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autophagy acute kidney injury

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https://www.readbyqxmd.com/read/29739813/interleukin-1-%C3%AE-activates-a-myc-dependent-metabolic-switch-in-kidney-stromal-cells-necessary-for-progressive-tubulointerstitial-fibrosis
#1
Dario R Lemos, Michael McMurdo, Gamze Karaca, Julia Wilflingseder, Irina A Leaf, Navin Gupta, Tomoya Miyoshi, Koichiro Susa, Bryce G Johnson, Kirolous Soliman, Guanghai Wang, Ryuji Morizane, Joseph V Bonventre, Jeremy S Duffield
Background Kidney injury is characterized by persisting inflammation and fibrosis, yet mechanisms by which inflammatory signals drive fibrogenesis remain poorly defined. Methods RNA sequencing of fibrotic kidneys from patients with CKD identified a metabolic gene signature comprising loss of mitochondrial and oxidative phosphorylation gene expression with a concomitant increase in regulators and enzymes of glycolysis under the control of PGC1 α and MYC transcription factors, respectively. We modeled this metabolic switch in vivo , in experimental murine models of kidney injury, and in vitro in human kidney stromal cells (SCs) and human kidney organoids...
May 8, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29732938/the-protective-role-of-autophagy-in-nephrotoxicity-induced-by-bismuth-nanoparticles-through-ampk-mtor-pathway
#2
Yongming Liu, Huan Yu, Xihui Zhang, Yong Wang, Zhentao Song, Jian Zhao, Haibin Shi, Ruibin Li, Yangyun Wang, Leshuai W Zhang
Bismuth is widely used in metallurgy, cosmetic industry, and medical diagnosis and recently, bismuth nanoparticles (NPs) (BiNP) have been made and proved to be excellent CT imaging agents. Previously, we have synthesized bovine serum albumin based BiNP for imaging purpose but we found a temporary kidney injury by BiNP. Due to the reported adverse events of bismuth on human health, we extended our studies on the mechanisms for BiNP induced nephrotoxicity. Blood biochemical analysis indicated the increase in creatinine (CREA) and blood urea nitrogen (BUN), and intraluminal cast formation with cell apoptosis/necrosis was evident in proximal convoluted tubules (PCTs) of mice...
May 6, 2018: Nanotoxicology
https://www.readbyqxmd.com/read/29704511/ngal-attenuates-renal-ischemia-reperfusion-injury-through-autophagy-activation-and-apoptosis-inhibition-in-rats
#3
Ya-Li Zhang, Shu-Kai Qiao, Rong-Ying Wang, Xiao-Nan Guo
Ischemia/reperfusion (I/R) injury is a main cause of acute kidney injury (AKI), and currently lacks effective therapies. This study is to investigate the level of Neutrophil gelatinase-associated lipocalin (NGAL) and autophagy status during renal I/R injury, so as to determine whether the exogenous NGAL protein could exert a protective effect for I/R injury and explore the potential mechanisms. Forty male Wistar rats were randomly divided into the following four groups: Sham, I/R, pre-treated with NGAL before I/R (I/R + pre-N), treated with NGAL after I/R (I/R + post-N)...
April 25, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29701108/acute-kidney-injury-as-a-condition-of-renal-senescence
#4
Lucia Andrade, Camila E Rodrigues, Samirah A Gomes, Irene L Noronha
Acute kidney injury (AKI), characterized by a sharp drop in glomerular filtration, continues to be a significant health burden because it is associated with high initial mortality, morbidity, and substantial health-care costs. There is a strong connection between AKI and mechanisms of senescence activation. After ischemic or nephrotoxic insults, a wide range of pathophysiological events occur. Renal tubular cell injury is characterized by cell membrane damage, cytoskeleton disruption, and DNA degradation, leading to tubular cell death by necrosis and apoptosis...
