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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/29738843/transporter-dependent-cytotoxicity-of-antiviral-drugs-in-primary-cultures-of-human-proximal-tubular-cells
#2
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
#3
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
#4
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/29683083/indoxyl-sulfate-induces-apoptosis-and-hypertrophy-in-human-kidney-proximal-tubular-cells
#5
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/29669350/periplaneta-americana-extract-may-attenuate-renal-fibrosis-through-inhibiting-janus-tyrosine-kinase-2-signal-transducer-and-activator-of-transcription-3-pathway
#6
Jingsong Liu, Lin Zhou, Liyu He, Ying Zhong, Xiaobai Zhang, Bofei Xiao, Guoyong Liu
BACKGROUND: Periplaneta americana is one of the ancient insect groups with the strongest vitality. Periplaneta americana extract (PAE) has been explored as an alternative remedy for many diseases. Although much progress has been made in the study about PAE, the role of the drug in renal disease is rarely reported, especially in renal fibrosis. This study was designed to evaluate the renoprotective effect of PAE treatment to renal fibrosis. METHOD: An in vivo, unilateral ureteral obstruction (UUO) mouse model was built...
April 17, 2018: Pharmacology
https://www.readbyqxmd.com/read/29593848/saturated-fatty-acids-bound-to-albumin-enhance-osteopontin-expression-and-cleavage-in-renal-proximal-tubular-cells
#7
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/29587265/transforming-growth-factor-beta-1-drives-a-switch-in-connexin-mediated-cell-to-cell-communication-in-tubular-cells-of-the-diabetic-kidney
#8
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/29568897/mir-29b-regulates-ang-ii-induced-emt-of-rat-renal-tubular-epithelial-cells-via-targeting-pi3k-akt-signaling-pathway
#9
Hongtao Hu, Shuang Hu, Shen Xu, Yue Gao, Fang Zeng, Hua Shui
Renal interstitial fibrosis is a necessary step in the progression of chronic kidney to end stage renal disease. MicroRNA-29 (miR-29) has been shown to play essential roles in epithelial-mesenchymal transition (EMT), and thus may contribute to the regulation of renal interstitial fibrosis. However, the role of miR-29 in the regulation of EMT during chronic kidney disease and renal transplantation has been a source of intense debate, and the mechanisms underlying this process are incompletely understood. In this study, we investigated the function of miR-29b in the regulation of EMT and to gain a better understanding of the mechanism by which miR-29b modulates EMT by targeting the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway during the process of renal interstitial fibrosis...
March 22, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29556720/polymyxin-b-causes-dna-damage-in-hk-2-cells-and-mice
#10
B Yun, T Zhang, M A K Azad, J Wang, C J Nowell, P Kalitsis, T Velkov, D F Hudson, J Li
Increasing incidence of multidrug-resistant bacteria presents an imminent risk to global health. Polymyxins are 'last-resort' antibiotics against Gram-negative 'superbugs'; however, nephrotoxicity remains a key impediment in their clinical use. Molecular mechanisms underlying this nephrotoxicity remain poorly defined. Here, we examined the pathways which led to polymyxin B induced cell death in vitro and in vivo. Human proximal tubular cells were treated with polymyxin B (12.5-100 μM) for up to 24 h and showed a significant increase in micronuclei frequency, as well as abnormal mitotic events (over 40% in treated cells, p < 0...
March 20, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29545177/estrogen-related-receptor-%C3%AE-is-essential-for-maintaining-mitochondrial-integrity-in-cisplatin-induced-acute-kidney-injury
#11
Keigo Tsushida, Katsuyuki Tanabe, Kana Masuda, Satoshi Tanimura, Hiromasa Miyake, Yuka Arata, Hitoshi Sugiyama, Jun Wada
Acute kidney injury (AKI) has been associated with not only higher in-hospital mortality but also the subsequent development of chronic kidney disease (CKD). Recent evidence has suggested the involvement of mitochondrial dysfunction and impaired dynamics in the pathogenesis of AKI. Estrogen-related receptor α (ERRα) is an orphan nuclear receptor that acts as a transcription factor to regulate the transcription of genes required for mitochondrial biogenesis and oxidative phosphorylation. In the present study, we examined the effects of ERRα deficiency on the progression of AKI induced by cisplatin...
