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https://www.readbyqxmd.com/read/28523000/mast-cells-and-mcpt4-chymase-promote-renal-impairment-after-partial-ureteral-obstruction
#1
Maguelonne Pons, Liza Ali, Walid Beghdadi, Luca Danelli, Marianne Alison, Lydia Celia Madjène, Jessica Calvo, Julien Claver, Shamila Vibhushan, Magnus Åbrink, Gunnar Pejler, Marie-Laurence Poli-Mérol, Michel Peuchmaur, Alaa El Ghoneimi, Ulrich Blank
Obstructive nephropathy constitutes a major cause of pediatric renal progressive disease. The mechanisms leading to disease progression are still poorly understood. Kidney fibrotic lesions are reproduced using a model of partial unilateral ureteral obstruction (pUUO) in newborn mice. Based on data showing significant mast cell (MC) infiltration in patients, we investigated the role of MC and murine MCPT4, a MC-released chymase, in pUUO using MC- (W(sh/sh)), MCPT4-deficient (Mcpt4(-/-)), and wild-type (WT) mice...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28473886/unique-molecular-profile-of-exosomes-derived-from-primary-human-proximal-tubular-epithelial-cells-under-diseased-conditions
#2
Xiangju Wang, Ray Wilkinson, Katrina Kildey, Jeremy Potriquet, Jason Mulvenna, Richard J Lobb, Andreas Möller, Nicole Cloonan, Pamela Mukhopadhyay, Andrew J Kassianos, Helen Healy
Human proximal tubular epithelial cells (PTEC) of the kidney are known to respond to and mediate the disease process in a wide range of kidney diseases, yet their exosomal production and exosome molecular cargo remain a mystery. Here we investigate, for the first time, the production and molecular content of exosomes derived from primary human PTEC cultured under normal and diseased conditions representing a spectrum of in vivo disease severity from early inflammation, experienced in multiple initial kidney disease states, through to hypoxia, frequently seen in late stage chronic kidney disease (CKD) due to fibrosis and vascular compromise...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28468965/cell-specific-qrt-pcr-of-renal-epithelial-cells-reveals-a-novel-innate-immune-signature-in-murine-collecting-duct
#3
Vijay Saxena, David S Hains, John Ketz, Melinda Chanley, John D Spencer, Brian Becknell, Keith R Pierce, Raoul D Nelson, Jeffrey M Purkerson, George J Schwartz, Andrew L Schwaderer
The urinary tract is usually culture negative despite its close proximity to microbial flora. The precise mechanisms by which the kidneys and urinary tract defends against infection is not well understood. The initial kidney cells to encounter ascending pathogens are the collecting tubule cells which consist of principal cells (PCs) that express aquaporin 2 (AQP2) and intercalated cells (ICs) that express vacuolar H+-ATPase (V-ATPase, B1 subunit). We have previously shown that ICs are involved with the human renal innate immune defense...
May 3, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28428545/beclin-1-mediated-autophagy-protects-against-cadmium-activated-apoptosis-via-the-fas-fasl-pathway-in-primary-rat-proximal-tubular-cell-culture
#4
Gang Liu, Yan Yuan, Mengfei Long, Tongwang Luo, Jianchun Bian, Xuezhong Liu, Jianhong Gu, Hui Zou, Ruilong Song, Yi Wang, Lin Wang, Zongping Liu
The Fas/FasL signaling pathway is one of the primary apoptosis pathways, but the involvement and regulatory mechanism of this pathway by autophagy remain unclear. Here we demonstrated that cadmium (Cd) activated the Fas/FasL apoptosis pathway in rat proximal tubular (rPT) cells; this was accompanied by simultaneous activation of autophagy resulted in reduced apoptosis. In this model, we induced autophagy through RAPA and further demonstrated that autophagy protects against activation of Fas/FasL signaling and apoptosis...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28423497/drp1-dependent-mitophagy-protects-against-cisplatin-induced-apoptosis-of-renal-tubular-epithelial-cells-by-improving-mitochondrial-function
#5
Chuanyan Zhao, Zhuyun Chen, Jia Qi, Suyan Duan, Zhimin Huang, Chengning Zhang, Lin Wu, Ming Zeng, Bo Zhang, Ningning Wang, Huijuan Mao, Aihua Zhang, Changying Xing, Yanggang Yuan
Cisplatin chemotherapy often causes acute kidney injury (AKI) in cancer patients. There is increasing evidence that mitochondrial dysfunction plays an important role in cisplatin-induced nephrotoxicity. Degradation of damaged mitochondria is carried out by mitophagy. Although mitophagy is considered of particular importance in protecting against AKI, little is known of the precise role of mitophagy and its molecular mechanisms during cisplatin-induced nephrotoxicity. Also, evidence that activation of mitophagy improved mitochondrial function is lacking...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420760/novel-lnc-rna-regulated-by-hif-1-inhibits-apoptotic-cell-death-in-the-renal-tubular-epithelial-cells-under-hypoxia
#6
Imari Mimura, Yosuke Hirakawa, Yasuharu Kanki, Natsuki Kushida, Ryo Nakaki, Yutaka Suzuki, Tetsuhiro Tanaka, Hiroyuki Aburatani, Masaomi Nangaku
Chronic tubulointerstitial hypoxia plays an important role as the final common pathway to end-stage renal disease. HIF-1 (hypoxia-inducible factor-1) is a master transcriptional factor under hypoxia, regulating downstream target genes. Genome-wide analysis of HIF-1 binding sites using high-throughput sequencers has clarified various kinds of downstream targets and made it possible to demonstrate the novel roles of HIF-1. Our aim of this study is to identify novel HIF-1 downstream epigenetic targets which may play important roles in the kidney...
