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Renal tubule cell autophagy

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https://www.readbyqxmd.com/read/29806072/deregulation-of-autophagy-under-hyperglycemic-conditions-is-dependent-on-increased-lysin63-ubiquitination-a-candidate-mechanism-in-the-progression-of-diabetic-nephropathy
#1
Paola Pontrelli, Annarita Oranger, Mariagrazia Barozzino, Chiara Divella, Francesca Conserva, Maria Grazia Fiore, Roberta Rossi, Massimo Papale, Giuseppe Castellano, Simona Simone, Luigi Laviola, Francesco Giorgino, Domenico Piscitelli, Anna Gallone, Loreto Gesualdo
Diabetic nephropathy patients (DN) are characterized by increased lysine63 ubiquitination (Lys63-Ub) at the tubular level. Autophagy is deregulated under diabetic conditions, even though the molecular mechanisms and the consequences of this alteration need to be elucidated. The aim of this study was to investigate the link between Lys63-Ub and autophagy in DN and the involvement of these two processes in tubular cell fate. Immunohistochemistry of beclin-1, LC3, and p62 on kidney biopsies highlighted increased protein expression of all these autophagic factors at the tubular level in DN compared to other nephritis...
May 27, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
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/29749806/rapamycin-induced-autophagy-protects-proximal-tubular-renal-cells-against-proteinuric-damage-through-the-transcriptional-activation-of-the-nerve-growth-factor-receptor-ngfr
#3
D Vizza, A Perri, G Toteda, S Lupinacci, I Perrotta, D Lofaro, F Leone, P Gigliotti, A La Russa, R Bonofiglio
Experimental evidence demonstrated that macroautophagy/autophagy exerts a crucial role in maintain renal cellular homeostasis and represents a protective mechanism against renal injuries. Interestingly, it has been demonstrated that in the human proximal tubular renal cell line, HK-2, the MTOR inhibitor rapamycin enhanced autophagy and mitigated the apoptosis damage induced by urinary protein overload. However, the underlying molecular mechanism has not yet been elucidated. In our study we demonstrated, for the first time, that in HK-2 cells, the exposure to low doses of rapamycin transactivated the NGFR promoter, leading to autophagic activation...
May 11, 2018: Autophagy
https://www.readbyqxmd.com/read/29665669/-effects-of-intermittent-hypoxia-exposure-on-renal-tubular-epithelial-cell-injury-and-autophagy-in-rats
#4
C Wang, J Tan, B Y Chen, Q Zhang
Objective: To investigate the effects of intermittent hypoxia (IH) exposure on renal tubular epithelial cell injury and autophagy in rats. Methods: A total of 12 Sprague Dawley (SD) rats were randomly divided into two groups: normal control (NC) group and IH group, with 6 rats in each group. An IH animal model was established to observe the effects of IH on renal tubular epithelial cell damage and autophagy in rats. Microalbumin (mAlb) was detected by immunoturbidimetry. Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1(KIM-1)in urine were assessed by enzyme-linked immunosorbent assay (ELISA) test...
March 27, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
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
#5
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...
June 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29575816/kidney-derived-c-kit-cells-possess-regenerative-potential
#6
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/29511793/calcifying-nanoparticles-induce-cytotoxicity-mediated-by-ros-jnk-signaling-pathways
#7
Jihua Wu, Zhiwei Tao, Yaoliang Deng, Quan Liu, Yunlong Liu, Xiaofeng Guan, Xiang Wang
Calcifying nanoparticles (CNPs) play an important role in kidney stone formation, but the mechanism(s) are unclear. CNPs were isolated and cultured from midstream urine of patients with kidney stones. CNP morphology and characteristics were examined by electron microscopy and electrophoresis analysis. Chemical composition was analyzed using energy-dispersive X-ray microanalysis and Western blotting. Human renal proximal convoluted tubule cell (HK-2) cultures were exposed to CNPs for 0, 12 and 72 h, and production of reactive oxygen species (ROS), mitochondrial membrane potential and apoptosis levels were evaluated...
March 6, 2018: Urolithiasis
https://www.readbyqxmd.com/read/29494565/albumin-overload-and-pink1-parkin-signaling-related-mitophagy-in-renal-tubular-epithelial-cells
#8
Jin Tan, Qi Xie, Shuling Song, Yuyang Miao, Qiang Zhang
BACKGROUND Albumin, as a major urinary protein component, is a risk factor for chronic kidney disease progression. Mitochondrial dysfunction is one of the main causes of albumin-induced proximal tubule cells injury. Mitophagy is considered as a pivotal protective mechanism for the elimination of dysfunctional mitochondria. The objective of this research was to determine whether albumin overload-induced mitochondrial dysfunction can activate PINK1/Parkin-mediated mitophagy in renal tubular epithelial cells (TECs)...
