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https://www.readbyqxmd.com/read/28229902/impact-of-high-glucose-and-ages-on-cultured-kidney-derived-cells-effects-on-cell-viability-lysosomal-enzymes-and-effectors-of-cell-signaling-pathways
#1
Giovani B Peres, Nestor Schor, Yara M Michelacci
We have previously reported decreased expression and activities of lysosomal cathepsins B and L in diabetic kidney. Relevant morphological changes were observed in proximal tubules, suggesting that these cells are implicated in the early stages of the disease. The aim of the present study was to investigate the mechanisms that lead to these changes. The effects of high glucose (HG) and advanced glycation end products (AGEs) on cell viability, lysosomal enzymes and other effectors of cell signaling of cultured kidney cells were studied...
February 13, 2017: Biochimie
https://www.readbyqxmd.com/read/28228403/antenatal-betamethasone-attenuates-the-angiotensin-1-7-mas-receptor-nitric-oxide-axis-in-isolated-proximal-tubule-cells
#2
Yixin Su, Jianli Bi, Victor M Pulgar, Mark C Chappell, James C Rose
We previously reported a sex-specific effect of antenatal treatment with betamethasone (Beta) on sodium (Na(+)) excretion in adult sheep whereby treated males but not females had an attenuated natriuretic response to Ang-(1-7). The present study determined the Na(+) uptake and nitric oxide (NO) response to low dose Ang-(1-7) (1 pM) in renal proximal tubule cells (RPTC) from adult male and female sheep antenatally exposed to Beta or vehicle. Data were expressed as % of basal uptake or area under the curve (AUC) for Na(+) or % of control for NO...
February 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28215940/elf5-is-a-principal-cell-lineage-specific-transcription-factor-in-the-kidney-that-contributes-to-aqp2-and-avpr2-gene-expression
#3
Justin Grassmeyer, Malini Mukherjee, Jennifer deRiso, Casey Hettinger, Monica Bailey, Satrajit Sinha, Jane E Visvader, Haotian Zhao, Eric Fogarty, Kameswaran Surendran
The mammalian kidney collecting ducts are critical for water, electrolyte and acid-base homeostasis and develop as a branched network of tubular structures composed of principal cells intermingled with intercalated cells. The intermingled nature of the different collecting duct cell types has made it challenging to identify unique and critical factors that mark and/or regulate the development of the different collecting duct cell lineages. Here we report that the canonical Notch signaling pathway components, RBPJ and Presinilin1 and 2, are involved in patterning the mouse collecting duct cell fates by maintaining a balance between principal cell and intercalated cell fates...
February 17, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28139717/deferasirox-induced-iron-depletion-promotes-bclxl-downregulation-and-death-of-proximal-tubular-cells
#4
Diego Martin-Sanchez, Angel Gallegos-Villalobos, Miguel Fontecha-Barriuso, Susana Carrasco, Maria Dolores Sanchez-Niño, Francisco J Lopez-Hernandez, Marta Ruiz-Ortega, Jesus Egido, Alberto Ortiz, Ana Belén Sanz
Iron deficiency has been associated with kidney injury. Deferasirox is an oral iron chelator used to treat blood transfusion-related iron overload. Nephrotoxicity is the most serious and common adverse effect of deferasirox and may present as an acute or chronic kidney disease. However, scarce data are available on the molecular mechanisms of nephrotoxicity. We explored the therapeutic modulation of deferasirox-induced proximal tubular cell death in culture. Deferasirox induced dose-dependent tubular cell death and AnexxinV/7AAD staining showed features of apoptosis and necrosis...
January 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28123498/allicin-inhibits-tubular-epithelial-myofibroblast-transdifferentiation-under-high-glucose-conditions-in-vitro
#5
Hong Huang, Fenping Zheng, Xuehong Dong, Fang Wu, Tianfeng Wu, Hong Li
Previous studies have suggested that tubular epithelial-mesenchymal transition (EMT) is an important event in renal tubulointerstitial fibrosis, which is a clinical characteristic of diabetic nephropathy. The present study aimed to investigate the effect of allicin, the major biological active component of garlic, on the EMT of a human renal proximal tubular epithelial cell line (HK-2) cultured under high glucose concentrations. HK-2 cells were exposed for 48 h to 5.5 or 25 mmol/l D-glucose, 25 mmol/l D-glucose plus allicin (2...
