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https://www.readbyqxmd.com/read/28094285/urinary-exosomes-contain-micrornas-capable-of-paracrine-modulation-of-tubular-transporters-in-kidney
#1
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/28062795/silac-based-proteomics-of-primary-human-kidney-cells-reveals-a-novel-link-between-male-sex-hormones-and-impaired-energy-metabolism-in-diabetic-kidney-disease
#2
Sergi Clotet, Maria Jose Soler, Marta Riera, Julio Pascual, Fei Fang, Joyce Zhou, Ihor Batruch, Stella K Vasiliou, Apostolos Dimitromanolakis, Clara Barrios, Eleftherios Diamandis, James Scholey, Ana Konvalinka
Male sex predisposes to many kidney diseases. Considering that androgens exert deleterious effects in a variety of cell types within kidney, we hypothesized that dihydrotestosterone (DHT) would alter the biology of the renal tubular cell by inducing changes in the proteome. We employed stable isotope labeling with amino acids (SILAC) in an indirect spike-in fashion to accurately quantify the proteome in DHT- and 17β-estradiol (EST)-treated human proximal tubular epithelial cells (PTEC). Of the 5043 quantified proteins, 76 were differentially regulated...
January 4, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28060335/identification-of-intracellular-signaling-events-induced-in-viable-cells-by-interaction-with-neighboring-cells-undergoing-apoptotic-cell-death
#3
Snezana Vujicic, Lanfei Feng, Angelika Antoni, Joyce Rauch, Jerrold S Levine
Cells dying by apoptosis, also referred to as regulated cell death, acquire multiple new activities that enable them to influence the function of adjacent live cells. Vital activities, such as survival, proliferation, growth, and differentiation, are among the many cellular functions modulated by apoptotic cells. The ability to recognize and respond to apoptotic cells appears to be a universal feature of all cells, regardless of lineage or organ of origination. However, the diversity and complexity of the response to apoptotic cells mandates that great care be taken in dissecting the signaling events and pathways responsible for any particular outcome...
December 27, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28053239/microrna-378-reduces-mesangial-hypertrophy-and-kidney-tubular-fibrosis-via-mapk-signaling
#4
Bo Wang, Kevin Yao, Andrea F Wise, Ricky Lau, Hsin-Hui Shen, Greg H Tesch, Sharon D Ricardo
AIMS: To determine the regulatory role of a novel miRNA, miR-378, in the development of fibrosis through repression of the MAPK1 (ERK2) pathway. METHODS: miR-378 and fibrotic gene expression was examined in streptozotocin (STZ)-induced diabetic mice at 18 weeks or in unilateral ureteral obstruction (UUO) mice at 7 days. miR-378 transfection of proximal tubular epithelial cells, NRK52E, and mesangial cells was assessed with/without endogenous miR-378 knockdown using the locked nucleic acid (LNA) inhibitor...
January 4, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28052987/megalin-blockade-with-cilastatin-suppresses-drug-induced-nephrotoxicity
#5
Yoshihisa Hori, Nobumasa Aoki, Shoji Kuwahara, Michihiro Hosojima, Ryohei Kaseda, Sawako Goto, Tomomichi Iida, Shankhajit De, Hideyuki Kabasawa, Reika Kaneko, Hiroyuki Aoki, Yoshinari Tanabe, Hiroshi Kagamu, Ichiei Narita, Toshiaki Kikuchi, Akihiko Saito
Nephrotoxicity induced by antimicrobial or anticancer drugs is a serious clinical problem. Megalin, an endocytic receptor expressed at the apical membranes of proximal tubules, mediates the nephrotoxicity of aminoglycosides and colistin, key antimicrobials for multidrug-resistant organisms. The mechanisms underlying the nephrotoxicity induced by vancomycin, an antimicrobial for methicillin-resistant Staphylococcus aureus, and cisplatin, an important anticancer drug, are unknown, although the nephrotoxicity of these drugs and gentamicin, an aminoglycoside, is suppressed experimentally with cilastatin...
