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Renal tubule cell autophagy

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https://www.readbyqxmd.com/read/27878656/mille-modis-morimur-we-die-in-a-thousand-ways
#1
Gaspar Banfalvi
Dying cells subjected to apoptotic programs are engulfed by neighboring cells or by professional phagocytes, without inflammation or immunological reactions in the tissue where apoptosis takes place. Apoptotic cells release danger-associated project signals to their neighbours, through different molecular patterns, stimulate antigen production and immune responses. Microenvironmental effects with several functional consequences indicate that cell death is a complex process and may take place in several ways...
November 23, 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27582098/proteinuria-causes-dysfunctional-autophagy-in-the-proximal-tubule
#2
Angela C Nolin, Ryan M Mulhern, Maria V Panchenko, Anna Pisarek-Horowitz, Zhiyong Wang, Orian Shirihai, Steven C Borkan, Andrea Havasi
Proteinuria is a major risk factor for chronic kidney disease progression. Furthermore, exposure of proximal tubular epithelial cells to excess albumin promotes tubular atrophy and fibrosis, key predictors of progressive organ dysfunction. However, the link between proteinuria and tubular damage is unclear. We propose that pathological albumin exposure impairs proximal tubular autophagy, an essential process for recycling damaged organelles and toxic intracellular macromolecules. In both mouse primary proximal tubule and immortalized human kidney cells, albumin exposure decreased the number of autophagosomes, visualized by the autophagosome-specific fluorescent markers monodansylcadaverine and GFP-LC3, respectively...
December 1, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27511942/ethylmercury-induced-oxidative-and-endoplasmic-reticulum-stress-mediated-autophagic-cell-death-involvement-of-autophagosome-lysosome-fusion-arrest
#3
Ji-Yoon Choi, Nam-Hee Won, Jung-Duck Park, Sinae Jang, Chi-Yong Eom, Yongseok Choi, Young In Park, Mi-Sook Dong
Ethylmercury (EtHg) is derived from the degradation of thimerosal, the most widely used organomercury compound. In this study, EtHg-induced toxicity and autophagy in the mouse kidney was observed and then the mechanism of toxicity was explored in vitro in HK-2 cells. Low doses of EtHg induced autophagy without causing any histopathological changes in mouse kidneys. However, mice treated with high doses of EtHg exhibited severe focal tubular cell necrosis of the proximal tubules with autophagy. EtHg dose-dependently increased the production of reactive oxygen species, reduced the mitochondrial membrane potential, activated the unfolded protein response, and increased cytosolic Ca(2+) levels in HK-2 cells...
August 10, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/27465995/delayed-treatment-with-fenofibrate-protects-against-high-fat-diet-induced-kidney-injury-in-mice-the-possible-role-of-ampk-autophagy
#4
Minji Sohn, Keumji Kim, Md Jamal Uddin, Gayoung Lee, Inah Hwang, Hyeji Kang, Hyunji Kim, Jung Hwa Lee, Hunjoo Ha
Fenofibrate activates not only peroxisome proliferator-activated receptor α (PPARα) but also adenosine monophosphate-activated protein kinase (AMPK). AMPK-mediated cellular responses protect kidney from high-fat diet (HFD)-induced injury, and autophagy resulting from AMPK activation has been regarded as a stress-response mechanism. Thus, the present study examined the role of AMPK and autophagy in the renotherapeutic effects of fenofibrate. C57BL/6J mice were divided into 3 groups: normal diet (ND), HFD, and HFD+fenofibrate (HFD+FF)...
July 27, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27304991/atg5-mediated-autophagy-deficiency-in-proximal-tubules-promotes-cell-cycle-g2-m-arrest-and-renal-fibrosis
#5
Huiyan Li, Xuan Peng, Yating Wang, Shirong Cao, Liping Xiong, Jinjin Fan, Yihan Wang, Shougang Zhuang, Xueqing Yu, Haiping Mao
Macroautophagy/autophagy protects against cellular stress. Renal sublethal injury-triggered tubular epithelial cell cycle arrest at G2/M is associated with interstitial fibrosis. However, the role of autophagy in renal fibrosis is elusive. Here, we hypothesized that autophagy activity in tubular epithelial cells is pivotal for inhibition of cell cycle G2/M arrest and subsequent fibrogenic response. In both renal epithelial cells stimulated by angiotensin II (AGT II) and the murine kidney after unilateral ureteral obstruction (UUO), we observed that occurrence of autophagy preceded increased production of COL1 (collagen, type I)...