March 1, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29476062/histone-deacetylase-inhibitors-protect-against-cisplatin-induced-acute-kidney-injury-by-activating-autophagy-in-proximal-tubular-cells
#9
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/29425932/ablation-of-c-ebp-homologous-protein-attenuates-renal-fibrosis-after-ureteral-obstruction-by-reducing-autophagy-and-microtubule-disruption
#10
Mi Ra Noh, Chang-Hoon Woo, Mae-Ja Park, Jee In Kim, Kwon Moo Park
Fibrosis is an undesirable consequence of injury and a critical problem in many diseases. Recent studies have demonstrated an association of C/EBP homologous protein (CHOP) with fibrosis. We investigated the mechanism of CHOP in kidney fibrosis progression after unilateral ureteral obstruction (UUO) using Chop gene-deleted (Chop-/- ) mice and their wild-type littermates (Chop+/+ ). UUO-induced kidney fibrosis was reduced in the Chop-/- than Chop+/+ mice. After UUO, CHOP expression was detected in the cytosol and nucleus of distal tubule cells and collecting duct cells of the kidney...
May 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29425694/renal-fibrosis-primacy-of-the-proximal-tubule
#11
REVIEW
Leslie S Gewin
Tubulointerstitial fibrosis (TIF) is the hallmark of chronic kidney disease and best predictor of renal survival. Many different cell types contribute to TIF progression including tubular epithelial cells, myofibroblasts, endothelia, and inflammatory cells. Previously, most of the attention has centered on myofibroblasts given their central importance in extracellular matrix production. However, emerging data focuses on how the response of the proximal tubule, a specialized epithelial segment vulnerable to injury, plays a central role in TIF progression...
February 6, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29361668/cutaneous-exposure-to-lewisite-causes-acute-kidney-injury-by-invoking-dna-damage-and-autophagic-response
#12
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/29311680/inhibition-of-insulin-resistance-by-pge1-via-autophagy-dependent-fgf21-pathway-in-diabetic-nephropathy
#13
Wei Wei, Xing-Rong An, Shi-Jie Jin, Xiao-Xue Li, Ming Xu
Insulin resistance is a critical process in the initiation and progression of diabetic nephropathy (DN). Alprostadil (Prostaglandin E1, PGE1) had protective effects on renal function. However, it is unknown whether PGE1 inhibited insulin resistance in renal tubule epithelial cells via autophagy, which plays a protective role in DN against insulin resistance. Insulin resistance was induced by palmitic acid (PA) in human HK-2 cells, shown as the decrease of insulin-stimulated AKT phosphorylation, glucose transporter-4 (GLUT4), glucose uptake and enhanced phosphorylation of insulin receptor substrate 1(IRS-1) at site serine 307 (pIRS-1ser307) and downregulated expression of IRS-1...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29234448/aristolochic-acid-induced-autophagy-promotes-epithelial-to-myofibroblast-transition-in-human-renal-proximal-tubule-epithelial-cells
#14
Yu-Lin Man, Hong-Liang Rui, Yi-Pu Chen, Guo-Qin Wang, Li-Jun Sun, Hong Cheng
Autophagy plays an essential role in cellular homeostasis in kidney. Previous studies have found that aristolochic acid (AA) can induce autophagy of renal tubular epithelial cells and epithelial-to-myofibroblast transition (EMT). However, the relationship between AA-induced autophagy and EMT is unclear. Our results showed that, after AA stimulation, the appearance of autophagy preceded EMT. Autophagy of HKC cells began to increase gradually from the 3rd hour, reached the peak at 12th hour, and then weakened gradually until 36th hour; the EMT process of HKC continued to increase from 6th hour to 36th hour after AA stimulation...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
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
#15
Mingjun Shi, Brianna Flores, Peng Li, Nancy Gillings, Kathryn L McMillan, Jianfeng Ye, Lily Jun-Shen Huang, Sachdev S Sidhu, Yong-Ping Zhong, Maria T Grompe, Philip R Streeter, Orson W Moe, Ming Chang Hu
The 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 knockin of wild-type human EpoR, which is hypofunctional 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, more apoptosis at the acute stage (<7 days), and slower recovery with more tubulointerstitial fibrosis at the subacute stage (14 days)...