April 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29476062/histone-deacetylase-inhibitors-protect-against-cisplatin-induced-acute-kidney-injury-by-activating-autophagy-in-proximal-tubular-cells
#12
Jing Liu, Man J Livingston, Guie Dong, Chengyuan Tang, Yunchao Su, Guangyu Wu, Xiao-Ming Yin, Zheng Dong
Histone deacetylase inhibitors (HDACi) have therapeutic effects in models of various renal diseases including acute kidney injury (AKI); however, the underlying mechanism remains unclear. Here we demonstrate that two widely tested HDACi (suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA)) protect the kidneys in cisplatin-induced AKI by enhancing autophagy. In cultured renal proximal tubular cells, SAHA and TSA enhanced autophagy during cisplatin treatment. We further verified the protective effect of TSA against cisplatin-induced apoptosis in these cells...
February 23, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29435202/podocyte-derived-microparticles-promote-proximal-tubule-fibrotic-signaling-via-p38-mapk-and-cd36
#13
Mercedes N Munkonda, Shareef Akbari, Chloe Landry, Suzy Sun, Fengxia Xiao, Maddison Turner, Chet E Holterman, Rania Nasrallah, Richard L Hébert, Christopher R J Kennedy, Dylan Burger
Tubulointerstitial fibrosis is a hallmark of advanced diabetic kidney disease that is linked to a decline in renal function, however the pathogenic mechanisms are poorly understood. Microparticles (MPs) are 100-1000 nm vesicles shed from injured cells that are implicated in intercellular signalling. Our lab recently observed the formation of MPs from podocytes and their release into urine of animal models of type 1 and 2 diabetes and in humans with type 1 diabetes. The purpose of the present study was to examine the role of podocyte MPs in tubular epithelial cell fibrotic responses...
2018: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/29420703/inhibition-of-srebp-with-fatostatin-does-not-attenuate-early-diabetic-nephropathy-in-male-mice
#14
Richard Van Krieken, Mandeep Marway, Pavithra Parthasarathy, Neel Mehta, Alistar J Ingram, Bo Gao, Joan C Krepinsky
Sterol regulatory element binding protein (SREBP) is an important potential mediator of kidney fibrosis, and is known to be upregulated in diabetic nephropathy. Here we evaluate the effectiveness of SREBP inhibition as treatment for diabetic nephropathy.Type 1 diabetes was induced in uninephrectomized male CD1 mice with streptozotocin. Mice were treated with the SREBP inhibitor fatostatin for 12 weeks. At endpoint, kidney function and pathology were assessed. Fatostatin inhibited the increase of both isoforms of SREBP (1 and 2) in diabetic kidneys...
February 5, 2018: Endocrinology
https://www.readbyqxmd.com/read/29402915/amnionless-mediated-glycosylation-is-crucial-for-cell-surface-targeting-of-cubilin-in-renal-and-intestinal-cells
#15
Tomohiro Udagawa, Yutaka Harita, Kenichiro Miura, Jun Mitsui, Koji L Ode, Shinichi Morishita, Seiya Urae, Shoichiro Kanda, Yuko Kajiho, Haruko Tsurumi, Hiroki R Ueda, Shoji Tsuji, Akihiko Saito, Akira Oka
Mutations in either cubilin (CUBN) or amnionless (AMN) genes cause Imerslund-Gräsbeck syndrome (IGS), a hereditary disease characterised by anaemia attributed to selective intestinal malabsorption of cobalamin and low-molecular weight proteinuria. Although cubilin protein does not have a transmembrane segment, it functions as a multi-ligand receptor by binding to the transmembrane protein, amnionless. We established a system to quantitatively analyse membrane targeting of the protein complex in cultured renal and intestinal cells and analysed the pathogenic mechanisms of mutations found in IGS patients...