January 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28116710/measurement-of-angiotensin-converting-enzyme-2-activity-in-biological-fluid-ace2
#6
Fengxia Xiao, Kevin D Burns
Angiotensin-converting enzyme 2 (ACE2) is a recently described member of the renin-angiotensin system that hydrolyzes angiotensin (Ang) II to Ang-(1-7), and may thereby protect against cardiovascular and renal diseases. ACE2 is a type 1 integral membrane protein and contains a catalytically active ectodomain that can be shed from the cell surface into the extracellular space, via cleavage by a disintegrin and metalloproteinase-17 (ADAM-17). ACE2 enzymatic activity and protein can be detected in biological fluids, including urine, plasma, and conditioned cell culture media...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28116093/inhibition-of-sglt2-alleviates-diabetic-nephropathy-by-suppressing-high-glucose-induced-oxidative-stress-in-type-1-diabetic-mice
#7
Takashi Hatanaka, Daisuke Ogawa, Hiromi Tachibana, Jun Eguchi, Tatsuyuki Inoue, Hiroshi Yamada, Kohji Takei, Hirofumi Makino, Jun Wada
It is unclear whether the improvement in diabetic nephropathy by sodium glucose cotransporter 2 (SGLT2) inhibitors is caused by a direct effect on SGLT2 or by the improvement in hyperglycemia. Here, we investigated the effect of dapagliflozin on early-stage diabetic nephropathy using a mouse model of type 1 diabetes and murine proximal tubular epithelial cells. Eight-week-old Akita mice were treated with dapagliflozin or insulin for 12 weeks. Body weight, urinary albumin excretion, blood pressure, as well as levels of blood glucose and hemoglobin A1c were measured...
August 2016: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28094285/urinary-exosomes-contain-micrornas-capable-of-paracrine-modulation-of-tubular-transporters-in-kidney
#8
Tannia Gracia, Xiaonan Wang, Ya Su, Elizabeth E Norgett, Timothy L Williams, Pablo Moreno, Gos Micklem, Fiona E Karet Frankl
Exosomes derived from all nephron segments are present in human urine, where their functionality is incompletely understood. Most studies have focused on biomarker discovery rather than exosome function. Through sequencing we identified the miRNA repertoire of urinary exosomes from healthy volunteers; 276 mature miRNAs and 345 pre-miRNAs were identified (43%/7% of reads). Among the most abundant were members of the miR-10, miR-30 and let-7 families. Targets for the identified miRNAs were predicted using five different databases; genes encoding membrane transporters and their regulators were enriched, highlighting the possibility that these miRNAs could modulate key renal tubular functions in a paracrine manner...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28093887/collagen-hydrogel-scaffold-promotes-mesenchymal-stem-cell-and-endothelial-cell-coculture-for-bone-tissue-engineering
#9
Bao-Ngoc B Nguyen, Rebecca A Moriarty, Tim Kamalitdinov, Julie M Etheridge, John P Fisher
The generation of functional, vascularized tissues is a key challenge for the field of tissue engineering. Before clinical implantations of such tissue engineered bone constructs can succeed, tactics to promote neovascularization need to be strengthened. We have previously demonstrated that the tubular perfusion system (TPS) bioreactor is an effective culturing method to augment osteogenic differentiation and maintain viability of human mesenchymal stem cells (hMSC). Here, we devised a strategy to address the need for a functional microvasculature by designing an in vitro coculture system that simultaneously cultures osteogenic differentiating hMSCs with endothelial cells (ECs)...
April 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28024839/pink1-parkin-mediated-mitophagy-play-a-protective-role-in-cisplatin-induced-renal-tubular-epithelial-cells-injury
#10
Chuanyan Zhao, Zhuyun Chen, Xueqiang Xu, Xiaofei An, Suyan Duan, Zhimin Huang, Chengning Zhang, Lin Wu, Bo Zhang, Aihua Zhang, Changying Xing, Yanggang Yuan
Cisplatin often causes acute kidney injury (AKI) in the treatment of a wide variety of malignancies. Mitochondrial dysfunction is one of the main reasons for cisplatin nephrotoxicity. Previous study showed that Pink1 and Parkin play central roles in regulating the mitophagy, which is a key protective mechanism by specifically eliminating dysfunctional or damaged mitochondria. However, the mechanisms that modulate mitophagy in cisplatin induced nephrotoxicity remain to be elucidated. The purpose of this study was to investigate the effects of Pink1/Parkin pathway in mitophagy, mitochondrial dysfunction and renal proximal tubular cells injury during cisplatin treatment...
