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proximal epithelial tubular

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https://www.readbyqxmd.com/read/29775417/targeting-histone-methyltransferase-enhancer-of-zeste-homolog-2-inhibits-renal-epithelial-mesenchymal-transition-and-attenuates-renal-fibrosis
#1
Xiaoxu Zhou, Chongxiang Xiong, Evelyn Tolbert, Ting C Zhao, George Bayliss, Shougang Zhuang
Enhancer of zeste homolog-2 (EZH2) is a methyltransferase that induces histone H3 lysine 27 trimethylation (H3K27me3) and functions as an oncogenic factor in many cancer types. Its role in renal epithelial-mesenchymal transition (EMT) remains unknown. In this study, we found that EZH2 and H3K27me3 were highly expressed in mouse kidney with unilateral ureteral obstruction and cultured mouse kidney proximal tubular (TKPT) cells undergoing EMT. Inhibition of EZH2 with 3-deazaneplanocin A (3-DZNeP) attenuated renal fibrosis, which was associated with preserving E-cadherin expression and inhibiting Vimentin up-regulation in the obstructed kidney...
May 18, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29773167/optimal-dosage-and-early-intervention-of-l-ascorbic-acid-inhibiting-k-2-cr-2-o-7-induced-renal-tubular-cell-damage
#2
Tzeng-Jih Lin, Yeou-Lih Huang, Jung-San Chang, Kuan-Ting Liu, Meng-Chi Yen, Fen-Wei Chen, Yueh-Lun Shih, Jo-Chi Jao, Po-Chi Huang, I-Jeng Yeh
Chromium poisoning can cause renal failure and death. Chromium intoxication may be managed using L-ascorbic acid (vitamin C) therapy. However, the evidence supporting the effectiveness of this treatment is insufficient, and the mechanism of action has not been clarified in renal cells. In this study, our results showed that the optimal regimen of L-ascorbic acid therapy in human epithelial renal proximal tubule cells, HK-2 cells, was 30 μg/mL. Supplementation of L-ascorbic acid with 30 μg/mL and within 8 h of chromium intoxication (K2 Cr2 O7, Cr6+ ) was effective to inhibit renal tubular cell damage by blocking generation of free radicals, cell apoptosis, and autophagy...
July 2018: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/29772789/downregulation-of-the-s1p-transporter-spinster-homology-protein-2-spns2-exerts-an-anti-fibrotic-and-anti-inflammatory-effect-in-human-renal-proximal-tubular-epithelial-cells
#3
Olivier Blanchard, Bisera Stepanovska, Manuel Starck, Martin Erhardt, Isolde Römer, Dagmar Meyer Zu Heringdorf, Josef Pfeilschifter, Uwe Zangemeister-Wittke, Andrea Huwiler
Sphingosine kinase (SK) catalyses the formation of sphingosine 1-phosphate (S1P), which acts as a key regulator of inflammatory and fibrotic reactions, mainly via S1P receptor activation. Here, we show that in the human renal proximal tubular epithelial cell line HK2, the profibrotic mediator transforming growth factor β (TGFβ) induces SK-1 mRNA and protein expression, and in parallel, it also upregulates the expression of the fibrotic markers connective tissue growth factor (CTGF) and fibronectin. Stable downregulation of SK-1 by RNAi resulted in the increased expression of CTGF, suggesting a suppressive effect of SK-1-derived intracellular S1P in the fibrotic process, which is lost when SK-1 is downregulated...
May 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29769319/repeated-exposure-of-epithelial-cells-to-apoptotic-cells-induces-the-specific-selection-of-an-adaptive-phenotype-implications-for-tumorigenesis
#4
Lanfei Feng, Snezana Vujicic, Michael E Dietrich, Natalia Litbarg, Suman Setty, Angelika Antoni, Joyce Rauch, Jerrold S Levine
The consequences of apoptosis extend beyond mere death of the cell. We have shown that receptor-mediated recognition of apoptotic target cells by viable kidney proximal tubular epithelial cells (PTECs) inhibits PTEC proliferation, growth, and survival. Here we tested the hypothesis that continual exposure to apoptotic targets can induce a phenotypic change in responding PTECs, as in other instances of natural selection. In particular, we demonstrate that repeated exposure to apoptotic targets leads to emergence of a PTEC line (denoted BU...