April 1, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29063120/-advances-in-mechanism-of-autophagy-in-renal-tubular-injury
#16
Fan Yin, Li-Min Lu
Autophagy is a lysosome-dependent degradation process that eliminates damaged macromolecular proteins and aging organelles to maintain intracellular homeostasis. Autophagy is observed in almost all eukaryotic cells and plays important roles in many cellular physiological processes, including the cell proliferation and growth, cellular functional alteration and phenotypical transition. Renal tubule is an important target for renal injury under different pathological conditions. Following the discoveries of the molecular basis of autophagy, accumulated lines of evidence have indicated that autophagy dysfunction in tubule is involved in the pathogenesis of many renal diseases...
October 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/28886014/downregulation-of-autophagy-is-associated-with-severe-ischemia-reperfusion-induced-acute-kidney-injury-in-overexpressing-c-reactive-protein-mice
#17
Ao Bian, Mingjun Shi, Brianna Flores, Nancy Gillings, Peng Li, Shirley Xiao Yan, Beth Levine, Changying Xing, Ming Chang Hu
C-reactive protein (CRP), was recently reported to be closely associated with poor renal function in patients with acute kidney injury (AKI), but whether CRP is pathogenic or a mere biomarker in AKI remains largely unclear. Impaired autophagy is known to exacerbate renal ischemia-reperfusion injury (IRI). We examined whether the pathogenic role of CRP in AKI is associated with reduction of autophagy. We mated transgenic rabbit CRP over-expressing mice (Tg-CRP) with two autophagy reporter mouse lines, Tg-GFP-LC3 mice (LC3) and Tg-RFP-GFP-LC3 mice (RG-LC3) respectively to generate Tg-CRP-GFP-LC3 mice (PLC3) and Tg-CRP-RFP-GFP-LC3 mice (PRG-LC3)...
2017: PloS One
https://www.readbyqxmd.com/read/28813167/lipophagy-maintains-energy-homeostasis-in-the-kidney-proximal-tubule-during-prolonged-starvation
#18
Satoshi Minami, Takeshi Yamamoto, Yoshitsugu Takabatake, Atsushi Takahashi, Tomoko Namba, Jun Matsuda, Tomonori Kimura, Jun-Ya Kaimori, Isao Matsui, Takayuki Hamano, Hiroaki Takeda, Masatomo Takahashi, Yoshihiro Izumi, Takeshi Bamba, Taiji Matsusaka, Fumio Niimura, Yoshitaka Isaka
Macroautophagy/autophagy is a self-degradation process that combats starvation. Lipids are the main energy source in kidney proximal tubular cells (PTCs). During starvation, PTCs increase fatty acid (FA) uptake, form intracellular lipid droplets (LDs), and hydrolyze them for use. The involvement of autophagy in lipid metabolism in the kidney remains largely unknown. Here, we investigated the autophagy-mediated regulation of renal lipid metabolism during prolonged starvation using PTC-specific Atg5-deficient (atg5-TSKO) mice and an in vitro serum starvation model...
October 3, 2017: Autophagy
https://www.readbyqxmd.com/read/28705935/forkhead-box-o3-foxo3-regulates-kidney-tubular-autophagy-following-urinary-tract-obstruction
#19
COMPARATIVE STUDY
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...
August 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28465352/cystinosin-the-small-gtpase-rab11-and-the-rab7-effector-rilp-regulate-intracellular-trafficking-of-the-chaperone-mediated-autophagy-receptor-lamp2a
#20
Jinzhong Zhang, Jennifer L Johnson, Jing He, Gennaro Napolitano, Mahalakshmi Ramadass, Celine Rocca, William B Kiosses, Cecilia Bucci, Qisheng Xin, Evripidis Gavathiotis, Ana María Cuervo, Stephanie Cherqui, Sergio D Catz
The lysosomal storage disease cystinosis, caused by cystinosin deficiency, is characterized by cell malfunction, tissue failure, and progressive renal injury despite cystine-depletion therapies. Cystinosis is associated with defects in chaperone-mediated autophagy (CMA), but the molecular mechanisms are incompletely understood. Here, we show CMA substrate accumulation in cystinotic kidney proximal tubule cells. We also found mislocalization of the CMA lysosomal receptor LAMP2A and impaired substrate translocation into the lysosome caused by defective CMA in cystinosis...
June 23, 2017: Journal of Biological Chemistry
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