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Diabetic nephropathy pathological pathways

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https://www.readbyqxmd.com/read/27849555/role-of-post-transcriptional-regulation-of-mrna-stability-in-renal-pathophysiology-focus-on-chronic-kidney-disease
#1
REVIEW
Eva Feigerlová, Shyue-Fang Battaglia-Hsu
Chronic kidney disease (CKD) represents an important public health problem. Its progression to end-stage renal disease is associated with increased morbidity and mortality. The determinants of renal function decline are not fully understood. Recent progress in the understanding of post-transcriptional regulation of mRNA stability has helped the identification of both the trans- and cis-acting elements of mRNA as potential markers and therapeutic targets for difficult-to-diagnose and -treat diseases, including CKDs such as diabetic nephropathy...
November 14, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27803669/the-role-of-hydrogen-sulfide-in-renal-system
#2
REVIEW
Xu Cao, Jin-Song Bian
Hydrogen sulfide has gained recognition as the third gaseous signaling molecule after nitric oxide and carbon monoxide. This review surveys the emerging role of H2S in mammalian renal system, with emphasis on both renal physiology and diseases. H2S is produced redundantly by four pathways in kidney, indicating the abundance of this gaseous molecule in the organ. In physiological conditions, H2S was found to regulate the excretory function of the kidney possibly by the inhibitory effect on sodium transporters on renal tubular cells...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27706238/involvement-of-the-nlrc4-inflammasome-in-diabetic-nephropathy
#3
Fang Yuan, Ryan Kolb, Gaurav Pandey, Wei Li, Lin Sun, Fuyou Liu, Fayyaz S Sutterwala, Yinghong Liu, Weizhou Zhang
Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease worldwide but current treatments remain suboptimal. The role of inflammation in DN has only recently been recognized. It has been shown that the NLRP3-inflammasome contributes to DN development by inducing interleukin (IL)-1β processing and secretion. In an effort to understand other IL-1β activating mechanism during DN development, we examined the role of the NLRC4-inflammasome in DN and found that NLRC4 is a parallel mechanism, in addition to the NLRP3-inflammasome, to induce pro-IL-1β processing and activation...
2016: PloS One
https://www.readbyqxmd.com/read/27684203/how-to-study-basement-membrane-stiffness-as-a-biophysical-trigger-in-prostate-cancer-and-other-age-related-pathologies-or-metabolic-diseases
#4
Mercedes Rodriguez-Teja, Claudia Breit, Mitchell Clarke, Kamil Talar, Kai Wang, Mohammad A Mohammad, Sage Pickwell, Guillermina Etchandy, Graeme J Stasiuk, Justin Sturge
Here we describe a protocol that can be used to study the biophysical microenvironment related to increased thickness and stiffness of the basement membrane (BM) during age-related pathologies and metabolic disorders (e.g. cancer, diabetes, microvascular disease, retinopathy, nephropathy and neuropathy). The premise of the model is non-enzymatic crosslinking of reconstituted BM (rBM) matrix by treatment with glycolaldehyde (GLA) to promote advanced glycation endproduct (AGE) generation via the Maillard reaction...
September 20, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27649495/renoprotective-effects-of-atorvastatin-in-diabetic-mice-downregulation-of-rhoa-and-upregulation-of-akt-gsk3
#5
Thiago Bruder-Nascimento, Glaucia Callera, Augusto Cesar Montezano, Tayze T Antunes, Ying He, Aurelie Nguyen Dinh Cat, Nathanne S Ferreira, Pedro A Barreto, Vânia C Olivon, Rita C Tostes, Rhian M Touyz
Potential benefits of statins in the treatment of chronic kidney disease beyond lipid-lowering effects have been described. However, molecular mechanisms involved in renoprotective actions of statins have not been fully elucidated. We questioned whether statins influence development of diabetic nephropathy through reactive oxygen species, RhoA and Akt/GSK3 pathway, known to be important in renal pathology. Diabetic mice (db/db) and their control counterparts (db/+) were treated with atorvastatin (10 mg/Kg/day, p...
