE-1-induced-epithelial-to-mesenchymal-transition-in-diabetic-nephropathy
#4
Zongji Zheng, Meiping Guan, Yijie Jia, Dan Wang, Ruoyu Pang, Fuping Lv, Zhizhou Xiao, Ling Wang, Hongbin Zhang, Yaoming Xue
MicroRNAs (miRNAs) play vital roles in the development of diabetic nephropathy. Here, we compared the protective efficacies of miR-26a and miR-30c in renal tubular epithelial cells (NRK-52E) and determined whether they demonstrated additive effects in the attenuation of renal fibrosis. TGFβ1 suppressed miR-26a and miR-30c expression but up-regulated pro-fibrotic markers in NRK-52E cells, and these changes were also found in the kidney cortex of 40-week-old diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27834856/stearoyl-coa-desaturase-1-protects-cells-against-lipotoxicity-mediated-apoptosis-in-proximal-tubular-cells
#5
Tamaki Iwai, Shinji Kume, Masami Chin-Kanasaki, Shogo Kuwagata, Hisazumi Araki, Naoko Takeda, Takeshi Sugaya, Takashi Uzu, Hiroshi Maegawa, Shin-Ichi Araki
Saturated fatty acid (SFA)-related lipotoxicity is a pathogenesis of diabetes-related renal proximal tubular epithelial cell (PTEC) damage, closely associated with a progressive decline in renal function. This study was designed to identify a free fatty acid (FFA) metabolism-related enzyme that can protect PTECs from SFA-related lipotoxicity. Among several enzymes involved in FFA metabolism, we identified stearoyl-CoA desaturase-1 (SCD1), whose expression level significantly decreased in the kidneys of high-fat diet (HFD)-induced diabetic mice, compared with non-diabetic mice...
November 9, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27826011/roles-of-the-nlrp3-inflammasome-in-the-pathogenesis-of-diabetic-nephropathy
#6
REVIEW
Yuan-Ye Qiu, Li-Qin Tang
Diabetic nephropathy (DN) is a serious complication of diabetes mellitus, and persistent inflammation in circulatory and renal tissues is an important pathophysiological basis for DN. The essence of the microinflammatory state is the innate immune response, which is central to the occurrence and development of DN. Members of the inflammasome family, including both "receptors" and "regulators", are key to the inflammatory immune response. Nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) and other inflammasome components are able to detect endogenous danger signals, resulting in activation of caspase-1 as well as interleukin (IL)-1β, IL-18 and other cytokines; these events stimulate the inflammatory cascade reaction, which is crucial for DN...
November 5, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27825100/high-glucose-repatterns-human-podocyte-energy-metabolism-during-differentiation-and-diabetic-nephropathy
#7
Toshiyuki Imasawa, Emilie Obre, Nadège Bellance, Julie Lavie, Tomoko Imasawa, Claire Rigothier, Yahsou Delmas, Christian Combe, Didier Lacombe, Giovanni Benard, Stéphane Claverol, Marc Bonneu, Rodrigue Rossignol
Podocytes play a key role in diabetic nephropathy pathogenesis, but alteration of their metabolism remains unknown in human kidney. By using a conditionally differentiating human podocyte cell line, we addressed the functional and molecular changes in podocyte energetics during in vitro development or under high glucose conditions. In 5 mM glucose medium, we observed a stepwise activation of oxidative metabolism during cell differentiation that was characterized by peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α)-dependent stimulation of mitochondrial biogenesis and function, with concomitant reduction of the glycolytic enzyme content...
October 17, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27816946/advanced-glycation-end-products-mediated-cellular-and-molecular-events-in-the-pathology-of-diabetic-nephropathy
#8
Anil Kumar Pasupulati, P Swathi Chitra, G Bhanuprakash Reddy
Diabetic nephropathy (DN) is a major cause of morbidity and mortality in diabetic patients and a leading cause of end-stage renal disease (ESRD). Degenerative changes such as glomerular hypertrophy, hyperfiltration, widening of basement membranes, tubulointerstitial fibrosis, glomerulosclerosis and podocytopathy manifest in various degrees of proteinuria in DN. One of the key mechanisms implicated in the pathogenesis of DN is non-enzymatic glycation (NEG). NEG is the irreversible attachment of reducing sugars onto free amino groups of proteins by a series of events, which include the formation of Schiff's base and an Amadori product to yield advanced glycation end products (AGEs)...
