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Pathogenesis diabetic nephropathy

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https://www.readbyqxmd.com/read/28428931/the-role-of-renal-proximal-tubule-transport-in-the-regulation-of-blood-pressure
#1
REVIEW
Shoko Horita, Motonobu Nakamura, Masashi Suzuki, Nobuhiko Satoh, Atsushi Suzuki, Yukio Homma, Masaomi Nangaku
The electrogenic sodium/bicarbonate cotransporter 1 (NBCe1) on the basolateral side of the renal proximal tubule plays a pivotal role in systemic acid-base homeostasis. Mutations in the gene encoding NBCe1 cause severe proximal renal tubular acidosis accompanied by other extrarenal symptoms. The proximal tubule reabsorbs most of the sodium filtered in the glomerulus, contributing to the regulation of plasma volume and blood pressure. NBCe1 and other sodium transporters in the proximal tubule are regulated by hormones, such as angiotensin II and insulin...
March 2017: Kidney Research and Clinical Practice
https://www.readbyqxmd.com/read/28401169/epigenetic-regulations-in-diabetic-nephropathy
#2
REVIEW
Zeyuan Lu, Na Liu, Feng Wang
Diabetic nephropathy (DN) is a chronic complication of diabetes and the most common cause of end-stage kidney disease. It has been reported that multiple factors are involved in the pathogenesis of DN, while the molecular mechanisms that lead to DN are still not fully understood. Numerous risk factors for the development of diabetic nephropathy have been proposed, including ethnicity and inherited genetic differences. Recently, with the development of high-throughput technologies, there is emerging evidence that suggests the important role of epigenetic mechanisms in the pathogenesis of DN...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28393693/update-on-the-protective-renal-effects-of-metformin-in-diabetic-nephropathy
#3
Andreas Eisenreich, Ulrike Leppert
BACKGROUND: Diabetic nephropathy is one of the most important complications in patients with diabetes mellitus. Main steps crucial for the pathogenesis of diabetic nephropathy involve amongst others the modulation of cell signaling via AMP-activated kinase (AMPK) and mammalian target of rapamycin (mTOR), reactive oxygen generation, and endoplasmic reticulum stress under diabetic or hyperglycemic conditions. These processes mediate increased loss of renal cells, such as podocytes, which consequentially leads to renal damage and loss of renal functions, such as structural integrity and glomerular filtration in diabetic nephropathy...
April 4, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28387811/dual-therapy-targeting-the-endocannabinoid-system-prevents-experimental-diabetic-nephropathy
#4
Federica Barutta, Serena Grimaldi, Roberto Gambino, Kiran Vemuri, Alexandros Makriyannis, Laura Annaratone, Vincenzo di Marzo, Graziella Bruno, Gabriella Gruden
Background.: The endocannabinoid system has been implicated in the pathogenesis of diabetic nephropathy (DN). We investigated the effect of combined therapy with AM6545, a 'peripherally' restricted cannabinoid receptor type 1 (CB1R) neutral antagonist, and AM1241, a cannabinoid receptor type 2 (CB2R) agonist, in experimental DN. Methods.: Renal function and structure, podocyte proteins and markers of both fibrosis and inflammation were studied in streptozotocin-induced diabetic mice treated for 14 weeks with vehicle, AM6545, AM1241 and AM6545-AM1241...
April 6, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28367814/-autophagy-in-the-kidney
#5
Nicolas Pallet
Autophagy is a highly conserved, physiological, catabolic process, involving the lysosomal degradation of cytosolic components, including macromolecules (such as proteins and lipids) and cytosolic organelles. Autophagy is believed to be essential for the maintenance of cellular homeostasis, for a number of fundamental biological activities, and an important component of the complex response of cells to multiple forms of stress. Autophagy is involved in the pathogenesis of a number of clinically important disorders but, until recently, little was known about its connection to kidney diseases...
March 2017: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/28363842/potential-of-angiotensin-ii-receptor-blockers-in-the-treatment-of-diabetic-retinopathy
#6
REVIEW
Tapan Behl, Anita Kotwani
Impairments in renin-angiotensin-aldosterone system during diabetes mellitus, leading to its dysfunction, have been known since a decade. Hyperglycemia induces several pathological alterations which upregulate this system, accounting for overexpression of its downstream signaling molecules, amongst which angiotensin II (Ang II) and aldosterone hold prime pathological notoriety. Although it is well known that elevated plasma levels of Ang II play a crucial role in the pathophysiology of type-II diabetic mellitus, by inducing and aggravating insulin resistance, it is not quite much known that it equally elevates the possibility/risk of development of diabetic complications...
