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https://www.readbyqxmd.com/read/28811645/inhibin-a-and-decorin-secreted-by-human-adult-renal-stem-progenitor-cells-through-the-tlr2-engagement-induce-renal-tubular-cell-regeneration
#1
Fabio Sallustio, Claudia Curci, Alessandra Aloisi, Chiara Cristina Toma, Elisabetta Marulli, Grazia Serino, Sharon Natasha Cox, Giuseppe De Palma, Alessandra Stasi, Chiara Divella, Rosaria Rinaldi, Francesco Paolo Schena
Acute kidney injury (AKI) is a public health problem worldwide. Several therapeutic strategies have been made to accelerate recovery and improve renal survival. Recent studies have shown that human adult renal progenitor cells (ARPCs) participate in kidney repair processes, and may be used as a possible treatment to promote regeneration in acute kidney injury. Here, we show that human tubular ARPCs (tARPCs) protect physically injured or chemically damaged renal proximal tubular epithelial cells (RPTECs) by preventing cisplatin-induced apoptosis and enhancing proliferation of survived cells...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28790310/p16-ink4a-deletion-ameliorated-renal-tubulointerstitial-injury-in-a-stress-induced-premature-senescence-model-of-bmi-1-deficiency
#2
Jianliang Jin, Jianguo Tao, Xin Gu, Zhenzhen Yu, Rong Wang, Guoping Zuo, Qing Li, Xianhui Lv, Dengshun Miao
To determine whether p16 (INK4a) deletion ameliorated renal tubulointerstitial injury by inhibiting a senescence-associated secretory phenotype (SASP) in Bmi-1-deficient (Bmi-1 (-/-)) mice, renal phenotypes were compared among 5-week-old Bmi-1 and p16 (INK4a) double-knockout, and Bmi-1 (-/-) and wild-type mice. Fifth-passage renal interstitial fibroblasts (RIFs) from the three groups were analyzed for senescence and proliferation. The effect of Bmi-1 deficiency on epithelial-to-mesenchymal transition (EMT) was examined in Bmi-1-knockdown human renal proximal tubular epithelial (HK2) cells, which were treated with concentrated conditioned medium (CM) from the fifth-passage renal interstitial fibroblasts (RIFs) of above three group mice or with exogenous TGF-β1...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28775336/shape-dependent-cellular-toxicity-on-renal-epithelial-cells-and-stone-risk-of-calcium-oxalate-dihydrate-crystals
#3
Xin-Yuan Sun, Jian-Ming Ouyang, Kai Yu
Renal epithelial cell injury causes crystal retention and leads to renal stone formation. However, the effects of crystal shape on cell injury and stone risk remain unclear. This study compared the cytotoxicity degrees of calcium oxalate dihydrate (COD) crystals having different shapes toward human kidney proximal tubular epithelial (HK-2) cells to reveal the effect of crystal shape on cell injury and to elucidate the pathological mechanism of calcium oxalate kidney stones. The effects of exposure to cross-shaped (COD-CS), flower-like (COD-FL), bipyramid (COD-BD), and elongated-bipyramid (COD-EBD) COD crystals on HK-2 cells were investigated by examining the cell viability, cell membrane integrity, cell morphology change, intracellular reactive oxygen species, mitochondrial membrane potential (Δψm), and apoptotic and/or necrotic rate...
August 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28767410/orellanine-specifically-targets-renal-clear-cell-carcinoma
#4
Lisa Buvall, Heidi Hedman, Alina Khramova, Deman Najar, Lovisa Bergwall, Kerstin Ebefors, Carina Sihlbom, Sven Lundstam, Anders Herrmann, Hanna Wallentin, Emelie Roos, Ulf A Nilsson, Martin Johansson, Jan Törnell, Börje Haraldsson, Jenny Nyström
Renal cell carcinoma (RCC), arising from the proximal tubule in the kidney, accounts for approximately 85% of kidney cancers and causes over 140,000 annual deaths worldwide. In the last decade, several new therapies have been identified for treatment of metastatic RCC. Although these therapies increase survival time compared to standard care, none of them has curative properties. The nephrotoxin orellanine specifically targets proximal tubular epithelial cells, leaving other organs unaffected. We therefore hypothesized that the selective toxicity of orellanine extends to clear cell RCC (ccRCC) cells since they emanate from proximal tubular cells...
July 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28760545/reactive-carbonyl-compounds-impair-wound-healing-by-vimentin-collapse-and-loss-of-the-primary-cilium
#5
Lara Rodríguez-Ribera, Craig Slattery, Tara Mc Morrow, Ricard Marcos, Susana Pastor
In renal pathologies tubulo-interstitial fibrosis results from an aberrant wound-healing ability where the normal epithelial tissue is substituted for scar tissue caused by accumulation of extracellular matrix proteins (ECM). During the wound-healing process, epithelial cells may undergo epithelial-mesenchymal transition (EMT) acquiring a mesenchymal-like phenotype that allows cells to migrate and re-epithelialize the wound site. It has been reported that chronic inflammation and uremic milieu are involved in wound-healing and enhanced kidney damage in chronic kidney disease (CKD) patients...
