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Inflammation diabetic nephropathy

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https://www.readbyqxmd.com/read/28341121/activation-of-epha1-epha-receptor-axis-attenuates-diabetic-nephropathy-in-mice
#1
Yihui Li, Hongdan Yan, Feng Wang, Shanying Huang, Yun Zhang, Zhihao Wang, Ming Zhong, Wei Zhang
The Eph family of receptor tyrosine kinases serves as key modulators of various cellular functions, including inflammation, hypertrophy and fibrosis. Recent analyses have revealed that a member of the Eph family, EphA1, plays a pivotal role in regulating insulin metabolism and kidney injury. However, the importance of EphA1 in diabetic nephropathy has not been recognized. We established a diabetic nephropathy mouse model using a high-fat diet and streptozotocin (STZ) injection. Then, the recombinant adeno-associated virus type 9 (AAV9) overexpressing EphA1 or a negative control was injected locally into the kidney...
March 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28325753/mouse-model-for-inherited-renal-fibrosis-associated-with-endoplasmic-reticulum-stress
#2
Sian E Piret, Eric Olinger, Anita A C Reed, M Andrew Nesbit, Tertius A Hough, Liz Bentley, Olivier Devuyst, Roger Cox, Rajesh V Thakker
Renal fibrosis is a common feature of renal failure resulting from multiple aetiologies, including diabetic nephropathy, hypertension and inherited renal disorders. However, the mechanisms of renal fibrosis are incompletely understood and we therefore explored these by establishing a mouse model for a renal tubular disorder, referred to as autosomal dominant tubulointerstitial kidney disease (ADTKD) due to missense uromodulin (UMOD) mutations (ADTKD-UMOD). ADTKD-UMOD, which is associated with retention of mutant uromodulin in the endoplasmic reticulum (ER) of renal thick ascending limb cells, is characterized by hyperuricemia, interstitial fibrosis, inflammation, and renal failure, and we used targeted homologous recombination to generate a knock-in mouse model with an ADTKD-causing missense cysteine to arginine uromodulin mutation (C125R)...
March 21, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28323921/emerging-roles-for-micrornas-in-diabetic-microvascular-disease-novel-targets-for-therapy
#3
Yu Zhang, Xinghui Sun, Basak Icli, Mark W Feinberg
Chronic, low-grade systemic inflammation and impaired microvascular function are critical hallmarks in the development of insulin resistance. Accordingly, insulin resistance is a major risk factor for type 2 diabetes and cardiovascular disease. Accumulating studies demonstrate that restoration of impaired function of the diabetic macro- and microvasculature may ameliorate a range of cardiovascular disease states and diabetes-associated complications. In this review, we focus on the emerging role of microRNAs, non-coding RNAs that fine-tune target gene expression and signaling pathways, in insulin-responsive tissues and cell types important for maintaining optimal vascular homeostasis and preventing the sequelae of diabetes-induced end organ injury...
February 17, 2017: Endocrine Reviews
https://www.readbyqxmd.com/read/28294194/phosphodiesterase-5-inhibition-preserves-renal-hemodynamics-and-function-in-mice-with-diabetic-kidney-disease-by-modulating-mir-22-and-bmp7
#4
Riccardo Pofi, Daniela Fiore, Rita De Gaetano, Giuseppe Panio, Daniele Gianfrilli, Carlotta Pozza, Federica Barbagallo, Yang Kevin Xiang, Konstantinos Giannakakis, Susanna Morano, Andrea Lenzi, Fabio Naro, Andrea M Isidori, Mary Anna Venneri
Diabetic Nephropathy (DN) is the leading cause of end-stage renal disease. Preclinical and experimental studies show that PDE5 inhibitors (PDE5is) exert protective effects in DN improving perivascular inflammation. Using a mouse model of diabetic kidney injury we investigated the protective proprieties of PDE5is on renal hemodynamics and the molecular mechanisms involved. PDE5i treatment prevented the development of DN-related hypertension (P < 0.001), the increase of urine albumin creatinine ratio (P < 0...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28291548/the-role-of-interleukin-17a-in-the-pathogenesis-of-kidney-diseases
#5
REVIEW
Charlotte Cortvrindt, Reinhart Speeckaert, Alena Moerman, Joris R Delanghe, Marijn M Speeckaert
Being a member of the IL-17 family, comprising six structurally related ligands, IL-17A is a cytokine, produced by multiple cell types, such as CD4(+)αβ T cells, γδ T cells, natural killer cells, neutrophils, macrophages, dendritic cells, lymphoid tissue inducer cells, mast cells and plasma cells. IL-17A participates in tissue inflammation by inducing the expression of chemokines, proinflammatory cytokines and matrix metalloproteases. Besides its role in host defence against infectious diseases, IL-17A is involved in different autoimmune and inflammatory diseases...