May 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29738843/transporter-dependent-cytotoxicity-of-antiviral-drugs-in-primary-cultures-of-human-proximal-tubular-cells
#5
Lawrence H Lash, Caroline A Lee, Clynn Wilker, Vishal Shah
The role of plasma membrane transporters in the nephrotoxicity of two antiretroviral drugs, cidofovir and tenofovir, was studied in primary cultures of human proximal tubular (hPT) cells. Cells were grown on Transwell filter inserts to maintain epithelial polarity and access to either the apical or basolateral plasma membrane. The function of relevant membrane transporters, organic anion transporter 1 and 3 (OAT1/3), P-glycoprotein (multidrug resistance protein-1; P-gp or MDR1), and organic cation transporter 2 (OCT2), was validated by measurements of apical-to-basolateral and basolateral-to-apical fluxes of furosemide, digoxin, and metformin, respectively...
May 5, 2018: Toxicology
https://www.readbyqxmd.com/read/29717935/expression-of-soluble-epoxide-hydrolase-in-renal-tubular-epithelial-cells-regulates-macrophage-infiltration-and-polarization-in-iga-nephropathy
#6
Qian Wang, Yan Liang, Yingjin Qiao, Xiangya Zhao, Yi Yang, Shengnan Yang, Bing Li, Qianru Zhao, Ling Dong, Songxia Quan, Rui Tian, Zhangsuo Liu
Tubulointerstitial inflammatory cell infiltration and activation contribute to kidney inflammation and fibrosis. Epoxyeicosatrienoic acids (EETs), which are rapidly metabolized to dihydroxyeicosatrienoic acids by the soluble epoxide hydrolase (sEH), have multiple biological functions, including vasodilation, anti-inflammatory action, and others. Inhibition of sEH has been demonstrated to attenuate inflammation in many renal disease models. However, the relationship between sEH expression and macrophage polarization in kidney remains unknown...
May 2, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29700792/preventive-effect-of-shenkang-injection-against-high-glucose-induced-senescence-of-renal-tubular-cells
#7
Biqiong Fu, Jie Yang, Jia Chen, Lirong Lin, Kehong Chen, Weiwei Zhang, Jianguo Zhang, Yani He
Shenkang injection (SKI) is a classic prescription composed of Radix Astragali, rhubarb, Astragalus, Safflower, and Salvia. This treatment was approved by the State Food and Drug Administration of China in 1999 for treatment of chronic kidney diseases based on good efficacy and safety. This study aimed to investigate the protective effect of SKI against high glucose (HG)-induced renal tubular cell senescence and its underlying mechanism. Primary renal proximal tubule epithelial cells were cultured in (1) control medium (control group), medium containing 5 mmol/L glucose; (2) mannitol medium (mannitol group), medium containing 5 mmol/L glucose, and 25 mmol/L mannitol; (3) HG medium (HG group) containing 30 mmol/L glucose; (4) SKI treatment at high (200 mg/L), medium (100 mg/L), or low (50 mg/L) concentration in HG medium (HG + SKI group); or (5) 200 mg/L SKI treatment in control medium (control + SKI group) for 72 h...
