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Diabetic nephropathy pathological pathways

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https://www.readbyqxmd.com/read/29643035/-correlation-between-expressions-of-vegf-and-trpc6-and-their-roles-in-podocyte-injury-in-rats-with-diabetic-nephropathy
#1
Xiao-Na Zhu, Yu-Huan Wang, Juan-Juan Wu, Peng Dong, Min Zhang
OBJECTIVE: To analyze the correlation between the expressions of vascular endothelial growth factor (VEGF) and transient receptor potential canonical 6 (TRPC6) and their role in podocyte injury in rats with diabetic nephropathy. METHODS: Forty SD rats with diabetic nephropathy induced by intraperitoneal injection of 65 mg/kg streptozotocin were randomized equally into 5 groups, including a diabetic nephropathy model group and 4 treatment groups, with 8 normal SD rats as the normal control group...
March 20, 2018: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/29607573/lithium-and-nephrotoxicity-unravelling-the-complex-pathophysiological-threads-of-the-lightest-metal
#2
REVIEW
J Davis, M Desmond, M Berk
While lithium remains the most efficacious treatment for bipolar disorder, it can cause significant nephrotoxicity. The molecular mechanisms behind both this process and the development of nephrogenic diabetes insipidus still remain to be fully elucidated but appear to involve alterations in glycogen synthase kinase 3 signalling, G2 cell cycle progression arrest, alterations in inositol and prostaglandin signalling pathways, and dysregulated trafficking and transcription of aquaporin 2 water channels. The end result of this is a tubulointerstitial nephropathy with microcyst formation and relative glomerular sparing, both visible on pathology specimens and increasingly noted on non-invasive imaging...
April 1, 2018: Nephrology
https://www.readbyqxmd.com/read/29581743/-tripterygium-wilfordii-mitigates-hyperglycemia-induced-upregulated-wnt-%C3%AE-catenin-expression-and-kidney-injury-in-diabetic-rats
#3
Baochao Chang, Weidong Chen, Yan Zhang, Ping Yang, Lei Liu
Aberrant activation of the Wnt/β-catenin pathway contributes to the development of diabetic nephropathy (DN); however, treatment with Tripterygium wilfordii (TW) may be beneficial for patients with DN. The aim of the present study was to evaluate the effect of TW on Wnt/β-catenin expression in the kidneys of diabetic rats. Male Sprague-Dawley rats were randomly injected with vehicle (control) or streptozotocin to induce diabetes. Diabetic rats were then randomly treated with vehicle (sodium carboxymethyl cellulose; SCC), TW combined with SCC (8 or 16 mg/kg) or irbesartan (50 mg/kg) daily for 8 weeks...
April 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29552086/effect-of-qufengtongluo-decoction-on-pi3k-akt-signaling-pathway-in-the-kidney-of-type-2-diabetes-mellitus-rat-gk-rat-with-diabetic-nephropathy
#4
Wei-Jun Huang, Qiang Fu, Yong-Hua Xiao, Qing Gong, Wen-Jing Wu, Zi-Long Shen, Hua Zhang, Xu Jia, Xue-Min Huang, Ya-Xin Zhang, Jin-Xi Zhao, Shi-Dong Wang, Mian Jia, Yu-Ting Zhang
Qufengtongluo (QFTL) decoction is an effective treatment for diabetic nephropathy (DN). However, the underlying molecular mechanism is still unclear. In this study, we try to investigate whether QFTL decoction acts via inhibiting PI3K/Akt signaling pathway. Twenty-four GK rats were randomly divided into 3 groups: blank group, sham-operated group, and QFTL group. After model establishment, rats in QFTL group were given QFTL decoction by gavage, while the rest were given pure water. During the 8-week intervention, 24 hr urinal protein was measured every 2-3 weeks...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29540859/socs1-targeted-therapy-ameliorates-renal-and-vascular-oxidative-stress-in-diabetes-via-stat1-and-pi3k-inhibition
#5
Laura Lopez-Sanz, Susana Bernal, Carlota Recio, Iolanda Lazaro, Ainhoa Oguiza, Ana Melgar, Luna Jimenez-Castilla, Jesus Egido, Carmen Gomez-Guerrero
Oxidative stress resulting from excessive production of reactive oxygen species (ROS) or impaired antioxidant defenses is closely related to the development of diabetic vascular complications, including nephropathy and atherosclerosis. Chronic activation of Janus kinase/Signal transducer and activator of transcription (JAK/STAT) signaling pathway contributes to diabetic complications by inducing expression of genes involved in cell proliferation, fibrosis, inflammation, and oxidative stress. Suppressors of cytokine signaling (SOCS) family of endogenous JAK/STAT regulators is an attractive target for therapeutic intervention...