March 10, 2017: Pathology
https://www.readbyqxmd.com/read/28272773/comparative-rna-seq-transcriptome-analyses-reveal-distinct-metabolic-pathways-in-diabetic-nerve-and-kidney-disease
#6
Lucy M Hinder, Meeyoung Park, Amy E Rumora, Junguk Hur, Felix Eichinger, Subramaniam Pennathur, Matthias Kretzler, Frank C Brosius, Eva L Feldman
Treating insulin resistance with pioglitazone normalizes renal function and improves small nerve fibre function and architecture; however, it does not affect large myelinated nerve fibre function in mouse models of type 2 diabetes (T2DM), indicating that pioglitazone affects the body in a tissue-specific manner. To identify distinct molecular pathways regulating diabetic peripheral neuropathy (DPN) and nephropathy (DN), as well those affected by pioglitazone, we assessed DPN and DN gene transcript expression in control and diabetic mice with or without pioglitazone treatment...
March 8, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28271466/intestinal-microbiota-in-type-2-diabetes-and-chronic-kidney-disease
#7
REVIEW
Alice Sabatino, Giuseppe Regolisti, Carmela Cosola, Loreto Gesualdo, Enrico Fiaccadori
PURPOSE OF THE REVIEW: Diabetes mellitus is a major cause of kidney disease [chronic kidney disease (CKD) and end-stage renal disease (ESRD)] and are both characterized by an increased risk of cardiovascular events. Diabetes and kidney disease are also commonly associated with a chronic inflammatory state, which is now considered a non-traditional risk factor for atherosclerosis. In the case of type 2 diabetes mellitus (T2DM), inflammation is mainly a consequence of visceral obesity, while in the case of CKD or ESRD patients on dialysis, inflammation is caused by multiple factors, classically grouped as dialysis-related and non-dialysis-related...
March 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28246295/autophagy-inhibits-the-accumulation-of-advanced-glycation-end-products-by-promoting-lysosomal-biogenesis-and-function-in-the-kidney-proximal-tubules
#8
Atsushi Takahashi, Yoshitsugu Takabatake, Tomonori Kimura, Ikuko Maejima, Tomoko Namba, Takeshi Yamamoto, Jun Matsuda, Satoshi Minami, Jun-Ya Kaimori, Isao Matsui, Taiji Matsusaka, Fumio Niimura, Tamotsu Yoshimori, Yoshitaka Isaka
Advanced glycation end products (AGEs) are involved in the progression of diabetic nephropathy. AGEs filtered by glomeruli or delivered from the circulation are endocytosed and degraded in the lysosomes of kidney proximal tubular epithelial cells (PTECs). Autophagy is a highly conserved degradation system which regulates intracellular homeostasis by engulfing cytoplasmic components. We have recently demonstrated that autophagic degradation of damaged lysosomes is indispensable for cellular homeostasis in some settings...
February 28, 2017: Diabetes
https://www.readbyqxmd.com/read/28240316/p53-induces-mir199a-3p-to-suppress-socs7-for-stat3-activation-and-renal-fibrosis-in-uuo
#9
Ruhao Yang, Xuan Xu, Huiling Li, Jinwen Chen, Xudong Xiang, Zheng Dong, Dongshan Zhang
The role of p53 in renal fibrosis has recently been suggested, however, its function remains controversial and the underlying mechanism is unclear. Here, we show that pharmacological and genetic blockade of p53 attenuated renal interstitial fibrosis, apoptosis, and inflammation in mice with unilateral urethral obstruction (UUO). Interestingly, p53 blockade was associated with the suppression of miR-215-5p, miR-199a-5p&3p, and STAT3. In cultured human kidney tubular epithelial cells (HK-2), TGF-β1 treatment induced fibrotic changes, including collagen I and vimentin expression, being associated with p53 accumulation, p53 Ser15 phosphorylation, and miR-199a-3p expression...
February 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28224182/parp-inhibition-ameliorates-nephropathy-in-an-animal-model-of-type-2-diabetes-focus-on-oxidative-stress-inflammation-and-fibrosis
#10
Esraa M Zakaria, Nabila N El-Maraghy, Ahmed F Ahmed, Abdelmonim A Ali, Hany M El-Bassossy
Poly(ADP-ribose) polymerase (PARP) enzyme contributes to nephropathy, a serious diabetic complication which may lead to end-stage renal disease. The study aims to investigate the effect of PARP over-activation on kidney functions in a type 2 diabetic rat model. The study also tests the therapeutic use of PARP inhibitors in diabetic nephropathy. Type 2 diabetes was induced in adult male rats by high-fructose/high-fat diet and low streptozotocin dose. Then, the PARP inhibitor 4-aminobenzamide (4-AB) was administered daily for 10 weeks...
