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Diabetic nephropathy pathological pathways

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https://www.readbyqxmd.com/read/28633927/dencichine-ameliorates-kidney-injury-in-induced-type-ii-diabetic-nephropathy-via-the-tgf-%C3%AE-smad-signalling-pathway
#1
Li Jie, Qiu Pengcheng, He Qiaoyan, Bi Linlin, Zhang Meng, Wang Fang, Jia Min, Yan Li, Zhang Ya, Yang Qian, Wang Siwang
Diabetic nephropathy (DN), a common complication associated with both type I and type II diabetes mellitus (DM), is a major cause of chronic nephropathy and a common cause of end-stage renal diseases (ESRD) throughout the world. This study is aimed to determine whether dencichine (De) can ameliorate renal damage in high-glucose-and-fat diet combined STZ (streptozocin) induced DN in type II DM rats and to investigate the potential underlying mechanisms. Markers of metabolism, diabetes, and renal function, and levels of extracellular matrix (ECM) collagen I (Col I), collagen IV (Col IV), fibronectin (FN) and laminin (LN), and of proteins in the TGF-β/Smad pathway were analysed through RT-PCR, western blot, immunofluorescence and immunohistochemistry...
June 17, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28529539/jiangtang-decoction-ameliorate-diabetic-nephropathy-through-the-regulation-of-pi3k-akt-mediated-nf-%C3%AE%C2%BAb-pathways-in-kk-ay-mice
#2
Jin-Ni Hong, Wei-Wei Li, Lin-Lin Wang, Hao Guo, Yong Jiang, Yun-Jia Gao, Peng-Fei Tu, Xue-Mei Wang
BACKGROUND: Jiangtang decoction (JTD) is a China patented drug which contains Euphorbia humifusa Willd, Salvia miltiorrhiza Bunge, Astragalus mongholicus Bunge, Anemarrhena asphodeloides Bunge, and Coptis chinensis Franch. For decades, it has also been used clinically to treat diabetic nephropathy (DN) effectively; however, the associated mechanisms remain unknown. Thus, the present study aimed to examine the protective efficacy of JTD in DN and elucidate the underlying molecular mechanisms...
2017: Chinese Medicine
https://www.readbyqxmd.com/read/28436957/pyruvate-kinase-m2-activation-may-protect-against-the-progression-of-diabetic-glomerular-pathology-and-mitochondrial-dysfunction
#3
Weier Qi, Hillary A Keenan, Qian Li, Atsushi Ishikado, Aimo Kannt, Thorsten Sadowski, Mark A Yorek, I-Hsien Wu, Samuel Lockhart, Lawrence J Coppey, Anja Pfenninger, Chong Wee Liew, Guifen Qiang, Alison M Burkart, Stephanie Hastings, David Pober, Christopher Cahill, Monika A Niewczas, William J Israelsen, Liane Tinsley, Isaac E Stillman, Peter S Amenta, Edward P Feener, Matthew G Vander Heiden, Robert C Stanton, George L King
Diabetic nephropathy (DN) is a major cause of end-stage renal disease, and therapeutic options for preventing its progression are limited. To identify novel therapeutic strategies, we studied protective factors for DN using proteomics on glomeruli from individuals with extreme duration of diabetes (ł50 years) without DN and those with histologic signs of DN. Enzymes in the glycolytic, sorbitol, methylglyoxal and mitochondrial pathways were elevated in individuals without DN. In particular, pyruvate kinase M2 (PKM2) expression and activity were upregulated...