December 23, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/28006785/mir-155-is-involved-in-renal-ischemia-reperfusion-injury-via-direct-targeting-of-foxo3a-and-regulating-renal-tubular-cell-pyroptosis
#11
Haoyu Wu, Tao Huang, Liang Ying, Conghui Han, Dawei Li, Yao Xu, Ming Zhang, Shan Mou, Zhen Dong
BACKGROUND/AIMS: Ischemia/reperfusion injury (IRI) plays a crucial role in renal transplantation and can cause renal failure associated with pyroptosis, a pro-inflammatory-induced programmed cell death. Small endogenous non-coding RNAs have been shown to be involved in renal ischemia/reperfusion injury. This study was performed to investigate which miRNAs regulate pyroptosis in response to renal ischemia/reperfusion injury and determine the mechanism underlying this regulation. METHODS: An in vivo rat model of renal IRI was established, and the serum and kidneys were harvested 24 h after reperfusion to assess renal function and histological changes...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28003188/insulin-like-growth-factor-binding-protein-7-and-tissue-inhibitor-of-metalloproteinases-2-differential-expression-and-secretion-in-human-kidney-tubule-cells
#12
David R Emlet, Nuria Pastor-Soler, Allison Marciszyn, Xiaoyan Wen, Hernando Gomez, William H Humphries, Seth Morrisroe, Jacob K Volpe, John A Kellum
We have characterized the expression and secretion of the acute kidney injury (AKI) biomarkers insulin-like growth factor binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) in human kidney epithelial cells in primary cell culture and tissue. We established cell culture model systems of primary kidney cells of proximal and distal tubule origin and observed that both proteins are indeed expressed and secreted in both tubule cell types in vitro. However, TIMP-2 is both expressed and secreted preferentially by cells of distal tubule origin, while IGFBP7 is equally expressed across tubule cell types yet preferentially secreted by cells of proximal tubule origin...
February 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27997859/interleukin-1%C3%AE-as-a-driver-of-renal-ngal-production
#13
Mathilde L Bonnemaison, Eileen S Marks, Erika I Boesen
Neutrophil gelatinase-associated lipocalin (NGAL) is increasingly regarded as a biomarker of acute kidney injury, or kidney injury in general, but the stimuli responsible for its production are incompletely understood. This study tested the relationship between the pro-inflammatory cytokine interleukin-1β (IL-1β) and both circulating and renal NGAL, using chronic subcutaneous infusion of IL-1β in mice and tissue culture of renal cell lines. Following a 14-day subcutaneous infusion of vehicle or IL-1β (10ng/h) in male C57Bl/6 mice, a striking positive correlation (r(2)=0...
December 17, 2016: Cytokine
https://www.readbyqxmd.com/read/27965087/ship-a-novel-factor-to-ameliorate-extracellular-matrix-accumulation-via-suppressing-pi3k-akt-ctgf-signaling-in-diabetic-kidney-disease
#14
Fan Li, Lisha Li, Meijuan Cheng, Xiumin Wang, Jun Hao, Shuxia Liu, Huijun Duan
Tubular interstitial extracellular matrix accumulation, which plays a key role in the pathogenesis and progression of diabetic kidney disease (DKD), is believed to be mediated by activation of PI3K/Akt signal pathway. However, it is still not clear whether SH2 domain-containing inositol 5'-phosphatase (SHIP), known as a negative regulator of PI3K/Akt pathway is also involved in extracellular matrix metabolism of diabetic kidney. In the present study, decreased SHIP and increased phospho-Akt (Ser 473, Thr 308) were found in renal tubular cells of diabetic mice accompanied by overexpression of connective tissue growth factor (CTGF) and extracellular matrix deposition versus normal mice...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27941350/pentraxin-3-activates-jnk-signaling-and-regulates-the-epithelial-to-mesenchymal-transition-in-renal-fibrosis
#15
Tung-Wei Hung, Jen-Pi Tsai, Shin-Huey Lin, Chien-Hsing Lee, Yi-Hsien Hsieh, Horng-Rong Chang
BACKGROUND/AIMS: Tubulointerstitial fibrosis can lead to end-stage renal disease. Pentraxin 3 (PTX3) is an acute phase protein produced by resident and innate immunity cells. We investigated the effect of PTX3 on cultured human proximal tubular epithelial (HK-2) cells and a rat unilateral ureteral obstruction (UUO) model of renal fibrosis. METHODS: Gain-of-function experiments were used to examine the effect of recombinant human PTX3 (Rh-PTX3) on HK-2 cells. Cell proliferation (MTT assay) and in vitro cell migration were measured...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27924932/nadph-oxidase-4-deficiency-increases-tubular-cell-death-during-acute-ischemic-reperfusion-injury