January 1, 2018: Cell Transplantation
https://www.readbyqxmd.com/read/29680838/mitophagy-plays-a-protective-role-in-iodinated-contrast-induced-acute-renal-tubular-epithelial-cells-injury
#5
Rong Lei, Fei Zhao, Cheng-Yuan Tang, Min Luo, Shi-Kun Yang, Wei Cheng, Xu-Wei Li, Shao-Bin Duan
BACKGROUND/AIMS: Contrast induced-acute kidney injury (CI-AKI) is one of the most common causes of acute kidney injury (AKI) in hospitalized patients. Mitophagy, the selective elimination of mitochondria via autophagy, is an important mechanism of mitochondrial quality control in physiological and pathological conditions. In this study, we aimed to determine effects of iohexol and iodixanol on mitochondrial reactive oxygen species (ROS), mitophagy and the potential role of mitophagy in CI-AKI cell models...
2018: Cellular Physiology and Biochemistry
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
#6
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/29607326/ischemic-preconditioning-promotes-autophagy-and-alleviates-renal-ischemia-reperfusion-injury
#7
Ying Xie, Jing Xiao, Chensheng Fu, Zhenxing Zhang, Zhibin Ye, Xiaoli Zhang
Autophagy is important for cellular survival during renal ischemia/reperfusion (I/R) injury. Ischemic preconditioning (IPC) has a strong renoprotective effect during renal I/R. Our study here aimed to explore the effect of IPC on autophagy during renal I/R injury. Rats were subjected to unilateral renal ischemia with or without prior IPC. Hypoxia/reoxygenation (H/R) injury was induced in HK-2 cells with or without prior hypoxic preconditioning (HPC). Autophagy and apoptosis were detected after reperfusion or reoxygenation for different time...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29575816/kidney-derived-c-kit-cells-possess-regenerative-potential
#8
Samirah A Gomes, Joshua M Hare, Erika B Rangel
Kidney-derived c-Kit+ cells exhibit progenitor/stem cell properties in vitro (self-renewal capacity, clonogenicity, and multipotentiality). These cells can regenerate epithelial tubular cells following ischemia-reperfusion injury and accelerate foot processes effacement reversal in a model of acute proteinuria in rats. Several mechanisms are involved in kidney regeneration by kidney-derived c-Kit+ cells, including cell engraftment and differentiation into renal-like structures, such as tubules, vessels, and podocytes...
April 2018: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29504713/tak1-mediates-excessive-autophagy-via-p38-and-erk-in-cisplatin-induced-acute-kidney-injury
#9
Jun Zhou, Youling Fan, Jiying Zhong, Zhenxing Huang, Teng Huang, Sen Lin, Hongtao Chen
The ability of cisplatin (cis-diamminedichloroplatinum II) toxicity to induce acute kidney injury (AKI) has attracted people's attention and concern for a long time, but its molecular mechanisms are still widely unknown. We found that the expression of transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) could be increased in kidneys of mice administrated with cisplatin. Autophagy is an evolutionarily conserved catabolic pathway and is involved in various acute and chronic injuries. Moreover, p38 MAPK (mitogen-activated protein kinase) and ERK regulate autophagy in response to various stimuli...
May 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29500224/tlr2-and-tlr4-play-opposite-role-in-autophagy-associated-with-cisplatin-induced-acute-kidney-injury
#10
Magaiver Andrade-Silva, Marcos Antônio Cenedeze, Luiz Augusto Perandini, Raphael José Ferreira Felizardo, Ingrid Mizuno Watanabe, Juan Sebastian Henao Agudelo, Ângela Castoldi, Giselle Martins Gonçalves, Clarice Silvia Taemi Origassa, Patricia Semedo, Meire Ioshie Hiyane, Orestes Foresto Neto, Denise Maria Avancini Costa Malheiros, Marlene Antonia Reis, Clarice Kazue Fujihara, Roberto Zatz, Alvaro Pacheco-Silva, Niels Olsen Saraiva Câmara, Danilo Candido de Almeida
Acute kidney injury (AKI) is considered an inflammatory disease in which Toll-like receptors (TLRs) signaling pathways play an important role. The activation of TLRs results in production of several inflammatory cytokines leading to further renal damage. In contrast, TLRs are key players on autophagy induction, which is associated with a protective function on cisplatin-induced AKI. Hence, this study aimed evaluate the specific participation of TLR2 and TLR4 molecules on development of cisplatin-induced AKI...