September 2016: Autophagy
https://www.readbyqxmd.com/read/27153058/autophagy-innate-immunity-and-tissue-repair-in-acute-kidney-injury
#6
REVIEW
Pu Duann, Elias A Lianos, Jianjie Ma, Pei-Hui Lin
Kidney is a vital organ with high energy demands to actively maintain plasma hemodynamics, electrolytes and water homeostasis. Among the nephron segments, the renal tubular epithelium is endowed with high mitochondria density for their function in active transport. Acute kidney injury (AKI) is an important clinical syndrome and a global public health issue with high mortality rate and socioeconomic burden due to lack of effective therapy. AKI results in acute cell death and necrosis of renal tubule epithelial cells accompanied with leakage of tubular fluid and inflammation...
2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27123926/persistent-activation-of-autophagy-in-kidney-tubular-cells-promotes-renal-interstitial-fibrosis-during-unilateral-ureteral-obstruction
#7
Man J Livingston, Han-Fei Ding, Shuang Huang, Joseph A Hill, Xiao-Ming Yin, Zheng Dong
Renal fibrosis is the final, common pathway of end-stage renal disease. Whether and how autophagy contributes to renal fibrosis remains unclear. Here we first detected persistent autophagy in kidney proximal tubules in the renal fibrosis model of unilateral ureteral obstruction (UUO) in mice. UUO-associated fibrosis was suppressed by pharmacological inhibitors of autophagy and also by kidney proximal tubule-specific knockout of autophagy-related 7 (PT-Atg7 KO). Consistently, proliferation and activation of fibroblasts, as indicated by the expression of ACTA2/α-smooth muscle actin and VIM (vimentin), was inhibited in PT-Atg7 KO mice, so was the accumulation of extracellular matrix components including FN1 (fibronectin 1) and collagen fibrils...
June 2, 2016: Autophagy
https://www.readbyqxmd.com/read/26990086/autophagy-limits-endotoxemic-acute-kidney-injury-and-alters-renal-tubular-epithelial-cell-cytokine-expression
#8
Jeremy S Leventhal, Jie Ni, Morgan Osmond, Kyung Lee, G Luca Gusella, Fadi Salem, Michael J Ross
Sepsis related acute kidney injury (AKI) is a common in-hospital complication with a dismal prognosis. Our incomplete understanding of disease pathogenesis has prevented the identification of hypothesis-driven preventive or therapeutic interventions. Increasing evidence in ischemia-reperfusion and nephrotoxic mouse models of AKI support the theory that autophagy protects renal tubular epithelial cells (RTEC) from injury. However, the role of RTEC autophagy in septic AKI remains unclear. We observed that lipopolysaccharide (LPS), a mediator of gram-negative bacterial sepsis, induces RTEC autophagy in vivo and in vitro through TLR4-initiated signaling...
2016: PloS One
https://www.readbyqxmd.com/read/26924060/autophagy-in-acute-kidney-injury
#9
REVIEW
Gur P Kaushal, Sudhir V Shah
Autophagy is a conserved multistep pathway that degrades and recycles damaged organelles and macromolecules to maintain intracellular homeostasis. The autophagy pathway is upregulated under stress conditions including cell starvation, hypoxia, nutrient and growth-factor deprivation, endoplasmic reticulum stress, and oxidant injury, most of which are involved in the pathogenesis of acute kidney injury (AKI). Recent studies demonstrate that basal autophagy in the kidney is vital for the normal homeostasis of the proximal tubules...
April 2016: Kidney International
https://www.readbyqxmd.com/read/26909499/altered-mtor-signalling-in-nephropathic-cystinosis
#10
Ekaterina A Ivanova, Lambertus P van den Heuvel, Mohamed A Elmonem, Humbert De Smedt, Ludwig Missiaen, Anna Pastore, Djalila Mekahli, Greet Bultynck, Elena N Levtchenko
Lysosomes play a central role in regulating autophagy via activation of mammalian target of rapamycin complex 1 (mTORC1). We examined mTORC1 signalling in the lysosomal storage disease nephropathic cystinosis (MIM 219800), in which accumulation of autophagy markers has been previously demonstrated. Cystinosis is caused by mutations in the lysosomal cystine transporter cystinosin and initially affects kidney proximal tubules causing renal Fanconi syndrome, followed by a gradual development of end-stage renal disease and extrarenal complications...
