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Diabetic nephropathy pathological pathways

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https://www.readbyqxmd.com/read/29033543/effect-of-echinacoside-on-kidney-fibrosis-by-inhibition-of-tgf-%C3%AE-1-smads-signaling-pathway-in-the-db-db-mice-model-of-diabetic-nephropathy
#1
Fengjuan Tang, Yarong Hao, Xue Zhang, Jian Qin
Kidney fibrosis and renal tubular epithelial-to-mesenchymal transition (EMT) are the main pathological changes of diabetic nephropathy (DN), which eventually leads to end-stage renal disease. Previous studies have suggested that echinacoside (ECH) is antifibrotic in the liver. However, the effect of ECH on kidney fibrosis in DN and its mechanisms are unknown. This study was performed to explore the effect of ECH on kidney fibrosis and also the molecular mechanisms of ECH in a db/db mice model of DN. Our results showed that, relative to db/db mice, the mice in the ECH group had an improved general state and reduced blood glucose and 24-hour urinary protein levels...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28986066/the-crosstalk-between-sirt1-and-keap1-nrf2-are-anti-oxidative-pathway-forms-a-positive-feedback-loop-to-inhibit-fn-and-tgf-%C3%AE-1-expressions-in-rat-glomerular-mesangial-cells
#2
Kaipeng Huang, Xiang Gao, Wentao Wei
Oxidative stress aroused by advanced glycation-end products (AGEs) is a culprit in the pathological progression of diabetic nephropathy. Both Sirt1 and the Keap1/Nrf2/ARE anti-oxidative pathway exert crucial inhibitory effects on the development of diabetic nephropathy. Our previous study has confirmed that Sirt1 activation can inhibit the upregulation of fibronectin (FN) and transforming growth factor-β1 (TGF-β1) by promoting Keap1/Nrf2/ARE pathway in glomerular mesangial cells (GMCs) challenged with AGEs...
October 3, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28974087/the-pathological-role-of-the-ubiquitination-pathway-in-diabetic-nephropathy
#3
Paola Pontrelli, Annarita Oranger, Mariagrazia Barozzino, Francesca Conserva, Massimo Papale, Loreto Gesualdo
Diabetic nephropathy (DN) is a chronic complication of type 2 diabetes and is the most frequent form of chronic kidney disease that can lead to end-stage renal disease. Different pathways, involved in oxidative stress, inflammation, fibrosis and cell death, are responsible for the pathogenesis of DN and regulate the progression of the disease. Ubiquitination is a fundamental pathway in intracellular signaling whose role is emerging in the regulation of molecular processes responsible for several human diseases...
October 3, 2017: Minerva Medica
https://www.readbyqxmd.com/read/28956186/diabetic-nephropathy-a-tangled-web-to-unweave
#4
REVIEW
Corey Magee, David J Grieve, Chris J Watson, Derek P Brazil
Diabetic nephropathy (DN) is currently the leading cause of end-stage renal disease globally. Given the increasing incidence of diabetes, many experts hold the view that DN will eventually progress toward pandemic proportions. Whilst hyperglycaemia-induced vascular dysfunction is the primary initiating mechanism in DN, its progression is also driven by a heterogeneous set of pathological mechanisms, including oxidative stress, inflammation and fibrosis. Current treatment strategies for DN are targeted against the fundamental dysregulation of glycaemia and hypertension...
September 27, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28925940/zebrafish-as-a-model-for-the-study-of-microvascular-complications-of-diabetes-and-their-mechanisms
#5
REVIEW
Karl Heckler, Jens Kroll
Diabetes mellitus (DM) is a crucial metabolic disease that leads to severe disorders. These include macrovascular complications such as myocardial infarction, stroke, and peripheral artery disease and microvascular complications including diabetic nephropathy, neuropathy, and retinopathy. Diabetes mellitus, along with its associated organ pathologies, is one of the key problems in today's medicine. Zebrafish is an upcoming disease model organism in diabetes research. Its glucose metabolism and the pathways of reactive metabolite formation are very similar to those of humans...
September 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28904427/micrornas-involvement-in-renal-pathophysiology-a-bird-s-eye-view
#6
REVIEW
P Jaswani, S Prakash, A Dhar, R K Sharma, N Prasad, S Agrawal
MicroRNAs (miRNAs) are known to suppress gene expression by binding to messenger RNAs and in turn regulate different pathophysiological processes. Transforming growth factor-β, mitogen-activated protein kinase signaling, and Wnt signaling-like major pathways associated with miRNAs are involved with kidney diseases. The discovery of miRNAs has provided new insights into kidney pathologies and may provide effective therapeutic strategies. Research has demonstrated the role of miRNAs in a variety of kidney diseases including diabetic nephropathy, lupus nephritis, hypertension, nephritic syndrome, acute kidney injury, renal cell carcinoma, and renal fibrosis...