May 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/28363724/hidden-targets-of-ubiquitin-proteasome-system-to-prevent-diabetic-nephropathy
#7
REVIEW
Santosh Kumar Goru, Almesh Kadakol, Anil Bhanudas Gaikwad
Diabetic nephropathy (DN) is the major cause of end stage renal failure. Although, several therapeutic targets have emerged to prevent the progression of DN, the number of people with DN still continues to rise worldwide, suggesting an urgent need of novel targets to prevent DN completely. Currently, the role of ubiquitin proteasome system (UPS) has been highlighted in the pathogenesis and progression of various diseases like obesity, insulin resistance, atherosclerosis, cancers, neurodegerative disorders and including secondary complications of diabetes...
March 29, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28363692/il-6-signaling-in-diabetic-nephropathy-from-pathophysiology-to-therapeutic-perspectives
#8
Eva Feigerlová, Shyue-Fang Battaglia-Hsu
Diabetic nephropathy (DN) is a leading cause of chronic kidney disease (CKD). Interleukin-6 (IL-6) signaling participates in inflammation responses central to the progression of DN. Current evidence suggests that these IL-6 responses are mediated via gp130-STAT3 dependent mechanisms which, on one hand, trigger globally the transition from innate to adaptive immune response, and on the other hand act locally for tissue remodeling and immune cell infiltration. In diabetic conditions the role of IL-6 is not well elucidated...
March 23, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28360429/interleukin-20-targets-podocytes-and-is-upregulated-in-experimental-murine-diabetic-nephropathy
#9
Yu-Hsiang Hsu, Hsing-Hui Li, Junne-Ming Sung, Wei-Yu Chen, Ya-Chin Hou, Yun-Han Weng, Wei-Ting Lai, Chih-Hsing Wu, Ming-Shi Chang
Interleukin (IL)-20, a proinflammatory cytokine of the IL-10 family, is involved in acute and chronic renal failure. The aim of this study was to elucidate the role of IL-20 during diabetic nephropathy development. We found that IL-20 and its receptor IL-20R1 were upregulated in the kidneys of mice and rats with STZ-induced diabetes. In vitro, IL-20 induced MMP-9, MCP-1, TGF-β1 and VEGF expression in podocytes. IL-20 was upregulated by hydrogen peroxide, high-dose glucose and TGF-β1. In addition, IL-20 induced apoptosis in podocytes by activating caspase-8...
March 31, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28356293/urinary-dcr2-is-a-novel-biomarker-for-tubulointerstitial-injury-in-patients-with-diabetic-nephropathy
#10
Jia Chen, Wei-Wei Zhang, Ke-Hong Chen, Li-Rong Lin, Huan-Zi Dai, Kai-Long Li, Jian-Guo Zhang, Lu-Quan Zheng, Bi-Qiong Fu, Ya-Ni He
Tubulointerstitial injury (TII) plays a crucial role in the progression of diabetic nephropathy (DN), but lack of specific and sensitive biomarkers for monitoring TII in DN management. This study is to investigate whether urinary decoy receptor 2 (uDcR2) could serve as a novel noninvasive biomarker for assessing TII in DN. We recruited 311 type 2 diabetics and 139 DN patients which diagnosed by renal biopsy. uDcR2 levels were measured by ELISA and renal DcR2 expression was detected immunohistochemically. Associations between uDcR2 and renal DcR2, renal functional parameters were evaluated...
March 29, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28352321/toll-like-receptor-2-agonist-exacerbates-renal-injury-in-diabetic-mice
#11
Fanglin Li, Ningyu Zhang, Zhiming Li, Lihua Deng, Jianjie Zhang, Yunfeng Zhou
Inflammation is implicated in the pathogenesis of diabetic nephropathy (DN). Toll-like receptor 2 (TLR2) is a ligand-activated membrane-bound receptor, which induces an inflammatory response, thus serving a crucial role in the pathogenesis of DN. The present study aimed to determine whether a TLR2 agonist, Pam3CysSK4, modulates the development of DN. A mouse model of DN was induced using streptozotocin (STZ) and, following the confirmation of hyperglycemia, mice were treated with or without Pam3CysSK4. Pathological and functional markers, including the activation of nuclear factor (NF)-κB, expression of TLR2, inflammatory infiltration, myeloid differentiation primary response gene 88 and monocyte chemoattractant protein-1 were assessed...
February 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28336553/tlr2-knockout-protects-against-diabetes-mediated-changes-in-cerebral-perfusion-and-cognitive-deficits
#12
Trevor Hardigan, Caterina Hernandez, Rebecca Ward, M Nasrul Hoda, Adviye Ergul
The risk of cognitive decline in diabetes (Type 1 and Type 2) is significantly greater compared to normoglycemic patients, and the risk of developing dementia in diabetic patients is doubled. The etiology for this is likely multifactorial, but one mechanism that has gained increasing attention is decreased cerebral perfusion as a result of cerebrovascular dysfunction. The innate immune system has been shown to play a role in diabetic vascular complications, notably through Toll-like receptor (TLR) stimulated release of pro-inflammatory cytokines and chemokines that leads to vascular damage...