2016: PloS One
https://www.readbyqxmd.com/read/27649140/renal-protective-effects-of-low-molecular-weight-of-inonotus-obliquus-polysaccharide-liop-on-hfd-stz-induced-nephropathy-in-mice
#6
Yen-Jung Chou, Wei-Chih Kan, Chieh-Min Chang, Yi-Jen Peng, Hsien-Yi Wang, Wen-Chun Yu, Yu-Hsuan Cheng, Yu-Rou Jhang, Hsia-Wei Liu, Jiunn-Jye Chuu
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease in diabetes mellitus. Oxidative stress, insulin resistance and pro-inflammatory cytokines have been shown to play an important role in pathogeneses of renal damage on type 2 diabetes mellitus (DM). Inonotus obliquus (IO) is a white rot fungus that belongs to the family Hymenochaetaceae; it has been used as an edible mushroom and exhibits many biological activities including anti-tumor, anti-oxidant, anti-inflammatory and anti-hyperglycemic properties...
2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27627216/nephroprotective-effects-of-metformin-in-diabetic-nephropathy
#7
Sreenithya Ravindran, Vinitha Kuruvilla, Kerry Wilbur, Shankar Munusamy
Metformin, a well-known anti-diabetic agent, is very effective in lowering blood glucose in patients with type 2 diabetes with minimal side-effects. Metformin is also being recommended in the treatment of obesity and polycystic ovary syndrome. Metformin elicits its therapeutic effects mainly via activation of AMP-activated kinase (AMPK) pathway. Renal cells under hyperglycemic or proteinuric conditions exhibit inactivation of cell defense mechanisms such as AMPK and autophagy, and activation of pathologic pathways such as mammalian target of rapamycin (mTOR), endoplasmic reticulum (ER) stress, epithelial-to-mesenchymal transition (EMT), oxidative stress, and hypoxia...
September 14, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27585918/astragaloside-iv-ameliorates-renal-injury-in-db-db-mice
#8
Huili Sun, Wenjing Wang, Pengxun Han, Mumin Shao, Gaofeng Song, Heng Du, Tiegang Yi, Shunmin Li
Diabetic nephropathy is a lethal complication of diabetes mellitus and a major type of chronic kidney disease. Dysregulation of the Akt pathway and its downstream cascades, including mTOR, NFκB, and Erk1/2, play a critical role in the development of diabetic nephropathy. Astragaloside IV is a major component of Huangqi and exerts renal protection in a mouse model of type 1 diabetes. The current study was undertaken to investigate the protective effects of diet supplementation of AS-IV on renal injury in db/db mice, a type 2 diabetic mouse model...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27582102/re-thinking-glomerular-basement-membrane-thickening-in-diabetic-nephropathy-adaptive-or-pathogenic
#9
Caroline B Marshall
Diabetic nephropathy (DN) is the leading cause of chronic kidney disease in the United States and is a major cause of cardiovascular disease and death. DN develops insidiously over a span of years before clinical manifestations, including microalbuminuria and declining glomerular filtration rate (GFR), are evident. During the clinically silent period, structural lesions develop, including glomerular basement membrane (GBM) thickening, mesangial expansion, and glomerulosclerosis. Once microalbuminuria is clinically apparent, structural lesions are often considerably advanced and GFR decline may then proceed rapidly toward end-stage kidney disease...
August 31, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27571993/notoginsenoside-r1-ameliorates-podocyte-injury-in-rats-with-diabetic-nephropathy-by-activating-the-pi3k-akt-signaling-pathway
#10
Guodong Huang, Jianzhen Lv, Tongyu Li, Guoli Huai, Xiang Li, Shaowei Xiang, Longlong Wang, Zhenlin Qin, Jianli Pang, Bingyu Zou, Yi Wang
The present study was designed to examine the protective effect of notoginsenoside R1 (NR1) on podocytes in a rat model of streptozotocin (STZ)‑induced diabetic nephropathy (DN), and to explore the mechanism responsible for NR1-induced renal protection. Diabetes was induced by a single injection of STZ, and NR1 was administered daily at a dose of 5 mg/kg (low dose), 10 mg/kg (medium) and 20 mg/kg (high) for 16 weeks in Sprague-Dawley rats. Blood glucose levels, body weight and proteinuria were measured every 4 weeks, starting on the day that the rats received NR1...
