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Diabetic nephropathy Tubule

Zezhao Li, Zhen Hong, Zhiqing Peng, Yongcai Zhao, Rusheng Shao
Diabetic nephropathy (DN) is the major cause of end-stage renal disease in diabetic patients. Zicao, a well-known Chinese traditional medicine, has attracted much attention due to its beneficial effects in various medical fields. In this study, we attempted to investigate the effects and mechanisms of action of acetylshikonin, the main ingredient of Zicao, on renal dysfunction in DN. Our results showed that administration with acetylshikonin not only decreased blood urea nitrogen, urine creatinine and the mean kidney-to-body weight ratio in streptozotocin-induced diabetic mice, but also restored the loss of body weight, whereas the blood glucose was not changed...
March 17, 2018: Human Cell
Michelangelo Nigro, Davide Viggiano, Vincenzo Ragone, Tiziana Trabace, Annamaria di Palma, Michele Rossini, Giovambattista Capasso, Loreto Gesualdo, Giuseppe Gigliotti
BACKGROUND: The classical approach to the analysis of kidney biopsies is based on semi-quantitative scores of the amount of sclerosis, inflammatory infiltrate, fibrosis and vascular damage. However, advanced renal lesions may be accompanied by a paucity of clinical features and, conversely, important clinical abnormalities may be accompanied by minimal histopathological changes. The objective of this study is to correlate new, semiautomatic, quantitative features of kidney biopsies (e...
March 14, 2018: BMC Nephrology
Yanting Yu, Feng Bai, Nan Qin, Wenjin Liu, Qi Sun, Yang Zhou, Junwei Yang
BACKGROUND: Renal fibrosis is a common outcome of nearly all kinds of chronic kidney disease (CKD) and eventually progresses to end-stage renal disease. The identification of an optimal biomarker of renal fibrosis to replace the invasive renal biopsy will have important clinical implications. METHODS: We isolated urinary exosomes from 50 participants and examined the exosomal protein content and particle number in 38 CKD patients with different degrees of renal fibrosis and in 12 normal individuals...
March 14, 2018: Nephron
K Johanna R Hoyer, Sebastian Dittrich, Malte P Bartram, Markus M Rinschen
Renal diseases are driven by alterations in the entity of proteins within the kidney, at the level of single cells, nephron subunits (such as glomerulus and tubule), tissues and body fluids. Histologically, kidney diseases are extremely heterogeneous. Mass-spectrometry based proteomics provides a unique opportunity to interrogate heterogeneity and dynamics of various proteome layers within the kidney to better understand physiology and pathophysiology, and to translate signaling networks into therapies. Yet, the success of this endeavor will largely depend on improving proteomic data acquisition methods toward increased reproducibility...
March 6, 2018: Journal of Proteomics
Ivana Kristina Delic Jukic, Sandra Kostic, Natalija Filipovic, Larissa Gudelj Ensor, Marijeta Ivandic, Josefina Josipa Dukic, Marija Vitlov Uljevic, Lejla Ferhatovic Hamzic, Livia Puljak, Katarina Vukojevic
Background: Diabetic nephropathy (DN) is a common complication of diabetes mellitus (DM). We studied the expression of special AT-rich sequence binding protein 1 (SATB1) and phosphatase and tensin homologue (PTEN) in the kidneys of diabetic rats during ageing. Methods: Male Sprague Dawley rats were injected with 55 mg/kg streptozotocin (STZ) (DM group) or with citrate buffer (control group). Kidneys were collected after 2 weeks, 6 months and 12 months, and were analysed in three different kidney structures: glomeruli, proximal (PCT) and distal convoluted tubules (DCT)...
March 1, 2018: Nephrology, Dialysis, Transplantation
Xiao Li, Liting Xu, Xiaoyan Hou, Jian Geng, Jianwei Tian, Xiaoting Liu, Xiaoyan Bai
AIMS: Diabetic nephropathy (DN) is the most common microvascular complications and the principal cause of mortality and morbidity in patients with diabetes. The expression of advanced oxidation protein products (AOPPs) has been found in vacuolated renal tubules in DN and correlated with patients' decreased renal function. The accumulation of AOPPs is regarded as an initiating factor in podocyte injuries via the protein kinase C (PKC) signaling, which plays a critical role in triggering oxidative stress and mitochondrial injuries in diseases including DN...
February 26, 2018: Antioxidants & Redox Signaling
Kaoru Toyoda, Yusuke Suzuki, Kyotaka Muta, Taku Masuyama, Kochi Kakimoto, Akio Kobayashi, Toshiyuki Shoda, Shoichiro Sugai
Diabetic nephropathy (DN) is one of the complications of diabetes and is now the most common cause of end-stage renal disease. Fructose is a simple carbohydrate that is present in fruits and honey and is used as a sweetener because of its sweet taste. Fructose has been reported to have the potential to progress diabetes and DN in humans even though fructose itself does not increase postprandial plasma glucose levels. In this study, we investigated the effects of high fructose intake on the kidney of the Spontaneously Diabetic Torii (SDT) rats which have renal lesions similar to those in DN patients and compared these with the effects in normal SD rats...