February 22, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28319415/transforming-growth-factor-beta-1-an-important-biomarker-for-developing-cardiovascular-diseases-in-chronic-renal-failure
#13
E Avci, G Alp Avci, B Ozcelik, S Coskun Cevher, M Suicmez
OBJECTIVE: Our study focuses on the determination and evaluation of TGF-β1 levels of patients receiving hemodialysis treatment because of chronic renal failure. BACKGROUND: Chronic renal failure, characterized by irreversible loss of renal function, is a major public health problem in the world. Transforming growth factor-beta is a multifunctional cytokine involved in the cellular growth, differentiation, migration, apoptosis and immune regulation. Among the three TGF-β isoforms, TGF-β1 plays a key role in the pathogenesis of renal diseases...
2017: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/28291548/the-role-of-interleukin-17a-in-the-pathogenesis-of-kidney-diseases
#14
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...
April 2017: Pathology
https://www.readbyqxmd.com/read/28289043/exocytosis-mediated-urinary-full-length-megalin-excretion-is-linked-with-the-pathogenesis-of-diabetic-nephropathy
#15
Shankhajit De, Shoji Kuwahara, Michihiro Hosojima, Tomomi Ishikawa, Ryohei Kaseda, Piyali Sarkar, Yusuke Yoshioka, Hideyuki Kabasawa, Tomomichi Iida, Sawako Goto, Koji Toba, Yuki Higuchi, Yoshiki Suzuki, Masanori Hara, Hiroyuki Kurosawa, Ichiei Narita, Yoshiaki Hirayama, Takahiro Ochiya, Akihiko Saito
Efficient biomarkers for diabetic nephropathy (DN) have not been established. Using enzyme-linked immunosorbent assay, we found previously that urinary levels of full-length megalin (C-megalin), a multiligand endocytic receptor in proximal tubules, was positively correlated with DN progression in type 2 diabetes mellitus (T2DM). Here, we found that urinary extracellular vesicle (UEV) excretion and C-megalin content in UEVs or in their exosomal fraction increased along with the progression of the albuminuric stages in T2DM patients...
March 13, 2017: Diabetes
https://www.readbyqxmd.com/read/28283950/caveolin-1-in-the-pathogenesis-of-diabetic-nephropathy-potential-therapeutic-target
#16
REVIEW
Richard Van Krieken, Joan C Krepinsky
PURPOSE OF REVIEW: Diabetic nephropathy, a major microvascular complication of diabetes and the most common cause of end-stage renal disease, is characterized by prominent accumulation of extracellular matrix. The membrane microdomains caveolae, and their integral protein caveolin-1, play critical roles in the regulation of signal transduction. In this review we discuss current knowledge of the contribution of caveolin-1/caveolae to profibrotic signaling and the pathogenesis of diabetic kidney disease, and assess its potential as a therapeutic target...
March 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28277542/microrna-27a-promotes-podocyte-injury-via-ppar%C3%AE-mediated-%C3%AE-catenin-activation-in-diabetic-nephropathy
#17
Zhanmei Zhou, Jiao Wan, Xiaoyan Hou, Jian Geng, Xiao Li, Xiaoyan Bai
Podocyte injury has a pivotal role in the pathogenesis of diabetic nephropathy (DN). MicroRNA-27a (miR-27a), peroxisome proliferator-activated receptor γ (PPARγ) and β-catenin pathways have been involved in the pathogenesis of DN. Herein, we asked whether miR-27a mediates podocyte injury through PPARγ/β-catenin signaling in DN. The functional relevance of miR-27a, PPARγ and β-catenin were investigated in cultured podocytes and glomeruli of diabetic rats and patients using in vitro and in vivo approaches...
March 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28272773/comparative-rna-seq-transcriptome-analyses-reveal-distinct-metabolic-pathways-in-diabetic-nerve-and-kidney-disease
#18
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
#19
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/28262777/the-role-of-the-complement-system-in-diabetic-nephropathy
#20
REVIEW
Allan Flyvbjerg
The development of type 1 and type 2 diabetes mellitus has a substantial negative impact on morbidity and mortality and is responsible for substantial individual and socioeconomic costs worldwide. One of the most serious consequences of diabetes mellitus is the development of diabetic angiopathy, which manifests clinically as microvascular and macrovascular complications. One microvascular complication, diabetic nephropathy, is the most common cause of end-stage renal disease in developed countries. Although several available therapeutic interventions can delay the onset and progression of diabetic nephropathy, morbidity associated with this disease remains high and new therapeutic approaches are needed...
May 2017: Nature Reviews. Nephrology
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