March 14, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29444469/mangiferin-prevents-diabetic-nephropathy-progression-and-protects-podocyte-function-via-autophagy-in-diabetic-rat-glomeruli
#6
Xiaodan Wang, Lihui Gao, Hua Lin, Jingling Song, Jinwen Wang, Yumin Yin, Jianghu Zhao, Xiangwei Xu, Zhenkun Li, Ling Li
Diabetic nephropathy (DN) is one of the most severe microangiopathies of diabetes mellitus and is a leading cause of end stage renal disease. Numerous studies suggest that podocyte injury contributes to progressive proteinuria. Podocytes are highly specialized, terminally differentiated cells that are unable to proliferate, autophagy plays a key role in maintaining the structure and function of podocytes. Autophagy impairment is involved in the pathogenesis of podocyte loss, which leads to massive proteinuria in DN...
February 11, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29433676/bioactive-phytochemicals-that-regulate-the-cellular-processes-involved-in-diabetic-nephropathy
#7
REVIEW
Amna Parveen, Mirim Jin, Sun Yeou Kim
BACKGROUND: Owing to the multiple causative factors, the current advances in medication for diabetic nephropathy (DN) do not appear to have improved therapies for patients. Furthermore, use of multiple synthetic medications has shown various adverse effects and ultimately leads to deterioration of the condition. Medicinal plants and their bioactive constituents are considered to be safer and more effective than synthetic medicines against various chronic diseases. Therefore, the use of natural products in the management of DN has been suggested...
January 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29425253/the-kca3-1-blocker-tram34-reverses-renal-damage-in-a-mouse-model-of-established-diabetic-nephropathy
#8
Chunling Huang, Ling Zhang, Ying Shi, Hao Yi, Yongli Zhao, Jason Chen, Carol A Pollock, Xin-Ming Chen
Despite optimal control of hyperglycaemia, hypertension, and dyslipidaemia, the number of patients with diabetic nephropathy (DN) continues to grow. Strategies to target various signaling pathways to prevent DN have been intensively investigated in animal models and many have been proved to be promising. However, targeting these pathways once kidney disease is established, remain unsatisfactory. The clinical scenario is that patients with diabetes mellitus often present with established kidney damage and need effective treatments to repair and reverse the kidney damage...
2018: PloS One
https://www.readbyqxmd.com/read/29416624/1-25-dihydroxyvitamin-d3-inhibits-the-proliferation-of-rat-mesangial-cells-induced-by-high-glucose-via-ddit4
#9
Da-Peng Chen, Ye-Ping Ma, Li Zhuo, Zheng Zhang, Gu-Ming Zou, Yue Yang, Hong-Mei Gao, Wen-Ge Li
1,25-Dihydroxyvitamin D3(1,25(OH)2 D3) is a secosteroid with antiproliferative property. It also plays a pivotal renoprotective role in diabetic nephropathy. We investigated whether 1,25(OH)2D3 could inhibit the proliferation of rat mesangial cells exposed to high glucose via the DNA-damage-inducible transcript 4/mammalian target of rapamycin(DDIT4/mTOR) pathway. The cell proliferation rate and cell cycle duration were measured using cell counting kit-8 assay and flow cytometry. Protein expression was assayed by Western blot...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29371661/cellular-death-reactive-oxygen-species-ros-and-diabetic-complications
#10
REVIEW
Caroline Maria Oliveira Volpe, Pedro Henrique Villar-Delfino, Paula Martins Ferreira Dos Anjos, José Augusto Nogueira-Machado
Chronic or intermittent hyperglycemia is associated with the development of diabetic complications. Several signaling pathways can be altered by having hyperglycemia in different tissues, producing oxidative stress, the formation of advanced glycation end products (AGEs), as well as the secretion of the pro-inflammatory cytokines and cellular death (pathological autophagy and/or apoptosis). However, the signaling pathways that are directly triggered by hyperglycemia appear to have a pivotal role in diabetic complications due to the production of reactive oxygen species (ROS), oxidative stress, and cellular death...
January 25, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29369972/mtor-inhibition-and-kidney-diseases
#11
Maggie K M Ma, Susan Yung, Tak Mao Chan
Mammalian or mechanistic target of rapamycin (mTOR) is a serine-threonine kinase that plays essential roles in cell growth, proliferation, metabolism, and survival. Increased activation of the mTOR pathway is observed in patients and animal models of renal transplant rejection, autosomal dominant polycystic kidney disease, renal cell carcinoma, diabetic nephropathy, lupus nephritis, and angiomyolipoma. Agents that inhibit mTOR, such as sirolimus and everolimus, are incorporated in immunosuppressive regimens to prevent renal allograft rejection and are often used to facilitate calcineurin inhibitor minimization or to reduce the incidence of tumor recurrence...
February 2018: Transplantation
https://www.readbyqxmd.com/read/29331868/zinc-supplementation-alleviates-the-progression-of-diabetic-nephropathy-by-inhibiting-the-overexpression-of-oxidative-stress-mediated-molecular-markers-in-streptozotocin-induced-experimental-rats
#12
Susmita Barman, Seetur R Pradeep, Krishnapura Srinivasan
Zinc deficiency during diabetes projects a role for zinc nutrition in the management of diabetic nephropathy. The current study explored whether zinc supplementation protects against diabetic nephropathy through modulation of kidney oxidative stress and stress-induced expression related to the inflammatory process in streptozotocin-induced diabetic rats. Groups of hyperglycemic rats were exposed to dietary interventions for 6 weeks with zinc supplementation (5 times and 10 times the normal level). Supplemental-zinc-fed diabetic groups showed a significant reversal of increased kidney weight and creatinine clearance...
