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https://www.readbyqxmd.com/read/28448446/renalase-protects-against-renal-fibrosis-by-inhibiting-the-activation-of-the-erk-signaling-pathways
#1
Yiru Wu, Liyan Wang, Dai Deng, Qidong Zhang, Wenhu Liu
Renal interstitial fibrosis is a common pathway for the progression of chronic kidney disease (CKD) to end-stage renal disease. Renalase, acting as a signaling molecule, has been reported to have cardiovascular and renal protective effects. However, its role in renal fibrosis remains unknown. In this study, we evaluated the therapeutic efficacy of renalase in rats with complete unilateral ureteral obstruction (UUO) and examined the inhibitory effects of renalase on transforming growth factor-β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) in human proximal renal tubular epithelial (HK-2) cells...
April 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28447719/hepatocyte-growth-factor-inhibits-tubular-epithelial%C3%A2-myofibroblast-transdifferentiation-by-suppression-of-angiotensin-ii-via-the-jak2-stat3-signaling-pathway
#2
Hong-Yue Wang, Chen Zhang, Qing-Fei Xiao, Hai-Chuan Dou, Yan Chen, Chun-Mei Gu, Ming-Ji Cui
Tubular epithelial‑myofibroblast transdifferentiation (TEMT) is important in the development of chronic renal failure. The present study investigated whether hepatocyte growth factor (HGF) inhibits TEMT, and whether this function may be associated with the inhibition of angiotensin II (AngII) and the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. Human HK‑2 kidney proximal tubular cells were divided into 4 groups and treated with AngII (1x10‑6 M), HGF (8x10‑3 M), AngII plus HGF or control conditions, followed by an assessment of apoptosis induction and the expression levels of α‑smooth muscle actin (α‑SMA), which is a marker of TEMT...
March 9, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28440499/effects-of-tanshinone-iia-on-the-regulation-of-renal-proximal-tubular-fibrosis
#3
Luoyuan Cao, Baoying Huang, Xianguo Fu, Jing Yang, Yinghua Lin, Feng Lin
The development of diabetes mellitus, along with its complications, is a chronic inflammatory response process. Chronic kidney diseases are characterized by renal fibrosis, and fibrosis is an important pathway for end‑stage renal failure. According to previous studies, high glucose (HG) has been demonstrated to be the most important fibrogenesis‑inducing agent. Tanshinone IIA is one of the main components isolated from Danshen (Salvia miltiorrhiza). Although tanshinone IIA has been widely used for the treatment of cardiovascular diseases, the possible role of tanshinone IIA in fibrosis regulation remains to be elucidated and requires investigation...
April 21, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28424212/pdgf-receptor-%C3%AE-uses-akt-mtorc1-signaling-node-to-promote-high-glucose-induced-renal-proximal-tubular-cell-collagen-i-%C3%AE-2-expression
#4
Falguni Das, Nandini Ghosh-Choudhury, Balachandar Venkatesan, Balakuntalam S Kasinath, Goutam Ghosh Choudhury
Increased expression of PDGF receptor-β (PDGFRβ) has been shown in the diabetic renal proximal tubules. The core molecular network used by high glucose to induce proximal tubular epithelial cell collagen I (α2) expression is poorly understood. We hypothesized that activation of PDGFRβ by high glucose increases collagen I (α2) production via Akt/mTORC1 signaling pathway in proximal tubular epithelial cells. Using biochemical and molecular biological techniques, we investigated this hypothesis. We show that high glucose increases activating phosphorylation of the PDGFRβ, resulting in the phosphorylation of the phosphatidylinositol 3 kinase...
April 19, 2017: American Journal of Physiology. Renal Physiology
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/28417340/preconditioning-of-primary-human-renal-proximal-tubular-epithelial-cells-without-tryptophan-increases-survival-under-hypoxia-by-inducing-autophagy
#7
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
#8
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...
