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https://www.readbyqxmd.com/read/28715434/engineered-extracellular-matrices-with-controlled-mechanics-modulate-renal-proximal-tubular-cell-epithelialization
#1
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
#2
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 11, 2017: Toxicology
https://www.readbyqxmd.com/read/28709637/tubulointerstitial-fibrosis-can-sensitize-the-kidney-to-subsequent-glomerular-injury
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/28677767/lysyl-oxidase%C3%A2-like-2-is-expressed-in-kidney-tissue-and-is-associated-with-the-progression-of-tubulointerstitial-fibrosis
#11
Sung-Eun Choi, Nara Jeon, Hoon Young Choi, Jae Il Shin, Hyeon Joo Jeong, Beom Jin Lim
Tubulointerstitial fibrosis is a common end point of chronic kidney diseases, and preventing its progression is key to avoiding renal failure. Transforming growth factor‑β (TGF‑β) and associated molecules promote tubulointerstitial fibrosis; however, effective therapies targeting these molecules have yet to be developed. Lysyl oxidase‑like 2 (LOXL2), which is involved in invasive growth and metastasis of malignant neoplasms, has recently been reported to serve a key role in hepatic and pulmonary fibrosis...
July 4, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28672921/the-mechanism-of-blood-concentrations-of-the-shenqi-pill-repairing-injured-epithelial-cells-of-renal-tubular-in-vitro
#12
Fei Huang, Wenfeng Ma
In the present study, we investigated the best blood concentration of the mechanism of Shenqi pill repairing the injured epithelial cells of renal tubular in vitro. First, the injured hypoxia/reoxygenation model of rat proximal renal tubular epithelial cell strain (NRK-52E) was established. The animals were divided randomly into control, model, low concentration (5 µg/ml), moderate concentration (10 µg/ml) and high concentration (20 µg/ml) groups. The apoptotic rate was measured with flow cytometry and Jag2/Notch2/hes1 mRNA, and the protein expression was measured for 1, 3 and 7 days...
July 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28650379/tenofovir-induced-toxicity-in-renal-proximal-tubular-epithelial-cells-involvement-of-mitochondria
#13
Lara Milián, José E Peris, Patricia Gandía, Isabel Andújar, Luis Pallardó, Jose L Górriz, Ana Blas-García
OBJECTIVE: In-vivo studies suggest that mitochondria is involved in tenofovir (TFV)-induced renal toxicity, but the underlying mechanisms are still unclear. The aim of the present study was to assess the effects of TFV and its prodrug, TFV disoproxil fumarate, on mitochondrial function and cell survival/viability in a renal proximal tubular cell line. DESIGN AND METHODS: We evaluated parameters of cellular proliferation/survival (cell count, cell cycle, viability) and mitochondrial function (oxygen consumption, mitochondrial membrane potential, reactive oxygen species production) in NRK-52E cells...
July 31, 2017: AIDS
https://www.readbyqxmd.com/read/28627391/low-molecular-weight-fucoidan-and-its-fractions-inhibit-renal-epithelial-mesenchymal-transition-induced-by-tgf-%C3%AE-1-or-fgf-2
#14
Xinpeng Li, Xiaohong Li, Quanbin Zhang, Tingting Zhao
We investigated the renal protective effects of low molecular weight fucoidan (LMWF) and its two fractions (F0.5 and F1.0), which were extracted from Laminaria japonica, on the epithelial-mesenchymal transition (EMT) induced by transforming growth factor beta 1 (TGF-β1) and fibroblast growth factor 2 (FGF-2) in HK-2 human renal proximal tubular cells. Cell morphology and EMT markers (fibronectin and alpha-smooth muscle actin) demonstrated that cells treated with TGF-β1 or FGF-2 developed EMT to a significant extent...
June 13, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28625483/silymarin-protects-against-renal-injury-through-normalization-of-lipid-metabolism-and-mitochondrial-biogenesis-in-high-fat-fed-mice
#15
Bin Feng, Ran Meng, Bin Huang, Yan Bi, Shanmei Shen, Dalong Zhu
Obesity is associated with an increased risk of chronic kidney diseases and the conventional treatment with renin-angiotensin-aldosterone system (RAAS) inhibitors is not enough to prevent renal injury and prolong the progression of disease. Recently, silymarin has shown protective effects on renal tissue injury, but the underlying mechanisms remain elusive. The goal of this study was to investigate the potential capacity of silymarin to prevent renal injury during obesity induced by high fat diet (HFD) in mice...