January 4, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28049953/cobalt-chloride-induces-expression-and-function-of-breast-cancer-resistance-protein-bcrp-abcg2-in-human-renal-proximal-tubular-epithelial-cell-line-hk-2
#6
Katsuki Nishihashi, Kei Kawashima, Takami Nomura, Yumiko Urakami-Takebayashi, Makoto Miyazaki, Mikihisa Takano, Junya Nagai
The human breast cancer resistance protein (BCRP/ABCG2), a member of the ATP-binding cassette transporter family, is a drug transporter restricting absorption and enhancing excretion of many compounds including anticancer drugs. The cis-regulatory elements in the BCRP promoter include a hypoxia response element, i.e., the DNA binding site for hypoxia-inducible factor-1 (HIF-1). In this study, we investigated the effect of cobalt chloride, a chemical inducer of HIF-1α, on the expression and function of BCRP in human renal proximal tubular cell line HK-2...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28042948/bacmam-delivery-of-a-protective-gene-to-reduce-renal-ischemia-reperfusion-injury
#7
Elisabetta Hitchman, Richard Brian Hitchman, Linda A King
Ischaemia-reperfusion (I/R) injury remains the primary contributor to delayed graft function in kidney transplantation. The beneficial application of manganese superoxide dismutase (sod), delivered by a BacMam vector, against renal I/R injury has not been evaluated previously. Therefore, in this study we overexpressed sod-2 in proximal tubular epithelial (HK-2) cells and porcine kidney organs during simulated renal I/R injury. Incubation of HK-2 cells with antimycin A and 2-deoxyglucose resulted in a significant decrease in intracellular ATP levels; following reperfusion, ATP levels significantly increased overtime in cells overexpressing sod-2...
January 2, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28024839/pink1-parkin-mediated-mitophagy-play-a-protective-role-in-cisplatin-induced-renal-tubular-epithelial-cells-injury
#8
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/28003188/insulin-like-growth-factor-binding-protein-7-and-tissue-inhibitor-of-metalloproteinases-2-differential-expression-and-secretion-in-human-kidney-tubule-cells
#9
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 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...
December 21, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27998868/-the-microrna-mir-205-inhibits-epithelial-messenchymal-transition-in-hk-2-cells-by-down-regulating-zeb1-and-zeb2-expressions
#10
Luo-Yuan Cao, Jing Yang, Xian-Guo Fu, Ying-Hua Lin, Feng Lin, Bao-Ying Huang
OBJECTIVE: To explore the role of miR-205 in regulating epithelial-messenchymal transition (EMT) in proximal tubular cell line HK-2 cells and the underlying mechanism. METHODS: HK-2 cells transfected with miR-205 mimics or a scrambled control sequence were examined for miR-205 expressions and mRNA levels of ZEB1, E-cadherin, and α-SMA using real-time qPCR; the protein levels of ZEB1, ZEB2, E-cadherin, and α-SMA were detected with Western blotting. Immunohistochemistry was performed to examine the ectopic expression of β-catenin and E-cadherin expression in the cells...
December 20, 2016: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/27997859/interleukin-1%C3%AE-as-a-driver-of-renal-ngal-production
#11
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/27989596/fascin2-regulates-cisplatin-induced-apoptosis-in-nrk-52e-cells
#12
Xinhui Wang, LaNita Nichols, Elizabeth A Grunz-Borgmann, Zhe Sun, Gerald A Meininger, Timothy L Domeier, Christopher P Baines, Alan R Parrish
Previous studies have shown that the aging kidney has a marked loss of α(E)-catenin in proximal tubular epithelium. α-Catenin, a key regulator of the actin cytoskeleton, interacts with a variety of actin-binding proteins. Cisplatin-induced loss of fascin2, an actin bundling protein, was observed in cells with a stable knockdown of α(E)-catenin (C2 cells), as well as in aging (24 mon), but not young (4 mon), kidney. Fascin2 co-localized with α-catenin and the actin cytoskeleton in NRK-52E cells. Knockdown of fascin2 increased the susceptibility of tubular epithelial cells to cisplatin-induced injury...