February 5, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29382757/rgmb-protects-against-acute-kidney-injury-by-inhibiting-tubular-cell-necroptosis-via-an-mlkl-dependent-mechanism
#16
Wenjing Liu, Binbin Chen, Yang Wang, Chenling Meng, Huihui Huang, Xiao-Ru Huang, Jinzhong Qin, Shrikant R Mulay, Hans-Joachim Anders, Andong Qiu, Baoxue Yang, Gordon J Freeman, Hua Jenny Lu, Herbert Y Lin, Zhi-Hua Zheng, Hui-Yao Lan, Yu Huang, Yin Xia
Tubular cell necrosis is a key histological feature of acute kidney injury (AKI). Necroptosis is a type of programed necrosis, which is executed by mixed lineage kinase domain-like protein (MLKL) upon its binding to the plasma membrane. Emerging evidence indicates that necroptosis plays a critical role in the development of AKI. However, it is unclear whether renal tubular cells undergo necroptosis in vivo and how the necroptotic pathway is regulated during AKI. Repulsive guidance molecule (RGM)-b is a member of the RGM family...
February 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29368247/astaxanthin-attenuates-contrast-agent-induced-acute-kidney-injury-in-vitro-and-in-vivo-via-the-regulation-of-sirt1-foxo3a-expression
#17
Nana Liu, Jing Chen, Dongmei Gao, Wenhua Li, Di Zheng
PURPOSE: The study was processed to investigate the effect of astaxanthin (AST; 3,3-dihydroxybeta, beta-carotene-4,4-dione) on the acute kidney injury induced by iohexol and the relationship with SIRT1/FOXO3a signal pathway. METHODS: Thirty male Sprague Dawley rats were randomly divided into five groups as follows: control group (CON; olive oil only), contrast media group, astaxanthin control group (100 mg/kg), low astaxanthin dose group (LAG, 50 mg/kg) and high astaxanthin dose group (HAG, 100 mg/kg)...
January 24, 2018: International Urology and Nephrology
https://www.readbyqxmd.com/read/29357789/current-state-of-in-vitro-cell-based-renal-models
#18
Elnaz Gozalpour, Katherine S Fenner
BACKGROUND: Renal proximal tubule (PT) epithelial cells, expressing uptake and efflux transporters at basolateral and apical membranes, are the location of active renal drug secretion and reabsorption. In addition to singly transfected cells, an in vitro renal cell-based model is a requirement to study the active renal secretion of drugs, drug-drug interactions (DDIs), drug-induced kidney injury, nephrotoxicity holistically, and potentially renal replacement therapies. OBJECTIVES: So far, two-dimensional (2D) cell culture of primary and immortalized PT cells has been the only tool to study drugs active secretion, interactions, and nephrotoxicity, however, a number of in vivo characteristics of cells such as drug transporter expression and function, along with morphological features are lost during in vitro cell culture...
January 18, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29352176/renal-scattered-tubular-like-cells-confer-protective-effects-in-the-stenotic-murine-kidney-mediated-by-release-of-extracellular-vesicles
#19
Xiangyu Zou, Soon Hyo Kwon, Kai Jiang, Christopher M Ferguson, Amrutesh S Puranik, Xiangyang Zhu, Lilach O Lerman
To test the hypothesis that intrinsic renal scattered tubular cells (STC-like cells) contribute to repairing injured tubular epithelial cells (TEC) by releasing extracellular vesicle (EV). EV released from primary cultured pig STC-like cells were confirmed by electron microscopy. Antimycin-A (AMA)-induced injured proximal TEC (PK1 cells) were co-cultured with STC-like cells, STC-like cells-derived EV, or EV-free conditioned-medium for 3 days. Cellular injury, oxidative stress and mitochondrial function were assessed...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330945/cyclosporine-a-induces-endothelin-converting-enzyme-1-studies-in-vivo-and-in-vitro
#20
S N Heyman, Z Abassi, C Rosenberger, H Yaseen, G Skarjinski, A Shina, S Mathia, N Krits, M Khamaisi
AIM: Cyclosporine A (CsA) induces renal vasoconstriction and hypoxia and enhances the expression of endothelin-1 (ET-1) pro-hormone (pre-pro-ET-1), plausibly leading to a feed-forward loop of renal vasoconstriction, hypoxia and enhanced synthesis of the potent vasoconstrictor ET-1. Endothelin-converting enzyme (ECE)-1 cleaves big endothelin to generate endothelin (ET)-1 and is upregulated by hypoxia via hypoxia-inducible factor (HIF). We hypothesized that in addition to the direct induction of ET-1 synthesis, CsA might also intensify renal ECE-1 expression, thus contributing to enhanced ET-1 synthesis following CsA...
May 2018: Acta Physiologica
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