June 15, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28614065/microrna-423-5p-facilitates-hypoxia-reoxygenation-induced-apoptosis-in-renal-proximal-tubular-epithelial-cells-by-targeting-gstm1-via-endoplasmic-reticulum-stress
#16
Xiao-Peng Yuan, Long-Shan Liu, Chuan-Bao Chen, Jian Zhou, Yi-Tao Zheng, Xiao-Ping Wang, Ming Han, Chang-Xi Wang
It has been reported that microRNAs (miRs) can regulate renal response to acute injury and members of them are believed to be important in maintenance of renal function and development of renal injury. We investigated the actions of microRNA-423-5p (miR-423-5p) and glutathione-S-transferase (GST) M1 after acute kidney injury. MiR-423-5p was up-regulated and GSTM1 was down-regulated in human kidney (HK-2) cells subjected to hypoxia/reoxygenation (H/R) and in rat kidneys subjected to ischemia/reperfusion (I/R) injury...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28606862/pathogenicity-profile-of-vibrio-parahaemolyticus-in-farmed-pacific-white-shrimp-penaeus-vannamei
#17
R Ananda Raja, R Sridhar, C Balachandran, A Palanisammi, S Ramesh, K Nagarajan
A pathobiological study was conducted using Vibrio parahaemolyticus (VP) strain isolated from vibriosis affected shrimp (Penaeus vannamei) farms in Kancheepuram and Thiruvallur districts of Tamil Nadu during August 2014 to February 2015. The isolate was identified based on the morphological, physiological, biochemical and molecular characters. LD50 value with intramuscular injection was determined as 2.6 × 10(4) cfu/shrimp and sequential pathology was studied giving 6.1 × 10(3) cfu/shrimp (LD25). Total plate count (TPC) and total Vibrio count (TVC) in water, pond sediment, haemolymph, muscle, HP and gut were found significantly (P < 0...
August 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28606242/-effects-of-microrna-145-on-epithelial-mesenchymal-transition-of-tgf-%C3%AE-1-induced-human-renal-proximal-tubular-epithelial-cells
#18
Hua Liu, Xiao-Jie He, Guo-Jun Li, Qing-Xiong Ding, Wan-Xia Liang, Juan Fan
OBJECTIVE: To investigate the effects of microRNA-145 (miR-145) on epithelial-mesenchymal transition (EMT) of TGF-β1-induced human renal proximal tubular epithelial (HK-2) cells. METHODS: The gene sequence of miR-145 was synthesized and cloned into pCMV-myc to construct recombinant plasmid pCMV-miR-145. HK-2 cells were divided into four groups: control (untreated), TGF-β1 (treated with TGF-β1), blank+TGF-β1 (treated with TGF-β1 after HK-2 cells transfected with blank plasmid) and miR-145+TGF-β1 (treated with TGF-β1 after HK-2 cells transfected with pCMV-miR-145 recombinant plasmid)...
June 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28600680/tight-junctions-of-the-proximal-tubule-and-their-channel-proteins
#19
REVIEW
Michael Fromm, Jörg Piontek, Rita Rosenthal, Dorothee Günzel, Susanne M Krug
The renal proximal tubule achieves the majority of renal water and solute reabsorption with the help of paracellular channels which lead through the tight junction. The proteins forming such channels in the proximal tubule are claudin-2, claudin-10a, and possibly claudin-17. Claudin-2 forms paracellular channels selective for small cations like Na(+) and K(+). Independently of each other, claudin-10a and claudin-17 form anion-selective channels. The claudins form the paracellular "pore pathway" and are integrated, together with purely sealing claudins and other tight junction proteins, in the belt of tight junction strands surrounding the tubular epithelial cells...
June 9, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28594240/dimethylarginine-dimethylaminohydrolase-1-deficiency-induces-the-epithelial-to-mesenchymal-transition-in-renal-proximal-tubular-epithelial-cells-and-exacerbates-kidney-damage-in-aged-and-diabetic-mice
#20
Linlin Shi, Chenyang Zhao, Hongyun Wang, Tong Lei, Shasha Liu, Jianwei Cao, Zhongbing Lu
AIMS: Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is mainly degraded by dimethylarginine dimethylaminohydrolase (DDAH). Emerging evidence suggests that plasma ADMA accumulation and DDAH1 activity/expression reduction are linked to chronic kidney disease (CKD) pathology, but the mechanisms remain largely unknown. Here, we examined the role of ADMA/DDAH1 in the epithelial-mesenchymal transition (EMT) of tubular epithelial cells (TECs), an important mechanism for the pathogenesis of renal fibrosis...
July 7, 2017: Antioxidants & Redox Signaling
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