October 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27521287/geniposide-reduces-development-of-streptozotocin-induced-diabetic-nephropathy-via-regulating-nf-%C3%AE%C2%BAb-signaling-pathways
#11
Xiaolei Hu, Xiaomei Zhang, Guoxi Jin, Zhaoming Shi, Weihua Sun, Fengling Chen
Renal pathology was a commonly seen complication in patients with diabetes. Geniposide (GPO) was previously demonstrated to modulate glucose metabolism in diabetes. This study was to investigate effects of GPO in streptozotocin (STZ) induced diabetic rats and its underlying mechanism. Renal function in diabetic rats was evaluated by levels of serum creatinine (Scr), blood urea nitrogen (BUN) and urinary albumin. Renal inflammation was appraised by inflammatory cells infiltration and pro-inflammatory cytokines production...
August 13, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27488452/resveratrol-inhibits-renal-interstitial-fibrosis-in-diabetic-nephropathy-by-regulating-ampk-nox4-ros-pathway
#12
Ting He, Jiachuan Xiong, Ling Nie, Yanlin Yu, Xu Guan, Xinli Xu, Tangli Xiao, Ke Yang, Liang Liu, Daohai Zhang, Yunjian Huang, Jingbo Zhang, Junping Wang, Kumar Sharma, Jinghong Zhao
: Renal interstitial fibrosis is a major pathologic feature of diabetic nephropathy, while the pathogenesis and therapeutic interventions of diabetic renal interstitial fibrosis are not well established. In this study, we first demonstrated that high glucose could induce renal fibroblast (NRK-49F) cell proliferation and activation to myofibroblasts, accompanied by a significant increase in the intracellular levels of reactive oxygen species (ROS) derived from nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4)...
August 4, 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/27379538/gonadectomy-prevents-the-increase-in-blood-pressure-and-glomerular-injury-in-angiotensin-converting-enzyme-2-knockout-diabetic-male-mice-effects-on-renin-angiotensin-system
#13
Sergi Clotet, María José Soler, Marta Rebull, Javier Gimeno, Susan B Gurley, Julio Pascual, Marta Riera
BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) deletion worsens kidney injury, and its amplification ameliorates diabetic nephropathy. Male sex increases the incidence, prevalence, and progression of chronic kidney disease in our environment. METHOD: Here, we studied the effect of ACE2 deficiency and gonadectomy (GDX) on diabetic nephropathy and its relationship with fibrosis, protein kinase B (Akt) activation, and the expression of several components of the renin-angiotensin system (RAS)...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27317945/tgr5-activation-suppressed-s1p-s1p2-signaling-and-resisted-high-glucose-induced-fibrosis-in-glomerular-mesangial-cells
#14
Zhiying Yang, Fengxiao Xiong, Yu Wang, Wenyan Gong, Junying Huang, Cheng Chen, Peiqing Liu, Heqing Huang
Glucose and lipid metabolism disorders and chronic inflammation in the kidney tissues are largely responsible for causative pathological mechanism of renal fibrosis in diabetic nephropathy (DN). As our previous findings confirmed that, sphingosine 1-phosphate (S1P)/sphingosine 1-phosphate receptor 2 (S1P2) signaling activation promoted renal fibrosis in diabetes. Numerous studies have demonstrated that the G protein-coupled bile acid receptor TGR5 exhibits effective regulation of glucose and lipid metabolism and anti-inflammatory effects...
September 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27292312/berberine-attenuates-high-glucose-induced-fibrosis-by-activating-the-g-protein-coupled-bile-acid-receptor-tgr5-and-repressing-the-s1p2-mapk-signaling-pathway-in-glomerular-mesangial-cells
#15
Zhiying Yang, Jie Li, Fengxiao Xiong, Junying Huang, Cheng Chen, Peiqing Liu, Heqing Huang
Berberine (BBR) exerts powerful renoprotective effects on diabetic nephropathy (DN), but the underlying mechanisms remain unclear. We previously demonstrated that activation of the G protein-coupled bile acid receptor TGR5 ameliorates diabetic nephropathy by inhibiting the activation of the sphingosine 1-phosphate (S1P)/sphingosine 1-phosphate receptor 2 (S1P2) signaling pathway. In this study, we explored the role of TGR5 in the BBR-induced downregulation of sphingosine 1-phosphate receptor 2 (S1P2)/mitogen-activated protein kinase (MAPK)-mediated fibrosis in glomerular mesangial cells (GMCs)...