December 1, 2016: Biomolecular Concepts
https://www.readbyqxmd.com/read/27799462/sodium-butyrate-activates-nrf2-to-ameliorate-diabetic-nephropathy-possibly-via-inhibition-of-hdac
#9
Wenpeng Dong, Ye Jia, Xiuxia Liu, Huan Zhang, Tie Li, Wenlin Huang, Xudong Chen, Fuchun Wang, Weixia Sun, Hao Wu
Oxidative stress contributes to the pathogenesis of diabetic nephropathy (DN). Nuclear factor erythroid 2-related factor 2 (NRF2) plays a key role in cellular defense against oxidative stress. NRF2 activators have shown promising preventive effects on DN. Sodium butyrate (NaB) is a known activator of NRF2. However, it is unknown whether NRF2 is required for NaB protection against DN. Therefore, streptozotocin-induced diabetic C57BL/6 Nrf2 knockout and their wild-type mice were treated in the presence or absence of NaB for 20 weeks...
January 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/27798458/the-angiotensin-type-2-receptor-and-the-kidney
#10
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/27773814/role-of-sirtuin3-in-high-glucose-induced-apoptosis-in-renal-tubular-epithelial-cells
#11
Xiaocui Jiao, Ying Li, Tao Zhang, Maodong Liu, Yanqing Chi
The apoptosis of renal tubular epithelial cells contributes to the pathogenesis of diabetic nephropathy. High glucose-induced mitochondrial oxidative stress is considered to be an important mediator for renal tubular cell apoptosis. Sirtuin3(Sirt3), a kind of mitochondria-localized nicotinamide adenine dinucleotide(NAD(+))-dependent protein deacetylase, has been reported to regulate the generation of ROS in mitochondria through regulating acetylation level and activity of several key mitochondrial enzymes. In this study, we investigated the role of Sirt3 on high glucose-induced apoptosis in HK-2 cells...
October 20, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27770539/inhibiting-microrna-503-and-microrna-181d-with-losartan-ameliorates-diabetic-nephropathy-in-kkay-mice
#12
XinWang Zhu, CongXiao Zhang, QiuLing Fan, XiaoDan Liu, Gang Yang, Yi Jiang, LiNing Wang
BACKGROUND Diabetic nephropathy (DN) is the most lethal diabetic microvascular complication; it is a major cause of renal failure, and an increasingly globally prominent healthcare problem. MATERIAL AND METHODS To identify susceptible microRNAs for the pathogenesis of DN and the targets of losartan treatment, microRNA arrays were employed to survey the glomerular microRNA expression profiles of KKAy mice treated with or without losartan. KKAy mice were assigned to either a losartan-treated group or a non-treatment group, with C57BL/6 mice used as a normal control...
October 22, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27765534/diabetic-nephropathy-and-endothelial-dysfunction-current-and-future-therapies-and-emerging-of-vascular-imaging-for-preclinical-renal-kinetic-study
#13
REVIEW
Wilson Kc Leung, L Gao, Parco M Siu, Christopher Wk Lai
An explosion in global epidemic of type 2 diabetes mellitus poses major rise in cases with vascular endothelial dysfunction ranging from micro- (retinopathy, nephropathy and neuropathy) to macro-vascular (atherosclerosis and cardiomyopathy) conditions. Functional destruction of endothelium is regarded as an early event that lays the groundwork for the development of renal microangiopathy and subsequent clinical manifestation of nephropathic symptoms. Recent research has shed some light on the molecular mechanisms of type 2 diabetes-associated comorbidity of endothelial dysfunction and nephropathy...
December 1, 2016: Life Sciences
https://www.readbyqxmd.com/read/27754167/sy-12-3-are-ras-inhibitors-necessary-for-all-patients-with-diabetes-and-chronic-kidney-disease
#14
Shokei Kim-Mitsuyama
There is accumulating evidence that RAS inhibitors not only reduce blood pressure, but also exert pleiotropic effects, including a renoprotective effect, amelioration of insulin resistance, reduction in onset of diabetes, and suppression of cardiovascular remodelling,. However, the definite benefit of RAS inhibition in treatment of hypertension with CKD or DM is not conclusive. We previously performed the OlmeSartan and Calcium Antagonists Randomized (OSCAR) study comparing the preventive effect of high-dose ARB therapy versus ARB plus CCB combination therapy on cardiovascular morbidity and mortality in 1164 Japanese elderly hypertensive patients with baseline type 2 diabetes and/or CVD (Am J Med (2012))...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27752226/diabetes-mellitus-and-oxidative-stress-a-concise-review
#15
Ullah Asmat, Khan Abad, Khan Ismail
Human body is continuously exposed to different types of agents that results in the production of reactive species called as free radicals (ROS/RNS) which by the transfer of their free unpaired electron causes the oxidation of cellular machinery. In order to encounter the deleterious effects of such species, body has got endogenous antioxidant systems or it obtains exogenous antioxidants from diet that neutralizes such species and keeps the homeostasis of body. Any imbalance between the RS and antioxidants leads to produce a condition known as "oxidative stress" that results in the development of pathological condition among which one is diabetes...