July 29, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28748873/apoptosis-of-rat-renal-cells-by-organophosphate-pesticide-quinalphos-ultrastructural-study
#6
Refaat A Eid
Quinalphos or Ekalux, an organophosphate pesticide, is used in controlling the pests of a variety of crops. Quinalphos was studied on male Sprague-Dawley albino rats. The acute po LD50 of technical Ekalux was 19.95 mg/kg in males. Ekalux, produced several pathological changes in the kidney. A glomerulus demonstrated capillary lumina occluded by degenerated cellular debris. Basement membrane showed irregular wrinkling and branching. The proximal tubular cells showed damage such as dilation of endoplasmic reticulum, accumulation of glycogen granules, and pyknotic nucleus...
July 2017: Saudi Journal of Kidney Diseases and Transplantation
https://www.readbyqxmd.com/read/28744711/calcitriol-ameliorates-angiotensinii-induced-renal-injury-partly-via-upregulating-a20
#7
Hongfei Zhao, Yunfeng Xia, Hua Gan
Inflammation and reactive oxygen species (ROS) play crucial roles in the progression of chronic kidney diseases. Vitamin D has been shown anti-inflammatory effects, but the underlying mechanism is not fully understood. Here, we investigated whether calcitriol exerts protective effects via upregulating A20 in angiotensinII (AngII)-induced renal injury. Male C57BL/6 mice were infused with vehicle or AngII for 10 days. Calcitriol reduced infiltration of T lymphocytes and macrophages. This reduction of inflammatory cells was accompanied by elevated A20 and decreased pro-inflammatory cytokines (PICs) and reactive oxygen species (ROS)...
July 25, 2017: Inflammation
https://www.readbyqxmd.com/read/28741985/the-influence-of-fasudil-on-renal-proximal-tubular-cell-epithelial-mesenchymal-transition-induced-by-parathormone
#8
Ziqing Gao, Weiping Zhu, Hua Zhang, Zhonghe Li, Tongxia Cui
BACKGROUND: Renal fibrosis is a common pathway through which a variety of chronic kidney diseases progress to end-stage renal disease. Epithelial-mesenchymal transition (EMT) of renal proximal tubular cells is one of the most important factors in renal fibrosis. This study investigates if fasudil could influence EMT of renal proximal tubular cells. METHODS: HK-2 cells in passage 3-4 were used for all experiments. The cells were divided into five groups and treated with different concentrations of PTH and then observe cellular morphological changes at 0, 24 and 48 h using an inverted microscope and investigate the expression of the epithelial cell marker E-cadherin and the renal fibroblast marker α-smooth muscle actin (α-SMA)...
November 2017: Renal Failure
https://www.readbyqxmd.com/read/28739648/hepatocyte-nuclear-factor-1%C3%AE-controls-mitochondrial-respiration-in-renal-tubular-cells
#9
Audrey Casemayou, Audren Fournel, Alessia Bagattin, Joost Schanstra, Julie Belliere, Stéphane Decramer, Dimitri Marsal, Marion Gillet, Nicolas Chassaing, Antoine Huart, Marco Pontoglio, Claude Knauf, Jean-Loup Bascands, Dominique Chauveau, Stanislas Faguer
AKI is a frequent condition that involves renal microcirculation impairment, infiltration of inflammatory cells with local production of proinflammatory cytokines, and subsequent epithelial disorders and mitochondrial dysfunction. Peroxisome proliferator-activated receptor γ coactivator 1-α (PPARGC1A), a coactivator of the transcription factor PPAR-γ that controls mitochondrial biogenesis and function, has a pivotal role in the early dysfunction of the proximal tubule and the subsequent renal repair. Here, we evaluated the potential role of hepatocyte nuclear factor-1β (HNF-1β) in regulating PPARGC1A expression in AKI...
July 24, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28724612/regulation-of-pdz-domain-containing-1-pdzk1-expression-by-hepatocyte-nuclear-factor-1-alpha-hnf1%C3%AE-in-human-kidney
#10
Katharina Prestin, Janine Hussner, Celio Ferreira, Isabell Seibert, Vivien Breitung, Uwe Zimmermann, Henriette Elisabeth Meyer Zu Schwabedissen
In the renal proximal tubule the secretion and reabsorption of glomerularly filtrated compounds is realized by a functional network of uptake and efflux transporters. The activity and localization of several transporters expressed at the apical tubular membrane is regulated by the membrane associated protein PDZ domain containing 1 (PDZK1). We aimed to characterize the transcriptional regulation of this modulator of renal transport. Coexpression analyses of PDZK1 and putative regulators were performed using human kidney samples...