August 15, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27252593/a-comprehensive-review-on-the-genetic-regulation-of-cisplatin-induced-nephrotoxicity
#16
Zeneida Herrera-Pérez, Norbert Gretz, Harsh Dweep
Cisplatin (CDDP) is a well-known antineoplastic drug which has been extensively utilized over the last decades in the treatment of numerous kinds of tumors. However, CDDP induces a wide range of toxicities in a dose-dependent manner, among which nephrotoxicity is of particular importance. Still, the mechanism of CDDP-induced renal damage is not completely understood; moreover, the knowledge about the role of microRNAs (miRNAs) in the nephrotoxic response is still unknown. miRNAs are known to interact with the representative members of a diverse range of regulatory pathways (including postnatal development, proliferation, inflammation and fibrosis) and pathological conditions, including kidney diseases: polycystic kidney diseases (PKDs), diabetic nephropathy (DN), kidney cancer, and drug-induced kidney injury...
June 2016: Current Genomics
https://www.readbyqxmd.com/read/27212945/the-protective-effect-of-beraprost-sodium-on-diabetic-nephropathy-by-inhibiting-inflammation-and-p38-mapk-signaling-pathway-in-high-fat-diet-streptozotocin-induced-diabetic-rats
#17
Li Peng, Jie Li, Yixing Xu, Yangtian Wang, Hong Du, Jiaqing Shao, Zhimin Liu
Background. p38 mitogen-activated protein kinase (MAPK) plays a crucial role in regulating signaling pathways implicated in inflammatory processes leading to diabetic nephropathy (DN). This study aimed to examine p38 MAPK activation in DN and determine whether beraprost sodium (BPS) ameliorates DN by inhibiting inflammation and p38 MAPK signaling pathway in diabetic rats. Methods. Forty male Sprague Dawley (SD) rats were randomly divided into the normal control group, type 2 diabetic group, and BPS treatment group...
2016: International Journal of Endocrinology
https://www.readbyqxmd.com/read/27186267/early-protective-role-of-mst1-knockdown-in-response-to-experimental-diabetic-nephropathy
#18
Weihua Wu, Maoping Zhang, Santao Ou, Xing Liu, Ling Xue, Jian Liu, Yuke Wu, Ying Li, Qi Liu
Diabetic nephropathy (DN) is a progressive kidney disease caused by the damage of capillaries in kidney's glomeruli. Mammalian Sterile 20-like kinase 1 (MST1) has been reported to play an important role in many disease, such as diabetes, cardiac disease and ect. However, the potential role of MST1 pathway in DN has not been fully evaluated. In this study, we hypothesized that MST1 could be involved in DN, and MST1 knockdown would attenuate the DN injury in experimental diabetic nephropathy induced by streptozotocin (STZ)...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27055155/abatacept-treatment-does-not-preserve-renal-function-in-the-streptozocin-induced-model-of-diabetic-nephropathy
#19
Jenny Norlin, Lisbeth Nielsen Fink, Peter Helding Kvist, Elisabeth Douglas Galsgaard, Ken Coppieters
Diabetic nephropathy (DN) is one of the most severe complications of diabetes and remains the largest cause of end-stage renal disease in the Western world. Treatment options are limited and novel therapies that effectively slow disease progression are warranted. Previous work suggested that treatment with CTLA4-Ig (abatacept), a molecule that binds and blocks B7-1 and is licensed for the treatment of rheumatoid arthritis, could ameliorate DN. This study was designed to assess whether B7-1 signalling constitutes a promising therapeutic pathway for DN...
2016: PloS One
https://www.readbyqxmd.com/read/27032892/role-of-ragulator-in-the-regulation-of-mechanistic-target-of-rapamycin-signaling-in-podocytes-and-glomerular-function
#20
Yao Yao, Junying Wang, Sei Yoshida, Shigeyuki Nada, Masato Okada, Ken Inoki
Aberrant activation of mechanistic target of rapamycin complex 1 (mTORC1) in glomerular podocytes leads to glomerular insufficiency and may contribute to the development of glomerular diseases, including diabetic nephropathy. Thus, an approach for preventing mTORC1 activation may allow circumvention of the onset and progression of mTORC1-dependent podocyte injury and glomerular diseases. mTORC1 activation requires inputs from both growth factors and nutrients that inactivate the tuberous sclerosis complex (TSC), a key suppressor of mTORC1, on the lysosome...
December 2016: Journal of the American Society of Nephrology: JASN
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