June 2017: Nature Medicine
https://www.readbyqxmd.com/read/28408805/effect-of-berberine-on-the-renal-tubular-epithelial-to-mesenchymal-transition-by-inhibition-of-the-notch-snail-pathway-in-diabetic-nephropathy-model-kkay-mice
#4
Guannan Yang, Zongjiang Zhao, Xinxue Zhang, Amin Wu, Yawei Huang, Yonghui Miao, Meijuan Yang
Renal tubular epithelial-to-mesenchymal transition (EMT) and renal tubular interstitial fibrosis are the main pathological changes of diabetic nephropathy (DN), which is a common cause of end-stage renal disease. Previous studies have suggested that berberine (BBR) has antifibrotic effects in the kidney and can reduce apoptosis and inhibit the EMT of podocytes in DN. However, the effect of BBR on the renal tubular EMT in DN and its mechanisms of action are unknown. This study was performed to explore the effects of BBR on the renal tubular EMT and the molecular mechanisms of BBR in DN model KKAy mice and on the high glucose (HG)-induced EMT in mouse renal tubular epithelial cells...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28237649/protein-kinase-ck2%C3%AE-catalytic-subunit-ameliorates-diabetic-renal-inflammatory-fibrosis-via-nf-%C3%AE%C2%BAb-signaling-pathway
#5
Junying Huang, Zhiquan Chen, Jie Li, Qiuhong Chen, Jingyan Li, Wenyan Gong, Jiani Huang, Peiqing Liu, Heqing Huang
Activation of casein kinase 2 (CK2) is closely linked to the body disturbance of carbohydrate metabolism and inflammatory reaction. The renal chronic inflammatory reaction in the setting of diabetes is one of the important hallmarks of diabetic renal fibrosis. However, it remains unknown whether CK2 influences the process of diabetic renal fibrosis. The current study is aimed to investigate if CK2α ameliorates renal inflammatory fibrosis in diabetes via NF-κB pathway. To explore potential regulatory mechanism of CK2α, the expression and activity of CK2α, which were studied by plasmid transfection, selective inhibitor, small-interfering RNA (siRNA) and adenovirus infection in vitro or in vivo, were analyzed by means of western blotting (WB), dual luciferase reporter assay and electrophoretic mobility shift assay (EMSA)...
May 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28183033/diabetic-nephropathy-a-potential-savior-with-rotten-egg-smell
#6
REVIEW
George J Dugbartey
Diabetic nephropathy (DN) is currently the leading cause of end-stage renal disease. Despite optimal management, DN is still a major contributor to morbidity and mortality of diabetic patients worldwide. The major pathological alterations in DN include excessive accumulation and deposition of extracellular matrix, leading to expansion of mesangial matrix, thickening of glomerular basement membrane and tubulointerstitial fibrosis. At the molecular level, accumulating evidence suggests that hyperglycemia or high glucose mediates renal injury in DN via multiple molecular mechanisms such as induction of oxidative stress, upregulation of renal transforming growth factor beta-1 expression, production of proinflammatory cytokines, activation of fibroblasts and renin angiotensin system, and depletion of adenosine triphosphate...
April 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28123638/nicousamide-protects-kidney-podocyte-by-inhibiting-the-tgf%C3%AE-receptor-ii-phosphorylation-and-age-rage-signaling
#7
Sen Zhang, Dongjie Wang, Nina Xue, Fangfang Lai, Ming Ji, Jing Jin, Xiaoguang Chen
Nicousamide, a clinical phase II renal protective new drug, has been demonstrated to have renal protective effect on diabetic nephropathy (DN) by experimental animal model. Its known molecular mechanisms include AGE formation blocking and moderately decreasing the blood pressure. Nicousamide shows potential on attenuating albuminuria, thereby suggests it might have protective effect on podocytes. The aim of present study was to investigate whether nicousamide could protect integrity of podocytes, and further its protection mechanisms...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28118981/monitoring-p53-by-mdm2-and-mdmx-is-required-for-endocrine-pancreas-development-and-function-in-a-spatio-temporal-manner
#8
Yiwei Zhang, Shelya X Zeng, Qian Hao, Hua Lu
Although p53 is not essential for normal embryonic development, it plays a pivotal role in many biological and pathological processes, including cell fate determination-dependent and independent events and diseases. The expression and activity of p53 largely depend on its two biological inhibitors, MDM2 and MDMX, which have been shown to form a complex in order to tightly control p53 to an undetectable level during early stages of embryonic development. However, more delicate studies using conditional gene-modification mouse models show that MDM2 and MDMX may function separately or synergistically on p53 regulation during later stages of embryonic development and adulthood in a cell and tissue-specific manner...