March 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28405545/maslinic-acid-inhibits-proliferation-of-renal-cell-carcinoma-cell-lines-and-suppresses-angiogenesis-of-endothelial-cells
#9
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/28404591/intravital-imaging-of-the-kidney-in-a-rat-model-of-salt-sensitive-hypertension
#10
Bradley T Endres, Ruben M Sandoval, George J Rhodes, Silvia B Campos-Bilderback, Malgorzata M Kamocka, Christopher McDermott-Roe, Alexander Staruschenko, Bruce A Molitoris, Aron M Geurts, Oleg Palygin
Hypertension is one of the most prevalent diseases worldwide, and a major risk factor for renal failure and cardiovascular disease. The role of albuminuria, a common feature of hypertension and robust predictor of cardiorenal disorders, remains incompletely understood. The goal of this study was to investigate the mechanisms leading to albuminuria in the kidney of a rat model of hypertension, the Dahl salt-sensitive (SS) rat. To determine the relative contributions of the glomerulus and proximal tubule (PT) to albuminuria, we applied intravital two-photon-based imaging to investigate the complex renal physiological changes that occur during salt-induced hypertension...
April 12, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28399045/a-differential-expression-of-uncoupling-protein-2-associates-with-renal-damage-in-stroke-resistant-spontaneously-hypertensive-rat-stroke-prone-spontaneously-hypertensive-rat-derived-stroke-congenic-lines
#11
Speranza Rubattu, Maria Cotugno, Franca Bianchi, Luigi Sironi, Paolo Gelosa, Rosita Stanzione, Maurizio Forte, Claudia De Sanctis, Michele Madonna, Simona Marchitti, Alice Pignieri, Sebastiano Sciarretta, Massimo Volpe
OBJECTIVES: Uncoupling protein-2 (UCP2), a mitochondrial anion transporter involved in mitochondrial uncoupling, limiting reactive oxygen species formation, is significantly downregulated in kidneys of high-salt-fed stroke-prone spontaneously hypertensive rat (SHRSP), where it associates with increased renal damage occurrence. METHODS: We aimed at establishing whether UCP2 differential expression associates with renal damage in two stroke-resistant spontaneously hypertensive rat (SHRSR)/SHRSP-derived stroke congenic lines...
April 10, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28387228/calcium-oxalate-crystals-and-oxalate-induce-an-epithelial-to-mesenchymal-transition-in-the-proximal-tubular-epithelial-cells-contribution-to-oxalate-kidney-injury
#12
Marcia Bastos Convento, Edson Andrade Pessoa, Edgar Cruz, Maria Aparecida da Glória, Nestor Schor, Fernanda Teixeira Borges
TGF-β1 is the main mediator of epithelial-to-mesenchymal transition (EMT). Hyperoxaluria induces crystalluria, interstitial fibrosis, and progressive renal failure. This study analyzed whether hyperoxaluria is associated with TGF-β1 production and kidney fibrosis in mice and if oxalate or calcium oxalate (CaOx) could induce EMT in proximal tubule cells (HK2) and therefore contribute to the fibrotic process. Hyperoxaluria was induced by adding hydroxyproline and ethylene glycol to the mice's drinking water for up to 60 days...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28386751/relaxin-attenuates-aristolochic-acid-induced-human-tubular-epithelial-cell-apoptosis-in-vitro-by-activation-of-the-pi3k-akt-signaling-pathway
#13
Xiang-Cheng Xie, Ning Zhao, Qun-Hong Xu, Xiu Yang, Wen-Kai Xia, Qi Chen, Ming Wang, Xiao Fei
Aristolochic acid nephropathy remains a leading cause of chronic kidney disease (CKD), however few treatment strategies exist. Emerging evidence has shown that H2 relaxin (RLX) possesses powerful antifibrosis and anti-apoptotic properties, therefore we aimed to investigate whether H2 relaxin can be employed to reduce AA-induced cell apoptosis. Human proximal tubular epithelial (HK-2) cells exposed to AA-I were treated with or without administration of H2 RLX. Cell viability was examined using the WST-8 assay...
June 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28381520/melamine-induces-ca-2-sensing-receptor-activation-and-elicits-apoptosis-in-proximal-tubular-cells
#14
Allen J Yiu, Cliff-Lawrence Ibeh, Sanjit K Roy, Bidhan C Bandyopadhyay
Melamine causes renal tubular cell injury through inflammation, fibrosis and apoptosis. While melamine effects the rise in intracellular Ca(2+) concentration ([Ca(2+)]i), reactive oxygen species (ROS) production, and pro-apoptotic pathway activation, the mechanism of upstream Ca(2+) signaling is unknown. Since melamine has some structural similarities with L-amino acids, which endogenously activates Ca(2+)-sensing receptors (CSR), we examined the effect of melamine on CSR-induced Ca(2+) signaling and apoptotic cell death...