April 2017: Physiological Reports
https://www.readbyqxmd.com/read/28419922/cadmium-induces-ca-2-mediated-calpain-1-caspase-3-dependent-apoptosis-in-primary-cultured-rat-proximal-tubular-cells
#7
Hong Wang, Nianhui Zhai, Ying Chen, Haibin Xu, Kehe Huang
Calcium, as a ubiquitous second messenger, governs a large array of cellular processes and is necessary for cell survival. More recently, it was observed that the cytosolic Ca(2+) concentration ([Ca(2+)]c) elevation could induce apoptosis in primary cultured rat proximal tubular (rPT) cells exposed to cadmium (Cd), but the concrete mechanism is still unclear. This study was designed to investigate the signal pathway involved in [Ca(2+)]c elevation-mediated apoptosis. The results confirmed the elevation of [Ca(2+)]c by confocal microscopy and enhancement of the apoptosis by Hoechst 33258 staining and flow cytometer when rPT cells were exposed to Cd for 12h...
April 8, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28417340/preconditioning-of-primary-human-renal-proximal-tubular-epithelial-cells-without-tryptophan-increases-survival-under-hypoxia-by-inducing-autophagy
#8
Theodoros Eleftheriadis, Georgios Pissas, Maria Sounidaki, Nikolaos Antoniadis, Georgia Antoniadi, Vassilios Liakopoulos, Ioannis Stefanidis
PURPOSE: Hypoxia plays a significant role in the pathogenesis of acute kidney injury (AKI). Autophagy protects from AKI. Amino acid deprivation induces autophagy. The effect of L-tryptophan depletion on survival and autophagy in cultures of renal proximal tubular epithelial cells (RPTECs) under hypoxia was evaluated. METHODS: RPTECs were preconditioned in a medium containing or not tryptophan, following culture under hypoxia and treatment with or without the autophagy inhibitor chloroquine...
April 17, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28415724/pharmacological-inhibition-of-src-kinase-protects-against-acute-kidney-injury-in-a-murine-model-of-renal-ischemia-reperfusion
#9
Chongxiang Xiong, Xiujuan Zang, Xiaoxu Zhou, Lirong Liu, Monica V Masucci, Jinhua Tang, Xuezhu Li, Na Liu, George Bayliss, Ting C Zhao, Shougang Zhuang
Activation of Src kinase has been implicated in the pathogenesis of acute brain, liver, and lung injury. However, the role of Src in acute kidney injury (AKI) remains unestablished. To address this, we evaluated the effects of Src inhibition on renal dysfunction and pathological changes in a murine model of AKI induced by ischemia/reperfusion (I/R). I/R injury to the kidney resulted in increased Src phosphorylation at tyrosine 416 (activation). Administration of PP1, a highly selective Src inhibitor, blocked Src phosphorylation, improved renal function and ameliorated renal pathological damage...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28405545/maslinic-acid-inhibits-proliferation-of-renal-cell-carcinoma-cell-lines-and-suppresses-angiogenesis-of-endothelial-cells
#10
Parth Thakor, Wenzhe Song, Ramalingam B Subramanian, Vasudev R Thakkar, David A Vesey, Glenda C Gobe
Despite the introduction of many novel therapeutics in clinical practice, metastatic renal cell carcinoma (RCC) remains a treatment-resistant cancer. As red and processed meat are considered risk factors for RCC, and a vegetable-rich diet is thought to reduce this risk, research into plant-based therapeutics may provide valuable complementary or alternative therapeutics for the management of RCC. Herein, we present the antiproliferative and antiangiogenic effects of maslinic acid, which occurs naturally in edible plants, particularly in olive fruits, and also in a variety of medicinal plants...