July 19, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28715434/engineered-extracellular-matrices-with-controlled-mechanics-modulate-renal-proximal-tubular-cell-epithelialization
#11
Jeffrey A Beamish, Evan Chen, Andrew J Putnam
Acute kidney injury (AKI) is common and associated with significant morbidity and mortality. Recovery from many forms of AKI involves the proliferation of renal proximal tubular epithelial cells (RPTECs), but the influence of the microenvironment in which this recovery occurs remains poorly understood. Here we report the development of a poly(ethylene glycol) (PEG) hydrogel platform to study the influence of substrate mechanical properties on the proliferation of human RPTECs as a model for recovery from AKI...
2017: PloS One
https://www.readbyqxmd.com/read/28710020/nrf2-deficiency-exacerbates-ochratoxin-a-induced-toxicity-in-vitro-and-in-vivo
#12
Agnieszka Loboda, Anna Stachurska, Mateusz Sobczak, Paulina Podkalicka, Olga Mucha, Alicja Jozkowicz, Jozef Dulak
Several mechanisms are postulated to be responsible for nephrotoxic and nephrocarcinogenic activities of mycotoxin and food contaminant, ochratoxin A (OTA). Although Nrf2 transcription factor was suggested to be involved in OTA-mediated renal injury, comprehensive study evaluating the effect of OTA toxicity in Nrf2 knock-out mice with special regard to sex-dependency has not been performed yet. Our results clearly show exacerbated OTA toxicity in porcine tubular epithelial cells after shRNA-mediated Nrf2 inhibition as well as in proximal tubular cells isolated from Nrf2(-/-) male mice in comparison to cells derived from their wild-type counterparts...
July 12, 2017: Toxicology
https://www.readbyqxmd.com/read/28709637/tubulointerstitial-fibrosis-can-sensitize-the-kidney-to-subsequent-glomerular-injury
#13
Beom Jin Lim, Jae Won Yang, Jun Zou, Jianyong Zhong, Taiji Matsusaka, Ira Pastan, Ming-Zhi Zhang, Raymond C Harris, Hai-Chun Yang, Agnes B Fogo
Chronic glomerular injury is associated with eventual development of tubulointerstitial fibrosis. Here we aimed to assess whether, and how, mild chronic tubulointerstitial injury affects glomeruli. For this, we generated mice expressing different toxin receptors, one on their proximal tubular epithelial cells (diphtheria toxin receptor [DTR]) and the other only on podocytes (human CD25 [IL-2R] driven by the nephrin promoter [Nep25]), allowing serial induction of tubule-specific and glomerular (podocyte)-specific injury, respectively...
July 12, 2017: Kidney International
https://www.readbyqxmd.com/read/28705935/forkhead-box-o3-foxo3-regulates-kidney-tubular-autophagy-following-urinary-tract-obstruction
#14
Ling Li, Ronald Zviti, Catherine Ha, Zhao V Wang, Joseph A Hill, Fangming Lin
Autophagy has been shown to be important for normal homeostasis and adaptation to stress in the kidney. Yet, the molecular mechanisms regulating renal epithelial autophagy are not fully understood. Here, we explored the role of the stress-responsive transcription factor forkhead box O3 (FoxO3) in mediating injury-induced proximal tubular autophagy in mice with unilateral ureteral obstruction (UUO). We show that following UUO, FoxO3 is activated and displays nuclear expression in the hypoxic proximal tubules exhibiting high levels of autophagy...
July 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28701862/protective-effect-of-ginsenosides-rk3-and-rh4-on-cisplatin-induced-acute-kidney-injury-in%C3%A2-vitro-and-in%C3%A2-vivo
#15
Seung-Hoon Baek, Byong-Kyu Shin, Nam Jae Kim, Sun-Young Chang, Jeong Hill Park
BACKGROUND: Nephrotoxicity is the major side effect in cisplatin chemotherapy. Previously, we reported that the ginsenosides Rk3 and Rh4 reduced cisplatin toxicity on porcine renal proximal epithelial tubular cells (LLC-PK1). Here, we aimed to evaluate the protective effect of ginsenosides Rk3 and Rh4 on kidney function and elucidate their antioxidant effect using in vitro and in vivo models of cisplatin-induced acute renal failure. METHODS: An enriched mixture of ginsenosides Rk3 and Rh4 (KG-KH; 49...