February 21, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28215166/seaweed-polysaccharides-new-therapeutic-insights-against-the-inflammatory-response-in-diabetic-nephropathy
#11
Vaishnu Devi Da, Pragasam Viswanathan
BACKGROUND: The higher risk of diabetic nephropathy (DN) leads to end stage renal diseases in worldwide, which is associated with chronic inflammation. Currently, the available treatments are limited, lack of efficacy and safety. Therefore, we are in need of novel targets and advanced treatments to reduce the necessity for the renal replacement therapy and burden of this disease management. In this review, we performed through an inflammatory mechanism that contribute to DN, will provide a key point to the finding off novel therapeutic agents...
February 16, 2017: Anti-inflammatory & Anti-allergy Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28196866/sglt2-expression-is-increased-in-human-diabetic-nephropathy-sglt2-inhibition-decreases-renal-lipid-accumulation-inflammation-and-the-development-of-nephropathy-in-diabetic-mice
#12
Xiaoxin X Wang, Jonathan Levi, Yuhuan Luo, Komuraiah Myakala, Michal Herman-Edelstein, Liru Qiu, Dong Wang, Yingqiong Peng, Almut Grenz, Scott Lucia, Evgenia Dobrinskikh, Vivette D D'Agati, Hermann Koepsell, Jeffrey B Kopp, Avi Rosenberg, Moshe Levi
There is very limited human renal sodium gradient dependent glucose transporter protein SGLT2 mRNA and protein expression data reported in the literature. Aim 1 of this study was to determine SGLT2 mRNA and protein levels in human and animal models of diabetic nephropathy. We have found that the expression of SGLT2 mRNA and protein is increased in renal biopsies from human subjects with diabetic nephropathy. This is in contrast to db-db mice which had no changes in renal SGLT-2 protein expression. Furthermore, the effect of SGLT2 inhibition on renal lipid content and inflammation is not known...
February 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28182703/nephropathy-in-pparg-null-mice-highlights-ppar%C3%AE-systemic-activities-in-metabolism-and-in-the-immune-system
#13
Barbara Toffoli, Federica Gilardi, Carine Winkler, Magnus Soderberg, Laura Kowalczuk, Yvan Arsenijevic, Krister Bamberg, Olivier Bonny, Béatrice Desvergne
Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-dependent transcription factor involved in many aspects of metabolism, immune response, and development. Total-body deletion of the two Pparg alleles provoked generalized lipoatrophy along with severe type 2 diabetes. Herein, we explore the appearance and development of structural and functional alterations of the kidney, comparing Pparg null-mice to their littermate controls (carrying Pparg floxed alleles). We show that renal hypertrophy and functional alterations with increased glucosuria and albuminuria are already present in 3 weeks-old Pparg null-mice...
2017: PloS One
https://www.readbyqxmd.com/read/28182085/maresin-1-mitigates-high-glucose-induced-mouse-glomerular-mesangial-cell-injury-by-inhibiting-inflammation-and-fibrosis
#14
Shi Tang, Chenlin Gao, Yang Long, Wei Huang, Jiao Chen, Fang Fan, Chunxia Jiang, Yong Xu
Background. Inflammation and fibrosis are the important pathophysiologic processes in diabetic nephropathy (DN). Maresin 1 is a potential anti-inflammatory lipid mediator, which has displayed powerful proresolving activities. Aim. We determine whether maresin 1 has protective effect on mouse glomerular mesangial cells (GMCs) induced by high glucose. Methods. We cultured GMCs stimulated by high glucose and categorized as follows: normal glucose group (5.6 mmol/L), high glucose group (30 mmol/L), mannitol group, maresin 1 intervention group (1, 10, and 100 nmol/L), maresin 1 and normal glucose group, and the N-acetylcysteine (NAC) intervention group (10 μmol/L NAC)...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28163536/hypertension-influences-the-exponential-progression-of-inflammation-and-oxidative-stress-in-streptozotocin-induced-diabetic-kidney
#15
Rupadevi Muthaian, Rajaa Muthu Pakirisamy, Subramani Parasuraman, Ramasamy Raveendran
OBJECTIVE: To investigate the association of hypertension coexisting with diabetes mellitus with oxidative stress and inflammation in the kidneys of streptozotocin (STZ)-induced diabetic rats. MATERIALS AND METHODS: Male Wistar rats were used for the experiments. Blood glucose (BG), urea, blood pressure (BP), and heart rate (HR) were analyzed before and 48 h after STZ injection. Further, these parameters were monitored up to 3 months of diabetes induction. Subsequently, the inflammatory markers (C-reactive protein, tumor necrosis factor-alpha, and nitrate) and oxidative stress markers were estimated after 3 months of diabetes induction in the kidney homogenate...