September 2016: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/27742196/cathepsins-are-potential-therapeutic-targets-in-kidney%C3%A2-disease
#16
Santhosh Kumar Vr, Hans-Joachim Anders
Cathepsins are a class of proteases with diverse biological activities inside and, in part, also outside cells. Recent studies suggest that cathepsins are involved in the pathogenesis of diabetic nephropathy and in disease activity of autoimmune immune complex glomerulonephritis. Targeting specific cathepsins with suitable antagonists may hold promises for therapeutic interventions.
November 2016: Kidney International
https://www.readbyqxmd.com/read/27733370/protease-activated-receptors-in-kidney-disease-progression
#17
REVIEW
Oleg Palygin, Daria V Ilatovskaya, Alexander Staruschenko
Protease-activated receptors (PARs) are members of a well-known family of transmembrane G protein-coupled receptors (GPCRs). Four PARs have been identified to date, of which PAR1 and PAR2 are the most abundant receptors, and have been shown to be expressed in the kidney vascular and tubular cells. PAR signaling is mediated by an N-terminus tethered ligand that can be unmasked by serine protease cleavage. The receptors are activated by endogenous serine proteases, such as thrombin (acts on PARs 1, 3, and 4) and trypsin (PAR2)...
December 1, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27706190/influence-of-different-levels-of-lipoic-acid-synthase-gene-expression-on-diabetic-nephropathy
#18
Longquan Xu, Sylvia Hiller, Stephen Simington, Volker Nickeleit, Nobuyo Maeda, Leighton R James, Xianwen Yi
Oxidative stress is implicated in the pathogenesis of diabetic nephropathy (DN) but outcomes of many clinical trials are controversial. To define the role of antioxidants in kidney protection during the development of diabetic nephropathy, we have generated a novel genetic antioxidant mouse model with over- or under-expression of lipoic acid synthase gene (Lias). These models have been mated with Ins2Akita/+ mice, a type I diabetic mouse model. We compare the major pathologic changes and oxidative stress status in two new strains of the mice with controls...
2016: PloS One
https://www.readbyqxmd.com/read/27703550/serum-interleukin-18-and-its-gene-haplotypes-profile-as-predictors-in-patients-with-diabetic-nephropathy
#19
Ahmed I Abd Elneam, Nahla M Mansour, Nayel A Zaki, Mohamed A Taher
BACKGROUND: Diabetic nephropathy (DN) is known as an acute microvascular complexity as a subsequence progression in diabetes mellitus type 1 and 2. Many evidence pointed that the proinflammatory cytokine Interleukin (IL)-18 might be involved in the pathogenesis of DN. AIM: The current study aimed to evaluate the association of serum IL-18 and its promoter gene polymorphisms with diabetic nephropathy. METHODS: This study included 62 diabetic nephropathy patients (DN group) compared to 52 diabetes mellitus patients (DM group)...
September 15, 2016: Open Access Macedonian Journal of Medical Sciences
https://www.readbyqxmd.com/read/27696561/evaluation-of-the-relationship-between-microalbuminuria-and-urine-ischemia-modified-albumin-levels-in-patients-with-diabetic-nephropathy
#20
Mustafa Bilgi, Ahmet Keser, Huseyin Katlandur, Emel Sahin, Ali Osman Kalkan, Murat Yildiz, Aysel Kiyici, Mustafa Keles
INTRODUCTION: Ischemia-modified albumin (IMA) is a marker which can be associated with oxidative stress in various ischemic and non-ischemic processes. Oxidative stress plays roles in diabetes mellitus, its complications and pathogenesis. Serum IMA levels are examined in various clinical events. However, urine IMA levels have not yet been evaluated in diabetic patients. In this study, we aim to examine the relationship between metabolic features and urine microalbuminuria levels of diabetic patients and their urine IMA levels...
October 1, 2016: Journal of Clinical Laboratory Analysis
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