April 2018: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29299781/slit2-robo1-signaling-is-involved-in-angiogenesis-of-glomerular-endothelial-cells-exposed-to-a-diabetic-like-environment
#13
Junhui Liu, Weiping Hou, Tao Guan, Luyao Tang, Xufei Zhu, Yi Li, Shihui Hou, Jun Zhang, Hua Chen, Yunjian Huang
Abnormal angiogenesis plays a pathological role in diabetic nephropathy (DN), contributing to glomerular hypertrophy and microalbuminuria. Slit2/Robo1 signaling participates in angiogenesis in some pathological contexts, but whether it is involved in glomerular abnormal angiogenesis of early DN is unclear. The present study evaluated the effects of Slit2/Robo1 signaling pathway on angiogenesis of human renal glomerular endothelial cells (HRGECs) exposed to a diabetic-like environment or recombinant Slit2-N...
May 2018: Angiogenesis
https://www.readbyqxmd.com/read/29242368/lessons-from-ckd-related-genetic-association-studies-moving-forward
#14
Sophie Limou, Nicolas Vince, Afshin Parsa
Over the past decade, genetic association studies have uncovered numerous determinants of kidney function in the general, diabetic, hypertensive, CKD, ESRD, and GN-based study populations ( e.g. , IgA nephropathy, membranous nephropathy, FSGS). These studies have led to numerous novel and unanticipated findings, which are helping improve our understanding of factors and pathways affecting both normal and pathologic kidney function. In this review, we report on major discoveries and advances resulting from this rapidly progressing research domain...
January 6, 2018: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/29223351/ck2%C3%AE-promotes-advanced-glycation-end-products-induced-expressions-of-fibronectin-and-intercellular-adhesion-molecule-1-via-activating-mrtf-a-in-glomerular-mesangial-cells
#15
Zhiquan Chen, Qiuhong Chen, Junying Huang, Wenyan Gong, Yezi Zou, Lei Zhang, Peiqing Liu, Heqing Huang
Advanced glycation end products' (AGEs) modification of extracellular matrix proteins induces crosslinking, which results in thickening of the basement membrane and activating several intracellular signaling cascades, eventually promoting the pathological progression of diabetic nephropathy (DN). We have previously confirmed that casein kinase 2α (CK2α) activates the nuclear factor of kappaB (NF-κB) signaling pathway to enhance high glucose-induced expressions of fibronectin (FN) and intercellular adhesion molecule-1 (ICAM-1) in glomerular mesangial cells (GMCs)...
February 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29207635/socs2-overexpression-alleviates-diabetic-nephropathy-in-rats-by-inhibiting-the-tlr4-nf-%C3%AE%C2%BAb-pathway
#16
Suxia Yang, Junwei Zhang, Shiying Wang, Xinxin Zhao, Jun Shi
Suppressor of cytokine signaling 2 (SOCS2) was reported to be involved in the development of Diabetic Nephropathy (DN). However, its underlying mechanism remains undefined. Western blot was carried out to determine the expressions of SOCS2, Toll-like receptors 4 (TLR4) and nuclear factor kappa B (NF-κB) pathway-related proteins in DN patients, streptozotocin (STZ)-induced DN rats and high glucose (HG)-stimulated podocytes. The effects of SOCS2 overexpression on renal injury, the inflammatory cytokines production, renal pathological changes, apoptosis and the TLR4/NF-κB pathway in DN rats or HG-stimulated podocytes were investigated...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29161661/chlorogenic-acid-prevents-diabetic-nephropathy-by-inhibiting-oxidative-stress-and-inflammation-through-modulation-of-the-nrf2-ho-1-and-nf-%C3%A4-b-pathways
#17
Liping Bao, Jushuang Li, Dongqing Zha, Lian Zhang, Ping Gao, Tao Yao, Xiaoyan Wu
Oxidative and inflammatory damage have been suggested to play important roles in the pathogenesis of diabetic nephropathy (DN). Chlorogenic acid (CGA) is one of the most abundant polyphenols and has known immunoprotective, antioxidant and anti-inflammatory properties. In the present study, animal experiments were designed to examine the protective effects of CGA in DN, and cellular experiments were designed to explore the underlying mechanisms. CGA significantly attenuated diabetic renal damage based on histological pathology and molecular biological methods...
January 2018: International Immunopharmacology
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
#18
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
#19
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...
December 1, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28974087/the-pathological-role-of-the-ubiquitination-pathway-in-diabetic-nephropathy
#20
REVIEW
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...
February 2018: Minerva Medica
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