March 1, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28099346/liuwei-dihuang-pill-treats-diabetic-nephropathy-in-rats-by-inhibiting-of-tgf-%C3%AE-smads-mapk-and-nf-kb-and-upregulating-expression-of-cytoglobin-in-renal-tissues
#9
Zhong Ju Xu, Shi Shu, Zhi Jie Li, Yu Min Liu, Rui Yi Zhang, Yue Zhang
Liuwei Dihuang pill (LDP) was assessed for its effects on renal deficiency.90 STZ induced DN rats were divided into groups (n = 22) without treatment (STZ) and LDP treated (STZ-L) (n = 23), Zhenwu decoction treated (STZ-Z) (n = 22), and valsartan treated (STZ-V) (n = 23) groups, with 16 normal control rats. Total urine protein (TP), blood urea nitrogen (BUN), and serum creatinine (Cr) were measured. Superoxide dismutase (SOD), nitric oxide synthase (NOS), and malondialdehyde (MDA) concentrations as well as expression/phosphorylation of SMAD3, SMAD2, and α-SMA, TGF-β, RI /II, P38, ERK, and NF-kB in renal tissues were determined...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28049280/new-therapeutic-agents-in-diabetic-nephropathy
#10
REVIEW
Yaeni Kim, Cheol Whee Park
Studies investigating diabetic nephropathy (DN) have mostly focused on interpreting the pathologic molecular mechanisms of DN, which may provide valuable tools for early diagnosis and prevention of disease onset and progression. Currently, there are few therapeutic drugs for DN, which mainly consist of antihypertensive and antiproteinuric measures that arise from strict renin-angiotensin-aldosterone system inactivation. However, these traditional therapies are suboptimal and there is a clear, unmet need for treatments that offer effective schemes beyond glucose control...
January 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28017719/repression-of-mir-217-protects-against-high-glucose-induced-podocyte-injury-and-insulin-resistance-by-restoring-pten-mediated-autophagy-pathway
#11
Juan Sun, Zhao Pin Li, Rui Qin Zhang, Hui Min Zhang
Podocyte damage is the initial hallmark of diabetic nephropathy (DN), leading to the increasing morbidity and mortality in diabetic patients. Recent researches have corroborated the critical roles of miRNAs in the pathological progression of DN. Here, elevation of miR-217 was verified in high glucose (HG)-stimulated podocytes. Moreover, blocking miR-217 expression antagonized HG-induced cell injury by attenuating the adverse role of HG on cell viability and inhibiting ROS levels and cell apoptosis. Simultaneously, miR-217 repression restored HG-disrupted insulin resistance by elevating glucose uptake and nephrin expression, an essential component for insulin-induced glucose uptake...
January 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27942176/identification-of-urinary-proteins-potentially-associated-with-diabetic-kidney-disease
#12
R K Marikanty, M K Gupta, S V B Cherukuvada, S S S Kompella, A K Prayaga, S Konda, R V Polisetty, M M Idris, P V Rao, G R Chandak, K V Dakshinamurty
Diabetic nephropathy (DN) is the most common cause of chronic kidney disease. Although several parameters are used to evaluate renal damage, in many instances, there is no pathological change until damage is already advanced. Mass spectrometry-based proteomics is a novel tool to identify newer diagnostic markers. To identify urinary proteins associated with renal complications in diabetes, we collected urine samples from 10 type 2 diabetes patients each with normoalbuminuria, micro- and macro-albuminuria and compared their urinary proteome with that of 10 healthy individuals...
November 2016: Indian Journal of Nephrology
https://www.readbyqxmd.com/read/27849555/role-of-post-transcriptional-regulation-of-mrna-stability-in-renal-pathophysiology-focus-on-chronic-kidney-disease
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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...
September 13, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27627216/nephroprotective-effects-of-metformin-in-diabetic-nephropathy
#19
REVIEW
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...
April 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27585918/astragaloside-iv-ameliorates-renal-injury-in-db-db-mice
#20
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
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