April 25, 2018: Frontiers of Medicine
https://www.readbyqxmd.com/read/29693725/tctex-1-a-novel-interaction-partner-of-kidney-injury-molecule-1-is-required-for-efferocytosis
#8
Ola Z Ismail, Saranga Sriranganathan, Xizhong Zhang, Joseph V Bonventre, Antonis S Zervos, Lakshman Gunaratnam
Kidney injury molecule-1 (KIM-1) is a phosphatidylserine receptor that is specifically upregulated on proximal tubular epithelial cells (PTECs) during acute kidney injury and mitigates tissue damage by mediating efferocytosis (the phagocytic clearance of apoptotic cells). The signaling molecules that regulate efferocytosis in TECs are not well understood. Using a yeast two-hybrid screen, we identified the dynein light chain protein, Tctex-1, as a novel KIM-1-interacting protein. Immunoprecipitation and confocal imaging studies suggested that Tctex-1 associates with KIM-1 in cells at baseline, but, dissociates from KIM-1 within 90 min of initiation of efferocytosis...
April 25, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29693270/uremic-encephalopathy-in-a-rhesus-macaque-macaca-mulatta-a-case-report-and-a-brief-review-of-the-veterinary-literature
#9
REVIEW
Allison Mustonen, Olga Gonzalez, Elda Mendoza, Shyamesh Kumar, Edward J Dick
BACKGROUND: Uremic encephalopathy is uncommon yet is one of the most severe complications of renal failure. We present a case of acute renal failure and associated cerebral and vascular lesions consistent with uremic encephalopathy in a rhesus macaque (Macaca mulatta). METHODS: A 14-year-old, female, specific-pathogen-free rhesus macaque presented in lateral recumbency, obtunded, severely dehydrated, and hypothermic, with severe azotemia, mild hyponatremia, hypokalemia, hypochloremia, increased anion gap, and hypercholesterolemia...
April 25, 2018: Journal of Medical Primatology
https://www.readbyqxmd.com/read/29683083/indoxyl-sulfate-induces-apoptosis-and-hypertrophy-in-human-kidney-proximal-tubular-cells
#10
Robert J Ellis, David M Small, Keng Lim Ng, David A Vesey, Luis Vitetta, Ross S Francis, Glenda C Gobe, Christudas Morais
Indoxyl sulfate (IS) is a protein-bound uremic toxin that accumulates in patients with declining kidney function. Although generally thought of as a consequence of declining kidney function, emerging evidence demonstrates direct cytotoxic role of IS on endothelial cells and cardiomyocytes, largely through the expression of pro-inflammatory and pro-fibrotic factors. The direct toxicity of IS on human kidney proximal tubular epithelial cells (PTECs) remains a matter of debate. The current study explored the effect of IS on primary cultures of human PTECs and HK-2, an immortalized human PTEC line...
January 1, 2018: Toxicologic Pathology
https://www.readbyqxmd.com/read/29653103/sterol-regulatory-element-binding-protein-1-trans-activates-25-hydroxy-vitamin-d-3-24-hydroxylase-gene-expression-in-renal-proximal-tubular-cells
#11
Tomohiro Kagawa, Mina Kozai, Masashi Masuda, Nagakatsu Harada, Otoki Nakahashi, Mari Tajiri, Ryouhei Yoshikawa, Mari Nakao, Yuichiro Takei, Masayuki Iwano, Eiji Takeda, Yutaka Taketani, Hironori Yamamoto
The physiological activity of the steroid derived hormone vitamin D is regulated by several enzymatic steps. Both 25-hydroxy vitamin D3 1α-hydroxylase (CYP27B1) and 25-hydroxyvitamin D3 24-hydroxylase (CYP24A1) modulate blood levels of 1,25-dihydroxyvitamin D3 , an activated form of vitamin D. We previously demonstrated that CYP27B1 expression was trans-activated by sterol regulatory element binding protein 1 (SREBP1), although whether SREBP1 also regulates CYP24A1 transcription was unclear. Here we investigated the ability of SREBP1 to affect CYP24A1 transcription...