2018: Journal of Toxicological Sciences
Hadeer O Abou-Hany, Hoda Atef, Eman Said, Hassan Elkashef, Hatem A Salem
Diabetic Nephropathy (DN) is one of the main complications associated with diabetes mellitus. Persistently elevated blood glucose level drives histopathological changes in renal tissues that hinder normal kidney functions. In the current study, crocin; the main bioactive constituent of Crocus sativus was investigated as a reno-protective agent against DN by virtue of its numerous pharmacological activities. Diabetes was induced in male Sprague-Dawely rats through intravenous injection of streptozocin (STZ) (50 mg/kg), DN was confirmed eight weeks post diabetes induction...
February 2, 2018: Chemico-biological Interactions
Meng Xue, Yang Li, Fang Hu, Yi-Jie Jia, Zong-Ji Zheng, Ling Wang, Yao-Ming Xue
Tubulointerstitial fibrosis (TIF) is crucial in the development of renal fibrosis in diabetic nephropathy(DN). Previous data shows that SIRT1 plays an important role on fibrosis, but the effect on TIF in DN and underlying mechanisms remains uncertain. In this study, we evaluated the vital role of SIRT1 and identified SIRT1 as a downstream target gene of microRNA-34a-5p (miR-34a-5p) in TIF of DN. The result revealed that expression of miR-34a-5p, fibronectin(FN),collagen type I (COL1) and transforming growth factor β1 (TGF-β1) were up-regulated accompanied by the corresponding down-regulation of SIRT1 in renal tissues of high fat diet and streptozotocin(HFD/STZ)induced diabetic mice with DN, and that the SIRT1 mRNA level was negatively correlated with miR-34a-5p expression in high glucose stimulated human proximal tubule cell line(HK-2) cells...
January 22, 2018: Biochemical and Biophysical Research Communications
Wei Wei, Xing-Rong An, Shi-Jie Jin, Xiao-Xue Li, Ming Xu
Insulin resistance is a critical process in the initiation and progression of diabetic nephropathy (DN). Alprostadil (Prostaglandin E1, PGE1) had protective effects on renal function. However, it is unknown whether PGE1 inhibited insulin resistance in renal tubule epithelial cells via autophagy, which plays a protective role in DN against insulin resistance. Insulin resistance was induced by palmitic acid (PA) in human HK-2 cells, shown as the decrease of insulin-stimulated AKT phosphorylation, glucose transporter-4 (GLUT4), glucose uptake and enhanced phosphorylation of insulin receptor substrate 1(IRS-1) at site serine 307 (pIRS-1ser307) and downregulated expression of IRS-1...
January 8, 2018: Scientific Reports
Yuna Tong, Junlan Chuan, Lan Bai, Jianyou Shi, Lei Zhong, Xingmei Duan, Yuxuan Zhu
Hyperglycemia-induced oxidative stress is thought to play a critical role in the pathogenesis of diabetic nephropathy (DN). Treating high-glucose (HG)-induced proximal tubule injury has become a patential therapeutic option to attenuate the onset and progression of DN. The present study aimed to investigate the renoprotective effect of shikonin, the chief active compound extracted from the roots of the traditional Chinese herb Lithospermum erythrorhizon, on HG-induced cytotoxicity in NRK-52E cells. Treating cells with HG significantly reduce cell viability while also significantly increasing content of reactive oxygen species (ROS)...
January 2, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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...
January 3, 2018: Angiogenesis
Theun de Groot, Lars Damen, Leanne Kosse, Mohammad Alsady, Rosalinda Doty, Ruben Baumgarten, Susan Sheehan, Johan van der Vlag, Ron Korstanje, Peter M T Deen
Glycogen synthase kinase 3 (GSK3) plays an important role in the development of diabetes mellitus and renal injury. GSK3 inhibition increases glucose uptake in insulin-insensitive muscle and adipose tissue, while it reduces albuminuria and glomerulosclerosis in acute kidney injury. The effect of chronic GSK3 inhibition in diabetic nephropathy is not known. We tested the effect of lithium, the only clinical GSK3 inhibitor, on the development of diabetes mellitus and kidney injury in a mouse model of diabetic nephropathy...
2017: PloS One
Heba Al-Hussaini, Narayana Kilarkaje
Hyperglycemia induces the formation of advanced glycation end products (AGEs) and their receptors (RAGEs), which alter several intracellular signaling mechanisms leading to the onset and progression of diabetic nephropathy. The present study focused on, i) modulatory effects of trans-resveratrol (3,5,4'-trihydroxy-trans-stilbene) on structural changes, AGE (NƐ -carboxymethyl-lysine), RAGE, oxidative stress and DNA damage, and apoptosis, and ii) localization of fibrotic changes, AGE, RAGE, 8-oxo-dG and 4-hydroxynonenal (4-HNE) in diabetic rat kidneys...