March 2, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29497318/klotho-ameliorates-sepsis-induced-acute-kidney-injury-but-is-irrelevant-to-autophagy
#11
Xinxin Chen, Huan Tong, Yu Chen, Chaosheng Chen, Jingjing Ye, Qingfei Mo, Guangju Zhao, Guangliang Hong, Chenfei Zheng, Zhongqiu Lu
Background: The role of Klotho (KL) in sepsis-induced acute kidney injury (AKI) and the potential relationship between KL and autophagy in septic AKI were investigated. Materials and methods: A murine model of sepsis-induced AKI was established by cecal ligation and puncture (CLP). Mice undergoing CLP and immortalized proximal tubular epithelial human HK-2 cells that were exposed to lipopolysaccharide (LPS) were treated with recombinant KL, autophagy stimulator rapamycin (Rap), and autophagy suppressor 3-methyladenine (3-MA)...
2018: OncoTargets and Therapy
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/29422997/hucmsc-exosomes-delivered-14-3-3%C3%AE-enhanced-autophagy-via-modulation-of-atg16l-in-preventing-cisplatin-induced-acute-kidney-injury
#13
Haoyuan Jia, Wanzhu Liu, Bin Zhang, Juanjuan Wang, Peipei Wu, Nitin Tandra, Zhaofeng Liang, Cheng Ji, Lei Yin, Xinyuan Hu, Yongmin Yan, Fei Mao, Xu Zhang, Jing Yu, Wenrong Xu, Hui Qian
The clinical application of cisplatin is restricted by its side effects of nephrotoxicity. Human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-ex) have an important effect in tissue injury repair. Our previous work discovered that pretreatment with human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-ex) alleviated cisplatin-induced acute kidney injury (AKI) by activating autophagy both in vitro and in vivo . In this study, we further explored the mechanisms of hucMSC-ex in autophagy for preventing cisplatin-induced nephrotoxicity...
2018: American Journal of Translational Research
https://www.readbyqxmd.com/read/29367586/neutrophil-gelatinase-associated-lipocalin-attenuates-ischemia-reperfusion-injury-in-an-in-vitro-model-via-autophagy-activation
#14
Cai Yan, Tang Yuanjie, Xu Zhengqun, Chen Jiayan, Li Kongdan
BACKGROUND The aim of this study was to investigate the protective effects of neutrophil gelatinase-associated lipocalin (NGAL) on hypoxia/reoxygenation (H/R) induced acute kidney injury (AKI) in vitro. MATERIAL AND METHODS We used NRK-52E cells and H/R treatments to mimic ischemia/reperfusion injury (IRI) in vitro. Experimental groups were: the control group, the H/R group, the 3-methyladenine (3-MA)+H/R group, the NGAL (0.25, 0.5, and 1 ug/mL)+H/R group, and the NGAL (0.25, 0.5, 1 ug/mL)+3-MA+H/R group. After 24 hours of culture, cell proliferation was analyzed by CCK-8 assay...
January 25, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29361668/cutaneous-exposure-to-lewisite-causes-acute-kidney-injury-by-invoking-dna-damage-and-autophagic-response
#15
Ritesh Srivastava, Amie M Traylor, Changzhao Li, Wenguang Feng, Lingling Guo, Veena B Antony, Trenton R Schoeb, Anupam Agarwal, Mohammad Athar
Lewisite (2-chlorovinyldichloroarsine) is an organic and arsenical chemical warfare agent which was developed and weaponized during World Wars I/II. Stockpiles of lewisite still exist in many parts of the world and pose potential environmental and human health threat. Exposure to lewisite and similar chemicals causes intense cutaneous inflammatory response. However, morbidity and mortality in the exposed population is not only due to cutaneous damage but is also a result of systemic injury. Here, we provide data delineating the pathogenesis of acute kidney injury (AKI) following cutaneous exposure to lewisite and its analogue phenylarsine oxide (PAO) in a murine model...
January 17, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29358506/blockade-of-histone-deacetylase-6-protects-against-cisplatin-induced-acute-kidney-injury
#16
Jinhua Tang, Yingfeng Shi, Na Liu, Liuqing Xu, Xiujuan Zang, Peibin Li, Juanlian Zhang, Xiaoqing Zheng, Andong Qiu, Shougang Zhuang
Histone deacetylase 6 (HDAC6) has been shown to be involved in various pathological conditions, including cancer, neurodegenerative disorders and inflammatory diseases. Nonetheless, its specific role in drug-induced nephrotoxicity is poorly understood. Cisplatin (dichlorodiamino platinum) belongs to an inorganic platinum - fundamental chemotherapeutic drug utilized in the therapy of various solid malignant tumors. However, the use of cisplatin is extremely limited by obvious side effects, for instance bone marrow suppression and nephrotoxicity...