April 5, 2017: American Journal of Physiology. Cell Physiology
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
#15
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 accompanies epithelial repair, but also participates into kidney fibrosis, histological substratum of CKD...
March 30, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28361304/parietal-cells-new-perspectives-in-glomerular-disease
#16
Laura Miesen, Eric Steenbergen, Bart Smeets
In normal glomeruli, parietal epithelial cells (PECs) line the inside of Bowman's capsule and form an inconspicuous sheet of flat epithelial cells in continuity with the proximal tubular epithelial cells (PTECs) at the urinary pole and with the podocytes at the vascular pole. PECs, PTECs and podocytes have a common mesenchymal origin and are the result of divergent differentiation during embryogenesis. Podocytes and PTECs are highly differentiated cells with well-established functions pertaining to the maintenance of the filtration barrier and transport, respectively...
March 30, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28350099/small-heterodimer-partner-attenuates-hydrogen-peroxide-induced-expression-of-cyclooxygenase-2-and-inducible-nitric-oxide-synthase-by-suppression-of-activator-protein-1-and-nuclear-factor-%C3%AE%C2%BAb-in-renal-proximal-tubule-epithelial-cells
#17
Jung Sun Park, Hoon In Choi, Eun Hui Bae, Seong Kwon Ma, Soo Wan Kim
The orphan nuclear receptor, small heterodimer partner (SHP), plays a negative regulatory role in innate immune responses and is involved in various inflammatory signaling pathways. In the present study, we aimed to ascertain whether SHP is effective in preventing hydrogen peroxide (H2O2)-induced kidney tubular inflammation and explored the molecular mechanisms underlying the protective effects of SHP. Renal ischemia/reperfusion (I/R) injury was induced in mice by clamping both renal pedicles for 30 min...
February 9, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28333068/effects-of-reactive-oxygen-species-on-tubular-transport-along-the-nephron
#18
REVIEW
Agustin Gonzalez-Vicente, Jeffrey L Garvin
Reactive oxygen species (ROS) are oxygen-containing molecules naturally occurring in both inorganic and biological chemical systems. Due to their high reactivity and potentially damaging effects to biomolecules, cells express a battery of enzymes to rapidly metabolize them to innocuous intermediaries. Initially, ROS were considered by biologists as dangerous byproducts of respiration capable of causing oxidative stress, a condition in which overproduction of ROS leads to a reduction in protective molecules and enzymes and consequent damage to lipids, proteins, and DNA...
March 23, 2017: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/28331061/an-intracellular-matrix-metalloproteinase-2-isoform-induces-tubular-regulated-necrosis-implications-for-acute-kidney-injury
#19
Carla S Ceron, Celine Baligand, Sunil K Joshi, Shaynah Wanga, Patrick M Cowley, Joy P Walker, Sang Heon Song, Rajeev Mahimkar, Anthony J Baker, Robert L Raffai, Zhen J Wang, David H Lovett
Acute kidney injury (AKI) causes severe morbidity, mortality, and chronic kidney disease (CKD). Mortality is particularly marked in the elderly and with pre-existing CKD. Oxidative stress is a common theme in models of AKI induced by ischemia/reperfusion (I/R) injury. We recently characterized an intracellular isoform of matrix metalloproteinase-2 (MMP-2) induced by oxidative stress-mediated activation of an alternate promoter in the first intron of the MMP-2 gene. This generates an N-terminal truncated MMP-2 isoform (NTT-MMP-2) that is intracellular and associated with mitochondria...
March 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28331059/adaptive-changes-in-gfr-tubular-morphology-and-transport-in-subtotal-nephrectomized-kidneys-modeling-and-analysis
#20
Anita T Layton, Aurélie Edwards, Volker Vallon
Removal of renal mass stimulates anatomical and functional adaptations in the surviving nephrons, including elevation in single-nephron glomerular filtration rate (SNGFR) and tubular hypertrophy. A goal of this study is to assess the extent to which the concomitant increases in filtered load and tubular transport capacity preserve homeostasis of water and salt. To accomplish that goal, we developed computational models to simulate solute transport and metabolism along nephron populations in a uninephrectomized (UNX) rat and a 5/6-nephrectomized (5/6-NX) rat...
March 22, 2017: American Journal of Physiology. Renal Physiology
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