January 15, 2018: Toxicology and Applied Pharmacology
Milton Packer
Diabetes is characterized by increased activity of the sodium-hydrogen exchanger (NHE) in the glomerulus and renal tubules, which contributes importantly to the development of nephropathy. Despite the established role played by the exchanger in experimental studies, it has not been specifically targeted by those seeking to develop novel pharmacological treatments for diabetes. This review demonstrates that many existing drugs that are commonly prescribed to patients with diabetes act on the NHE1 and NHE3 isoforms in the kidney...
April 2018: Diabetes, Obesity & Metabolism
F Chiazza, A S Cento, D Collotta, D Nigro, G Rosa, F Baratta, V Bitonto, J C Cutrin, M Aragno, R Mastrocola, M Collino
Pyridoxamine, a structural analog of vitamin B6 that exerts antiglycative effects, has been proposed as supplementary approach in patients with initial diabetic nephropathy. However, the molecular mechanism(s) underlying its protective role has been so far slightly examined. C57Bl/6J mice were fed with a standard diet (SD) or a diet enriched in fat and fructose (HD) for 12 weeks. After 3 weeks, two subgroups of SD and HD mice started pyridoxamine supplementation (150 mg/kg/day) in the drinking water. HD fed mice showed increased body weight and impaired glucose tolerance, whereas pyridoxamine administration significantly improved insulin sensitivity, but not body weight, and reduced diet-induced increase in serum creatinine and urine albumin...
2017: BioMed Research International
Shuiling Zhao, Anindya Ghosh, Chao-Sheng Lo, Isabelle Chenier, James W Scholey, Janos G Filep, Julie R Ingelfinger, Shao-Ling Zhang, John S D Chan
We investigated the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in renin-angiotensin system (RAS) gene expression in renal proximal tubule cells (RPTCs) and in the development of systemic hypertension and kidney injury in diabetic Akita mice. We used adult male Akita Nrf2 knockout mice and Akita mice treated with trigonelline (an Nrf2 inhibitor) or oltipraz (an Nrf2 activator). We also examined rat immortalized RPTCs (IRPTCs) stably transfected with control plasmids or plasmids containing rat angiotensinogen (Agt), angiotensin-converting enzyme (ACE), angiotensin-converting enzyme-2 (Ace2), or angiotensin 1-7 (Ang 1-7) receptor (MasR) gene promoters...
February 1, 2018: Endocrinology
Yoshifumi Kurosaki, Akemi Imoto, Fumitaka Kawakami, Masanori Yokoba, Tsuneo Takenaka, Takafumi Ichikawa, Masato Katagiri, Naohito Ishii
Megalin, an endocytic receptor expressed in proximal tubule cells, plays a critical role in renal tubular protein reabsorption and is associated with in the albuminuria observed in diabetic nephropathy. We have previously reported increased oxidant production in the renal cortex during the normoalbuminuric stage of diabetes mellitus (DM); however, the relationship between oxidative stress and renal megalin expression during the normoalbuminuric stage of DM remains unclear. In the present study, we evaluated whether oxidative stress affects megalin expression in the normoalbuminuric stage of DM in a streptozotocin-induced diabetic rat model and in immortalized human proximal tubular cells (HK-2)...
November 29, 2017: American Journal of Physiology. Renal Physiology
Weiqin Yin, Shiqing Xu, Zai Wang, Honglin Liu, Liang Peng, Qing Fang, Tingting Deng, Wenjian Zhang, Jinning Lou
GLP-1-based treatment improves glycemia through stimulation of insulin secretion and inhibition of glucagon secretion. Recently, more and more findings showed that GLP-1 could also protect kidney from diabetic nephropathy. Most of these studies focused on glomeruli, but the effect of GLP-1 on tubulointerstitial and tubule is not clear yet. In this study, we examined the renoprotective effect of recombinant human GLP-1 (rhGLP-1), and investigated the influence of GLP-1 on inflammation and tubulointerstitial injury using diabetic nephropathy rats model of STZ-induced...
November 12, 2017: Biochemical and Biophysical Research Communications
Yingjie Han, Nguyen D K Ly, Greg H Tesch, Philip Poronnik, David J Nikolic-Paterson
Tubular epithelial cells take up and degrade plasma albumin filtered by the glomerulus. Tubular damage resulting in reduced albumin uptake or degradation has been suggested as one mechanism contributing to albuminuria in kidney disease. This study investigated whether tubular albumin uptake or degradation is altered in acute and chronic glomerular disease. Mouse models of acute glomerular injury (anti-GBM disease and LPS-induced albuminuria) and chronic disease (streptozotocin-induced diabetes and db/db mice) were examined...
March 2018: Clinical and Experimental Pharmacology & Physiology
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