October 2016: Journal of Pharmacology & Pharmacotherapeutics
https://www.readbyqxmd.com/read/28162229/the-increased-transforming-growth-factor-%C3%AE-signaling-induced-by-diabetes-protects-retinal-vessels
#16
Zeina Dagher, Chiara Gerhardinger, Joseph Vaz, Michael Goodridge, Francesco Tecilazich, Mara Lorenzi
The roles of transforming growth factor (TGF)-β in extracellular matrix production and vascular remodeling, coupled with increased TGF-β expression and signaling in diabetes, suggest TGF-β as an important contributor to the microangiopathy of diabetic retinopathy and nephropathy. To investigate whether increased TGF-β signaling could be a therapeutic target for preventing retinopathy, we used a pharmacologic approach (SM16, a selective inhibitor of the type 1 TGF-β receptor activin receptor-like kinase 5, orally active) to inhibit the increased, but not the basal, Tgf-β signaling in retinal vessels of diabetic rats...
February 1, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28159781/insights-into-diabetic-kidney-disease-using-urinary-proteomics-and-bioinformatics
#17
Julie A D Van, James W Scholey, Ana Konvalinka
A number of proteomic and peptidomic analyses of urine from diabetic subjects have been published in the quest for a biomarker that predicts progression of nephropathy. Less attention has been paid to the relationships between urinary proteins and the underlying biological processes revealed by the analyses. In this review, we focus on the biological processes identified by studying urinary proteins and protein-protein interactions at each stage of diabetic nephropathy to provide an overview of the events underlying progression of kidney disease reflected in the urine...
February 3, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28151474/lincrna-gm4419-knockdown-ameliorates-nf-%C3%AE%C2%BAb-nlrp3-inflammasome-mediated-inflammation-in-diabetic-nephropathy
#18
Hong Yi, Rui Peng, Lu-Yu Zhang, Yan Sun, Hui-Min Peng, Han-Deng Liu, Li-Juan Yu, Ai-Ling Li, Ya-Juan Zhang, Wen-Hao Jiang, Zheng Zhang
Diabetic nephropathy (DN) as the primary cause of end-stage kidney disease is a common complication of diabetes. Recent researches have shown the activation of nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) and NACHT, LRR and PYD domain-containing protein 3 (NLRP3) inflammasome are associated with inflammation in the progression of DN, but the exact mechanism is unclear. Long noncoding RNAs (lncRNAs) have roles in the development of many diseases including DN. However, the relationship between lncRNAs and inflammation in DN remains largely unknown...
February 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28135651/baicalin-and-chrysin-mixture-imparts-cyto-protection-against-methylglyoxal-induced-cytotoxicity-and-diabetic-tubular-injury-by-modulating-rage-oxidative-stress-and-inflammation
#19
Jyotsna Singh, Bhushan P Chaudhari, Poonam Kakkar
Protective effect of mixture of flavonoids baicalin and chrysin (BCH) was studied against methylglyoxal (MG, a precursor of AGEs) induced cytotoxicity in NRK 52E kidney epithelial cells. Flow cytometry and microscopic analysis showed increased ROS generation, compromised antioxidant status, depolarization of mitochondria and apoptosis in MG stressed cells which were significantly transformed (p≤0.01) during BCH co-treatment. In vivo studies in streptozotocin induced diabetic rats increased protein levels of iNOS, protein kinase C (PKC) and decreased IκB which was modulated by oral BCH treatment (75mg baicalin and 10mg chrysin/kg b...
March 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28121358/ablation-of-carbohydrate-responsive-element-binding-protein-improves-kidney-injury-in-streptozotocin-induced-diabetic-mice
#20
W Zhang, X Li, S-G Zhou
OBJECTIVE: Carbohydrate-responsive element-binding protein (ChREBP) has been reported to regulate glucose and lipids metabolism in the liver. However, its role in the complicated pathophysiology of diabetic nephropathy is not understood. MATERIALS AND METHODS: C57BL/6 mice treated with streptozotocin (STZ) or vehicle control to induce diabetic models. The mRNA and protein levels of ChREBP in kidneys of control and diabetic mice were determined by real-time PCR or Western Blot, respectively...
January 2017: European Review for Medical and Pharmacological Sciences
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