September 2017: Indian Journal of Nephrology
https://www.readbyqxmd.com/read/28793292/huangqi-decoction-ameliorates-streptozotocin-induced-rat-diabetic-nephropathy-through-antioxidant-and-regulation-of-the-tgf-%C3%AE-mapk-ppar-%C3%AE-signaling
#7
Haiyan Han, Aili Cao, Li Wang, Hengjiang Guo, Yingjun Zang, Zezheng Li, Xuemei Zhang, Wen Peng
BACKGROUND/AIMS: Huangqi Decoction (HQD) has been traditionally used to treat diabetes mellitus in China. The present study was carried out to assess the protective effect of HQD on diabetic nephropathy (DN) using the streptozotocin-induced (STZ) diabetic rats. METHODS: Diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg) in male Wistar rats. 40 diabetic rats were divided into 5 groups: vehicle-treated (DN group), 0.45, 0.15, 0.05 g/kg HQD-treated diabetic group (HQD group) and 1 mg/kg rosiglitazone-treated diabetic group (RGZ group)...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28791309/research-progress-on-mechanism-of-podocyte-depletion-in-diabetic-nephropathy
#8
REVIEW
Haoran Dai, Qingquan Liu, Baoli Liu
Diabetic nephropathy (DN) together with glomerular hyperfiltration has been implicated in the development of diabetic microangiopathy in the initial stage of diabetic diseases. Increased amounts of urinary protein in DN may be associated with functional and morphological alterations of podocyte, mainly including podocyte hypertrophy, epithelial-mesenchymal transdifferentiation (EMT), podocyte detachment, and podocyte apoptosis. Accumulating studies have revealed that disruption in multiple renal signaling pathways had been critical in the progression of these pathological damages, such as adenosine monophosphate-activated kinase signaling pathways (AMPK), wnt/β-catenin signaling pathways, endoplasmic reticulum stress-related signaling pathways, mammalian target of rapamycin (mTOR)/autophagy pathway, and Rho GTPases...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28769803/lovastatin-alleviates-endothelial-to-mesenchymal-transition-in-glomeruli-via-suppression-of-oxidative-stress-and-tgf-%C3%AE-1-signaling
#9
Zejun Ma, Lili Zhu, Yan Liu, Zhida Wang, Yang Yang, Liming Chen, Qiulun Lu
Statins may decrease chronic kidney diseases (CKDs) risk, but their underlying molecular mechanisms are not completely understood. Recent studies indicate Endothelial-to-mesenchymal transition (EndMT) plays an important role contributing to renal interstitial fibrosis. In the present study, we first investigated whether lovastatin could ameliorate renal fibrosis via suppression of EndMT and its possible mechanism. In vitro experiments, lovastatin significantly ameliorated microalbuminuria and pathologic changes in diabetic rats...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28701517/mesangial-cell-mammalian-target-of-rapamycin-complex-1-activation-results-in-mesangial-expansion
#10
Kojiro Nagai, Tatsuya Tominaga, Sayo Ueda, Eriko Shibata, Masanori Tamaki, Motokazu Matsuura, Seiji Kishi, Taichi Murakami, Tatsumi Moriya, Hideharu Abe, Toshio Doi
Human glomerular diseases can be caused by several different diseases, many of which include mesangial expansion and/or proliferation followed by glomerulosclerosis. However, molecular mechanisms underlying the pathologic mesangial changes remain poorly understood. Here, we investigated the role of the mammalian target of rapamycin complex 1 (mTORC1)-S6 kinase pathway in mesangial expansion and/or proliferation by ablating an upstream negative regulator, tuberous sclerosis complex 1 (TSC1), using tamoxifen-induced Foxd1-Cre mice [Foxd1ER(+) TSC1 mice]...
October 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28700904/inhibition-of-high-glucose-induced-inflammation-and-fibrosis-by-a-novel-curcumin-derivative-prevents-renal-and-heart-injury-in-diabetic-mice
#11
Hongjin Chen, Xi Yang, Kongqin Lu, Chun Lu, Yunjie Zhao, Suqing Zheng, Jieli Li, Zhangjian Huang, Yi Huang, Yali Zhang, Guang Liang
Hyperglycemia-induced inflammation and fibrosis have important roles in the pathogenesis of diabetic nephropathy and cardiomyopathy. With inflammatory cytokines and signaling pathways as important mediators, targeting inflammation may be an effective approach to new avenue for treating diabetic complications. J17, a molecule with structural similarities to curcumin, exhibited good anti-inflammatory activities by inhibiting LPS-induced inflammatory response in macrophages. However, its ability to alleviate hyperglycemia-induced injury via its anti-inflammatory actions remained unclear...
August 15, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28670380/serum-levels-of-wnt1-inducible-signaling-pathway-protein-1-wisp-1-a-noninvasive-biomarker-of-renal-fibrosis-in-subjects-with-chronic-kidney-disease
#12
Xiang Zhong, Yue Ju Tu, Yi Li, Ping Zhang, Wei Wang, Sha Sha Chen, Li Li, Arthur Ck Chung, Hui Yao Lan, Hai Yong Chen, Gui Sen Li, Li Wang
WNT1-inducible signaling pathway protein-1 (WISP-1) is an extracellular matrix-related protein that plays multiple roles in cellular physiology and pathology. Accumulating evidence shows that WISP-1 is involved in the process underlying fibrotic diseases. However, the correlation between WISP-1 and renal fibrosis is unknown. In this study, we hypothesized that WISP-1 levels might be correlated with renal fibrosis and could be used as a noninvasive biomarker to screen for renal fibrosis in patients with chronic kidney disease (CKD)...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28664547/vitamin-d3-ameliorates-podocyte-injury-through-the-nephrin-signalling-pathway
#13
Ourania Trohatou, Effie-Fotini Tsilibary, Aristidis Charonis, Christos Iatrou, Garyfalia Drossopoulou
Renal podocytes form the main filtration barrier possessing unique phenotype maintained by proteins including podocalyxin and nephrin, which are modulated in pathological conditions. In diabetic nephropathy (DN), podocytes become structurally and functionally compromised. Nephrin, a structural backbone protein of the slit diaphragm, acts as regulator of podocyte intracellular signalling with renoprotective role. Vitamin D3 through its receptor, VDR, provides renal protection in DN but limited data exist about its effect on podocytes...
October 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28633927/dencichine-ameliorates-kidney-injury-in-induced-type-ii-diabetic-nephropathy-via-the-tgf-%C3%AE-smad-signalling-pathway
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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