April 10, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29651904/adaptor-protein-1-b-mu-subunit-does-not-contribute-to-the-recycling-of-kae1-protein-in-polarized-renal-epithelial-cells
#12
Ensaf Y Almomani, Nicolas Touret, Emmanuelle Cordat
Mutations in the gene encoding the kidney anion exchanger 1 (kAE1) can lead to distal renal tubular acidosis (dRTA). dRTA mutations reported within the carboxyl (C)-terminal tail of kAE1 result in apical mis-targeting of the exchanger in polarized renal epithelial cells. As kAE1 physically interacts with the μ subunit of epithelial adaptor protein 1 B (AP-1B), we investigated the role of heterologously expressed μ1B subunit of the AP-1B complex for kAE1 retention to the basolateral membrane in polarized porcine LLC-PK1 renal epithelial cells that are devoid of endogenous AP-1B...
April 13, 2018: Molecular Membrane Biology
https://www.readbyqxmd.com/read/29620262/dynamic-expression-and-roles-of-sequestome%C3%A2-1-p62-in-lps%C3%A2-induced-acute-kidney-injury-in-mice
#13
Ting Li, Jie Zhao, Shuying Miao, Yunfei Xu, Xianzhong Xiao, Ying Liu
Acute kidney injury (AKI) is one of the most common complications of sepsis. The roles of autophagy in AKI have been demonstrated in previous studies. Sequestosome‑1 (p62) has been demonstrated to serve essential roles in autophagy. The dysregulation of autophagy causes p62 accumulation, which is associated with increased inflammation and tumorigenesis. However, the expression patterns and role of p62 in septic AKI remain unknown. The present study detected the renal autophagy level, and the expression and localization of p62, in a lipopolysaccharide (LPS)‑induced AKI mouse model...
March 28, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29619879/cisplatin-induced-oxidative-stress-stimulates-renal-fas-ligand-shedding
#14
Hitesh Soni, Damian Kaminski, Rajashekhar Gangaraju, Adebowale Adebiyi
Acute kidney injury (AKI), a significant complication of cisplatin chemotherapy is associated with reactive oxygen species (ROS)-dependent renal cell death, but the cellular targets of ROS in cisplatin nephrotoxicity are not fully resolved. Here, we investigated cisplatin-induced oxidative renal damage and tested the hypothesis that ROS-dependent shedding of death activator Fas ligand (FasL) occurs in cisplatin nephropathy. We show that intraperitoneal injection of sulfobutyl ether-β-cyclodextrin (Captisol™)-solubilized cisplatin elevated the level of lipid peroxidation product malondialdehyde in mouse kidneys and urinary concentration of oxidative DNA damage biomarker 8-hydroxy-2'-deoxyguanosine...
November 2018: Renal Failure
https://www.readbyqxmd.com/read/29606257/-ifosphamide-nephrotoxicity
#15
Gaël Ensergueix, Alexandre Karras
Ifosfamide is a cytotoxic drug usually used in malignant sarcomas. The nephrotoxicity of this agent has been described essentially among children, revealed by renal failure and proximal tubulopathy. We recently conducted a retrospective multicentre study, describing 34 adult patients admitted for ifosfamide nephrotoxicity. More than 80% of them presented with renal failure, diagnosed up to 48 months after ifosfamide administration. A Fanconi syndrome with hypophosphoremia, hypokaliemia, glucosuria and low-molecular weight proteinuria, was present in two third of all cases...
April 2018: Néphrologie & Thérapeutique
https://www.readbyqxmd.com/read/29603641/donor-kidney-injury-molecule-1-promotes-graft-recovery-by-regulating-systemic-necroinflammation
#16
Ji Yun Lee, Ola Z Ismail, Xizhong Zhang, Aaron Haig, Dameng Lian, Lakshman Gunaratnam
Ischemia-reperfusion injury during kidney transplantation predisposes to delayed graft function, rejection, and premature graft failure. Exacerbation of tissue damage and alloimmune responses may be explained by necroinflammation: an autoamplification loop of cell death and inflammation, which is mediated by the release of damage-associated molecular patterns (e.g. HMGB1) from necrotic cells that activate both innate and adaptive immune pathways. Kidney Injury Molecule-1 (KIM-1) is a phosphatidylserine receptor that is upregulated on injured proximal tubular epithelial cells and enables them to clear apoptotic and necrotic cells...