January 15, 2017: Toxicology Letters
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
#13
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
#14
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/27927603/lysophosphatidic-acid-signaling-through-its-receptor-initiates-profibrotic-epithelial-cell-fibroblast-communication-mediated-by-epithelial-cell-derived-connective-tissue-growth-factor
#15
Norihiko Sakai, Jerold Chun, Jeremy S Duffield, David Lagares, Takashi Wada, Andrew D Luster, Andrew M Tager
The expansion of the fibroblast pool is a critical step in organ fibrosis, but the mechanisms driving expansion remain to be fully clarified. We previously showed that lysophosphatidic acid (LPA) signaling through its receptor LPA1 expressed on fibroblasts directly induces the recruitment of these cells. Here we tested whether LPA-LPA1 signaling drives fibroblast proliferation and activation during the development of renal fibrosis. LPA1-deficient (LPA1(-/-)) or -sufficient (LPA1(+/+)) mice were crossed to mice with green fluorescent protein expression (GFP) driven by the type I procollagen promoter (Col-GFP) to identify fibroblasts...
December 4, 2016: Kidney International
https://www.readbyqxmd.com/read/27925186/up-regulation-of-transient-receptor-potential-melastatin-6-channel-expression-by-tumor-necrosis-factor-%C3%AE-in-the-presence-of-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor
#16
Chisa Furukawa, Naoko Fujii, Aya Manabe, Toshiyuki Matsunaga, Satoshi Endo, Hajime Hasegawa, Yoshinori Ito, Masahiko Yamaguchi, Yasuhiro Yamazaki, Akira Ikari
Anti-epidermal growth factor receptor (EGFR) drugs such as erlotinib and gefitinib cause a side effect of hypomagnesemia, but chemotherapy to treat this has not yet been developed. The transient receptor potential melastatin 6 (TRPM6) channel is involved in the reabsorption of Mg(2+) in the renal tubule. We reported previously that the expression of TRPM6 is up-regulated by epidermal growth factor (EGF) in renal tubular epithelial NRK-52E and HEK293 cells. EGF-induced elevation of TRPM6 expression was inhibited by erlotinib, gefitinib, and lapatinib...
December 7, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27924516/carbon-monoxide-inhibits-the-nuclear-cytoplasmic-translocation-of-hmgb1-in-an-in-vitro-oxidative-stress-injury-model-of-mouse-renal-tubular-epithelial-cells
#17
Yu Jia, Lu Wang, Guang-Yuan Zhao, Zhi-Qiang Wang, Song Chen, Gang Chen
Carbon monoxide (CO), as a vital small molecule in signaling pathways, is found to be involved in ischemia-reperfusion injury (IRI) in renal transplantation. CO-releasing molecule-2 (CORM-2), a CO-releasing molecule, is a type of metal carbonyl complexes which can quickly release CO in vivo. In this study, an in vitro oxidative stress injury model was established to examine the effect of CORM-2 pretreatment on the nuclear-cytoplasmic translocation of high mobility group box 1 protein (HMGB1) in mouse primary renal proximal tubular epithelial cells (RPTECs)...
December 2016: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/27916883/enhanced-autophagy-in-polycystic-kidneys-of-aqp11-null-mice
#18
Yasuko Tanaka, Mayumi Watari, Tatsuya Saito, Yoshiyuki Morishita, Kenichi Ishibashi
Aquaporin-11 (AQP11) is an intracellular water channel expressed at the endoplasmic reticulum (ER) of the proximal tubule. Its gene disruption in mice leads to intracellular vacuole formation at one week and the subsequent development of polycystic kidneys by three weeks. As the damaged proximal tubular cells with intracellular vacuoles form cysts later, we postulated that autophagy may play a role in the cyst formation and examined autophagy activity before and after cyst development in AQP11(-/-) kidneys...
November 30, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27882940/mdm2-prevents-spontaneous-tubular-epithelial-cell-death-and-acute-kidney-injury
#19
Dana Thomasova, Martrez Ebrahim, Kristina Fleckinger, Moying Li, Jakob Molnar, Bastian Popper, Helen Liapis, Ahmed M Kotb, Florian Siegerist, Nicole Endlich, Hans-Joachim Anders
Murine double minute-2 (MDM2) is an E3-ubiquitin ligase and the main negative regulator of tumor suppressor gene p53. MDM2 has also a non-redundant function as a modulator of NF-kB signaling. As such it promotes proliferation and inflammation. MDM2 is highly expressed in the unchallenged tubular epithelial cells and we hypothesized that MDM2 is necessary for their survival and homeostasis. MDM2 knockdown by siRNA or by genetic depletion resulted in demise of tubular cells in vitro. This phenotype was completely rescued by concomitant knockdown of p53, thus suggesting p53 dependency...
November 24, 2016: Cell Death & Disease
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
#20
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
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