#16
Stellor Nlandu-Khodo, Romain Dissard, Udo Hasler, Matthias Schäfer, Haymo Pircher, Pidder Jansen-Durr, Karl Heinz Krause, Pierre-Yves Martin, Sophie de Seigneux
NADPH oxidase 4 (NOX4) is highly expressed in kidney proximal tubular cells. NOX4 constitutively produces hydrogen peroxide, which may regulate important pro-survival pathways. Renal ischemia reperfusion injury (IRI) is a classical model mimicking human ischemic acute tubular necrosis. We hypothesized that NOX4 plays a protective role in kidney IRI. In wild type (WT) animals subjected to IRI, NOX4 protein expression increased after 24 hours. NOX4 KO (knock-out) and WT littermates mice were subjected to IRI...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27880866/tgf-%C3%AE-1-stimulates-movement-of-renal-proximal-tubular-epithelial-cells-in-a-three-dimensional-cell-culture-via-an-autocrine-tgf-%C3%AE-2-production
#17
Deyi Luo, Qiunong Guan, Kunjie Wang, Christopher Y C Nguan, Caigan Du
TGF-βs are multifunctional cytokines, but their roles in human renal homeostasis are not fully understood. This study investigated the role of TGF-β1 in the movement of human renal proximal tubular epithelial cells (PTECs) in a three-dimensional (3D) model. HKC-8 cells, a human PTEC line, were grown in a 3D collagen culture system. Cell movement was observed under a microscope. The gene expression was examined using PCR Arrays or qRT-PCR, and protein levels by Western blot. Here, we showed that the tight junction structure formed between adjacent cells of a HKC-8 cell colony in 3D cultures, and TGF-β1 stimulated their movement, evidenced by the appearance of fingerlike pseudopodia in the leader cells at the edge of the colonies...
January 1, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/27872161/identification-of-urinary-exosomal-noncoding-rnas-as-novel-biomarkers-in-chronic-kidney-disease
#18
Rimpi Khurana, Glory Ranches, Simon Schafferer, Melanie Lukasser, Michael Rudnicki, Gert Mayer, Alexander Hüttenhofer
In chronic kidney disease (CKD), the decline in the glomerular filtration rate is associated with increased morbidity and mortality and thus poses a major challenge for healthcare systems. While the contribution of tissue-derived miRNAs and mRNAs to CKD progression has been extensively studied, little is known about the role of urinary exosomes and their association with CKD. Exosomes are small, membrane-derived endocytic vesicles that contribute to cell-to-cell communication and are present in various body fluids, such as blood or urine...
February 2017: RNA
https://www.readbyqxmd.com/read/27867451/thioredoxin-interacting-protein-mediates-nlrp3-inflammasome-activation-involved-in-the-susceptibility-to-ischemic-acute-kidney-injury-in-diabetes
#19
Ye Da Xiao, Ya Yi Huang, Hua Xin Wang, Yang Wu, Yan Leng, Min Liu, Qian Sun, Zhong-Yuan Xia
Kidney in diabetic state is more sensitive to ischemic acute kidney injury (AKI). However, the underlying mechanisms remain unclear. Herein, we examined the impact of diabetes mellitus on thioredoxin-interacting protein (TXNIP) expression and whether mediated NLRP3 activation was associated with renal ischemia/reperfusion- (I/R-) induced AKI. In an in vivo model, streptozotocin-induced diabetic rats showed higher susceptibility to I/R injury with increased TXNIP expression, which was significantly attenuated by resveratrol (RES) treatment (10 mg/kg intraperitoneal daily injection for 7 consecutive days prior to I/R induction)...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27861627/caspase-dependent-and-caspase-independent-pathways-are-involved-in-cadmium-induced-apoptosis-in-primary-rat-proximal-tubular-cell-culture
#20
Gang Liu, Hui Zou, Tongwang Luo, Mengfei Long, Jianchun Bian, Xuezhong Liu, Jianhong Gu, Yan Yuan, Ruilong Song, Yi Wang, Jiaqiao Zhu, Zongping Liu
We designed this study to investigate whether cadmium induces caspase-independent apoptosis and to investigate the relationship between the caspase-dependent and caspase-independent apoptotic pathways. Cadmium (1.25-2.5 μM) induced oxidative stress in rat proximal tubular (rPT) cells, as seen in the reactive oxygen species levels; N-acetylcysteine prevented this. Cyclosporin A (CsA) prevented mitochondrial permeability transition pore opening and apoptosis; there was mitochondrial ultrastructural disruption, mitochondrial cytochrome c (cyt c) translocation to the cytoplasm, and subsequent caspase-9 and caspase-3 activation...
2016: PloS One
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