2017: Journal of Kidney Cancer and VHL
https://www.readbyqxmd.com/read/28366875/dual-role-of-muc1-mucin-in-kidney-ischemia-reperfusion-injury-nephroprotector-in-early-phase-but-pro-fibrotic-in-late-phase
#11
Jean-Baptiste Gibier, Brigitte Hémon, Mélanie Fanchon, Kelly Gaudelot, Nicolas Pottier, Bélinda Ringot, Isabelle Van Seuningen, François Glowacki, Christelle Cauffiez, David Blum, Marie-Christine Copin, Michaël Perrais, Viviane Gnemmi
Acute kidney injury (AKI) is characterized by acute tubular necrosis (ATN) which involves mainly proximal tubules. Past AKI is associated with higher risk of chronic kidney disease (CKD). The MUC1 mucin is a large glycoprotein responsible for epithelial protection and locates to convoluted distal tubules and collecting ducts. Since MUC1 activates the epithelial-mesenchymal transition (EMT) in carcinoma cells, we hypothesized that MUC1 could be involved in epithelial tubular cell plasticity, a process that not only accompanies epithelial repair, but also participates into kidney fibrosis, histological substratum of CKD...
March 31, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28323095/megalin-targeted-enhanced-transfection-efficiency-in-cultured-human-hk-2-renal-tubular-proximal-cells-using-aminoglycoside-carboxyalkyl-polyethylenimine-containing-nanoplexes
#12
Fatemeh Oroojalian, Ali Hossein Rezayan, Wayne Thomas Shier, Khalil Abnous, Mohammad Ramezani
Non-viral vectors are of interest as therapeutic gene delivery agents in gene therapy, because they are simple to prepare, easy to modify and have definable safety profiles compared to viral vectors. The potential of gene therapy in the treatment of renal diseases is limited by a lack of effective kidney-targeted gene delivery systems. Aminoglycoside antibiotics gentamicin and neomycin were connected by amide linkages to carboxyl groups on carboxyalkylated-PEI25 (25kDa PEI) or carboxyalkylated-PEI10 (10kDa PEI)...
March 16, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28302075/renal-effects-of-metallothionein-induction-by-zinc-in-vitro-and-in-vivo
#13
Moritz Schanz, Lea Schaaf, Juergen Dippon, Dagmar Biegger, Peter Fritz, Mark Dominik Alscher, Martin Kimmel
BACKGROUND: Metallothionein (MTT) is an endogenous antioxidant that can be induced by both zinc (Zn) and ischemia. In kidneys, increased MTT expression exerts a putative protective role in diabetes and hypoxia. Our goal was to further investigate the behavior of MTT under the influence of Zn and hypoxia in vitro and in vivo. METHODS: MTT expression was measured in vitro in cell cultures of proximal tubular cells (LCC-PK1) by immune-histochemistry and real-time PCR after incubation with increasing concentrations of Zn under hypoxic and non-hypoxic conditions...
March 16, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28246295/autophagy-inhibits-the-accumulation-of-advanced-glycation-end-products-by-promoting-lysosomal-biogenesis-and-function-in-the-kidney-proximal-tubules
#14
Atsushi Takahashi, Yoshitsugu Takabatake, Tomonori Kimura, Ikuko Maejima, Tomoko Namba, Takeshi Yamamoto, Jun Matsuda, Satoshi Minami, Jun-Ya Kaimori, Isao Matsui, Taiji Matsusaka, Fumio Niimura, Tamotsu Yoshimori, Yoshitaka Isaka
Advanced glycation end products (AGEs) are involved in the progression of diabetic nephropathy. AGEs filtered by glomeruli or delivered from the circulation are endocytosed and degraded in the lysosomes of kidney proximal tubular epithelial cells (PTECs). Autophagy is a highly conserved degradation system which regulates intracellular homeostasis by engulfing cytoplasmic components. We have recently demonstrated that autophagic degradation of damaged lysosomes is indispensable for cellular homeostasis in some settings...
February 28, 2017: Diabetes
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
#15
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...
April 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
#16
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
#17
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...
April 1, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28139717/deferasirox-induced-iron-depletion-promotes-bclxl-downregulation-and-death-of-proximal-tubular-cells
#18
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
#19
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
#20
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
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