February 14, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29348412/influence-of-autophagy-on-acute-kidney-injury-in-a-murine-cecal-ligation-and-puncture-sepsis-model
#17
Satoshi Sunahara, Eizo Watanabe, Masahiko Hatano, Paul E Swanson, Takehiko Oami, Lisa Fujimura, Youichi Teratake, Takashi Shimazui, Chiwei Lee, Shigeto Oda
The role of autophagy in the maintenance of renal homeostasis during sepsis is not well understood. We therefore aimed to determine the influence of autophagy on kidney during sepsis using a murine sepsis model, i.e. cecal ligation and puncture (CLP). In CLP treated animals, the number of autolysosomes observed by electron microscopy increased over time. The number of autophagosomes in CLP animals decreased relative sham operated controls at 24 hrs after CLP, indicating that autophagy flux is already diminishing by that time...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29187371/effects-of-erythropoietin-receptor-activity-on-angiogenesis-tubular-injury-and-fibrosis-in-acute-kidney-injury-a-u-shaped-relationship
#18
Mingjun Shi, Brianna Flores, Peng Li, Nancy Gillings, Kathryn L McMillan, Jianfeng Ye, Lily June-Shen Huang, Sachdev S Sidhu, Yong-Ping Zhong, Maria T Grompe, Philip R Streeter, Orson W Moe, Ming Chang Hu
Erythropoietin receptor (EpoR) is widely expressed but its renoprotective action is unexplored. To examine the role of EpoR in vivo in the kidney, we induced acute kidney injury (AKI) by ischemia-reperfusion in mice with different EpoR bioactivities in the kidney. EpoR bioactivity was reduced by knock-in of wild type human EpoR, which is hypo-functional relative to murine EpoR, and a renal tubule-specific EpoR knockout. These mice had lower EPO/EpoR activity and lower autophagy flux in renal tubules. Upon AKI induction, they exhibited worse renal function and structural damage, and more apoptosis at the acute stage (< 7 days), and slower recovery with more tubulointerstitial fibrosis at the subacute stage (14 days)...
November 29, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29172924/pink1-prkn-park2-pathway-of-mitophagy-is-activated-to-protect-against-renal-ischemia-reperfusion-injury
#19
Chengyuan Tang, Hailong Han, Mingjuan Yan, Shiyao Zhu, Jing Liu, Zhiwen Liu, Liyu He, Jieqiong Tan, Yu Liu, Hong Liu, Lin Sun, Shaobin Duan, Youming Peng, Fuyou Liu, Xiao-Ming Yin, Zhuohua Zhang, Zheng Dong
Damaged or dysfunctional mitochondria are toxic to the cell by producing reactive oxygen species and releasing cell death factors. Therefore, timely removal of these organelles is critical to cellular homeostasis and viability. Mitophagy is the mechanism of selective degradation of mitochondria via autophagy. The significance of mitophagy in kidney diseases, including ischemic acute kidney injury (AKI), has yet to be established, and the involved pathway of mitophagy remains poorly understood. Here, we show that mitophagy is induced in renal proximal tubular cells in both in vitro and in vivo models of ischemic AKI...
February 17, 2018: Autophagy
https://www.readbyqxmd.com/read/29161706/endotoxin-effects-on-cardiac-and-renal-functions-and-cardiorenal-syndromes
#20
Grazia Maria Virzì, Anna Clementi, Alessandra Brocca, Claudio Ronco
Gram-negative sepsis is a major cause of morbidity and mortality in critical ill patients. Recent findings in molecular biology and in signaling pathways have enhanced our understanding of its pathogenesis and opened up opportunities of innovative therapeutic approaches. Endotoxin plays a pivotal role in the pathogenesis of multi-organ dysfunction in the setting of gram-negative sepsis. Indeed, heart and kidney impairments seem to be induced by the release of circulating pro-inflammatory and pro-apoptotic mediators triggered by endotoxin interaction with immune cells...
2017: Blood Purification
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