March 30, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29593848/saturated-fatty-acids-bound-to-albumin-enhance-osteopontin-expression-and-cleavage-in-renal-proximal-tubular-cells
#17
Alyssa Cobbs, Kristopher Ballou, Xiaoming Chen, Jasmine George, Xueying Zhao
Osteopontin (OPN) is one of the proinflammatory cytokines upregulated in the kidneys of diabetic animals and patients with nephropathy. An increase in urinary albumin and albumin-bound fatty acids (FA) presents a proinflammatory environment to the proximal tubules in proteinuric kidney diseases including diabetic nephropathy. This study was designed to examine if FA overload could stimulate OPN expression and cleavage in renal tubule epithelial cells. OPN gene and protein expression was examined in the kidney of Zucker diabetic (ZD) rats and cultured proximal tubular cells exposed to either bovine serum albumin (BSA) or BSA conjugated with palmitic acid (PA), the most abundant saturated plasma FA...
2018: International Journal of Physiology, Pathophysiology and Pharmacology
https://www.readbyqxmd.com/read/29590662/urinary-iron-excretion-is-associated-with-urinary-full-length-megalin-and-renal-oxidative-stress-in-chronic-kidney-disease
#18
Shinya Nakatani, Ayumi Nakatani, Eiji Ishimura, Norikazu Toi, Akihiro Tsuda, Katsuhito Mori, Masanori Emoto, Yoshiaki Hirayama, Akihiko Saito, Masaaki Inaba
BACKGROUND/AIMS: Megalin mediates the uptake of glomerular-filtered iron in the proximal tubules. Urinary full length megalin (C-megalin) excretion has been found to be increased in association with megalin-mediated metabolic load to the endo-lysosomal system in proximal tubular epithelial cells (PTECs) of residual nephrons. In the present study, we investigated the association between urinary iron and C-megalin in chronic kidney disease (CKD) patients, and the possible harmful effect of iron in renal tubules...
March 22, 2018: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29587265/transforming-growth-factor-beta-1-drives-a-switch-in-connexin-mediated-cell-to-cell-communication-in-tubular-cells-of-the-diabetic-kidney
#19
Claire Hills, Gareth William Price, Mark John Wall, Timothy John Kaufmann, Sidney Chi-Wai Tang, Wai Han Yiu, Paul Edward Squires
BACKGROUND/AIMS: Changes in cell-to-cell communication have been linked to several secondary complications of diabetes, but the mechanism by which connexins affect disease progression in the kidney is poorly understood. This study examines a role for glucose-evoked changes in the beta1 isoform of transforming growth factor (TGFβ1), on connexin expression, gap-junction mediated intercellular communication (GJIC) and hemi-channel ATP release from tubular epithelial cells of the proximal renal nephron...
March 26, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29581579/restoration-of-e-cadherin-by-ppbica-protects-against-cisplatin-induced-acute-kidney-injury-by-attenuating-inflammation-and-programmed-cell-death
#20
Li Gao, Ming-Ming Liu, Hong-Mei Zang, Qiu-Ying Ma, Qin Yang, Ling Jiang, Gui-Ling Ren, Hai-Di Li, Wei-Feng Wu, Jia-Nan Wang, Biao Wei, Xue-Qi Liu, Cheng Jiang, Cheng Huang, Jun Li, Xiao-Ming Meng
E-cadherin is a major component of tubular adherent proteins that maintain intercellular contacts and cell polarity in epithelial tissue. It is involved in pathological processes of renal cell carcinoma and fibrotic diseases via epithelial-mesenchymal transition. Although studies have shown E-cadherin is significantly downregulated in acute kidney injury (AKI), its function in AKI is unknown. Here, we evaluated cell damage and inflammation in cisplatin-stimulated tubular epithelial cell lines after disrupting E-cadherin and restoring it with PPBICA, a small molecule identified by high-throughput screening...
March 26, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
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