July 2017: Journal of Ginseng Research
https://www.readbyqxmd.com/read/28701516/blocking-tgf-%C3%AE-and-%C3%AE-catenin-epithelial-crosstalk-exacerbates-ckd
#16
Stellor Nlandu-Khodo, Surekha Neelisetty, Melanie Phillips, Marika Manolopoulou, Gautam Bhave, Lauren May, Peter E Clark, Haichun Yang, Agnes B Fogo, Raymond C Harris, M Mark Taketo, Ethan Lee, Leslie S Gewin
The TGF-β and Wnt/β-catenin pathways have important roles in modulating CKD, but how these growth factors affect the epithelial response to CKD is not well studied. TGF-β has strong profibrotic effects, but this pleiotropic factor has many different cellular effects depending on the target cell type. To investigate how TGF-β signaling in the proximal tubule, a key target and mediator of CKD, alters the response to CKD, we injured mice lacking the TGF-β type 2 receptor specifically in this epithelial segment...
July 12, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28701356/reciprocal-expression-of-mir-214-and-pten-by-high-glucose-regulates-glomerular-mesangial-and-proximal-tubular-epithelial-cell-hypertrophy-and-matrix-expansion
#17
Amit Bera, Falguni Das, Nandini Ghosh-Choudhury, Meenalakshmi M Mariappan, Balakuntalam S Kasinath, Goutam Ghosh Choudhury
Aberrant expression of microRNAs (miRs) contributes to diabetic renal complications including renal hypertrophy and matrix protein accumulation. Reduced expression of PTEN by hyperglycemia contributes to these processes. We considered involvement of microRNA in the downregulation of PTEN. In the renal cortex of type 1 diabetic mice, we detected increased expression of miR-214 in association with decreased levels of PTEN and, enhanced Akt phosphorylation and fibronectin expression. Mesangial and proximal tubular epithelial cells exposed to high glucose showed augmented expression of miR-214...
July 12, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28697727/intermedin-attenuates-renal-fibrosis-by-induction-of-heme-oxygenase-1-in-rats-with-unilateral-ureteral-obstruction
#18
Xi Qiao, Lihua Wang, Yanhong Wang, Xiaole Su, Yufeng Qiao, Yun Fan, Zhiqiang Peng
BACKGROUND: Intermedin [IMD, adrenomedullin-2 (ADM-2)] attenuates renal fibrosis by inhibition of oxidative stress. However, the precise mechanisms remain unknown. Heme oxygenase-1 (HO-1), an antioxidant agent, is associated with antifibrogenic effects. ADM is known to induce HO-1. Whether IMD has any effect on HO-1 is unclear. Herein, we determined whether the antifibrotic properties of IMD are mediated by induction of HO-1. METHODS: Renal fibrosis was induced by unilateral ureteral obstruction (UUO) performed on male Wistar rats...
July 11, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28689812/ibmx-protects-human-proximal-tubular-epithelial-cells-from-hypoxic-stress-through-suppressing-hypoxia-inducible-factor-1%C3%AE-expression
#19
Arif Ul Hasan, Wararat Kittikulsuth, Fuminori Yamaguchi, Tuba Musarrat Ansary, Asadur Rahman, Yuki Shibayama, Daisuke Nakano, Hirofumi Hitomi, Masaaki Tokuda, Akira Nishiyama
Hypoxia predisposes renal fibrosis. This study was conducted to identify novel approaches to ameliorate the pathogenic effect of hypoxia. Using human proximal tubular epithelial cells we showed that a pan-phosphodiesterase (PDE) inhibitor, 3-isobutyl-1-methylxanthine (IBMX) dose and time dependently downregulated hypoxia-inducible factor 1α (HIF-1α) mRNA expression, which was further augmented by addition of a transcriptional inhibitor, actinomycin D. IBMX also increased the cellular cyclic adenosine monophosphate (cAMP) level...
July 6, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28680822/paricalcitol-attenuates-lipopolysaccharide-induced-inflammation-and-apoptosis-in-proximal-tubular-cells-through-the-prostaglandin-e2-receptor-ep4
#20
Yu Ah Hong, Keum Jin Yang, So Young Jung, Yoon Kyung Chang, Cheol Whee Park, Chul Woo Yang, Suk Young Kim, Hyeon Seok Hwang
BACKGROUND: Vitamin D is considered to exert a protective effect on various renal diseases but its underlying molecular mechanism remains poorly understood. This study aimed to determine whether paricalcitol attenuates inflammation and apoptosis during lipopolysaccharide (LPS)-induced renal proximal tubular cell injury through the prostaglandin E2 (PGE2) receptor EP4. METHODS: Human renal tubular epithelial (HK-2) cells were pretreated with paricalcitol (2 ng/mL) for 1 hour and exposed to LPS (1 μg/mL)...
June 2017: Kidney Research and Clinical Practice
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