May 2016: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/26869517/cancer-drug-troglitazone-stimulates-the-growth-and-response-of-renal-cells-to-hypoxia-inducible-factors
#11
Mary Taub
Troglitazone has been used to suppress the growth of a number of tumors through apoptosis and autophagy. However, previous in vitro studies have employed very high concentrations of troglitazone (≥10(-5) M) in order to elicit growth inhibitory effects. In this report, when employing lower concentrations of troglitazone in defined medium, troglitazone was observed to stimulate the growth of primary renal proximal tubule (RPT) cells. Rosiglitazone, like troglitazone, is a thiazolidinedione (TZD) that is known to activate Peroxisome Proliferator Activated Receptor Υ (PPARΥ)...
March 11, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/26840285/a-silac-based-approach-elicits-the-proteomic-responses-to-vancomycin-associated-nephrotoxicity-in-human-proximal-tubule-epithelial-hk-2-cells
#12
Zhi-Ling Li, Shu-Feng Zhou
Vancomycin, a widely used antibiotic, often induces nephrotoxicity, however, the molecular targets and underlying mechanisms of this side effect remain unclear. The present study aimed to examine molecular interactome and analyze the signaling pathways related to the vancomycin-induced nephrotoxicity in human proximal tubule epithelial HK-2 cells using the stable isotope labeling by amino acids in cell culture (SILAC) approach. The quantitative proteomic study revealed that there were at least 492 proteins interacting with vancomycin and there were 290 signaling pathways and cellular functions potentially regulated by vancomycin in HK-2 cells...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/26761120/the-yin-and-yang-of-autophagy-in-acute-kidney-injury
#13
Anette Melk, Arpita Baisantry, Roland Schmitt
Antagonizing the strongly activated pathway of autophagy in renal ischemic injury has been associated with poor outcome. In our recent study we used mice with a selective deletion of Atg5 in the S3 proximal tubule segment, which is most susceptible to ischemic damage. In line with the notion that autophagy is a prosurvival mechanism our studies revealed an early accelerated cell death of heavily damaged tubular cells in the S3 segment of these mice. Interestingly, this expedited loss of cells was associated with better long-term outcome as reflected by less inflammation, improved tubular repair, and function and reduced accumulation of senescent cells...
2016: Autophagy
https://www.readbyqxmd.com/read/26534923/megalin-mediated-tubuloglomerular-alterations-in-high-fat-diet-induced-kidney-disease
#14
Shoji Kuwahara, Michihiro Hosojima, Reika Kaneko, Hiroyuki Aoki, Daisuke Nakano, Taiji Sasagawa, Hideyuki Kabasawa, Ryohei Kaseda, Ryota Yasukawa, Tomomi Ishikawa, Akiyo Suzuki, Hiroyoshi Sato, Shun Kageyama, Takahiro Tanaka, Nobutaka Kitamura, Ichiei Narita, Masaaki Komatsu, Akira Nishiyama, Akihiko Saito
Obesity, an important risk factor for metabolic syndrome (MetS) and cardiovascular disease, is often complicated by CKD, which further increases cardiovascular risk and causes ESRD. To elucidate the mechanism underlying this relationship, we investigated the role of the endocytic receptor megalin in proximal tubule epithelial cells (PTECs). We studied a high-fat diet (HFD)-induced obesity/MetS model using kidney-specific mosaic megalin knockout (KO) mice. Compared with control littermates fed a normal-fat diet, control littermates fed an HFD for 12 weeks showed autolysosomal dysfunction with autophagy impairment and increased expression of hypertrophy, lipid peroxidation, and senescence markers in PTECs of the S2 segment, peritubular capillary rarefaction with localized interstitial fibrosis, and glomerular hypertrophy with mesangial expansion...
July 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/26384705/radiocontrast-induced-nephropathy-is-attenuated-by-autophagy-through-regulation-of-apoptosis-and-inflammation
#15
Gang Jee Ko, So Yeon Bae, Yu-Ah Hong, Heui Jung Pyo, Young Joo Kwon
Radiocontrast-induced nephropathy (RCN) is the third most common cause of acute renal failure among inpatients. Although the number of patients undergoing exams using radiocontrast is increasing, little progress has been made for RCN treatment. The pathophysiology of RCN is known as tubular injury due to oxidative stress. As autophagy regulates cellular damage under stressful conditions, we investigated the role of autophagy in RCN. RCN was induced in male C57BL/6 J mice by intraperitoneal injection of iohexol, and 3-methyladenine (3-MA) was used as an autophagy inhibitor...
July 2016: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/26344726/the-epigenetic-regulation-of-podocyte-function-in-diabetes
#16
REVIEW
Syamantak Majumder, Andrew Advani
Chronic hyperglycemia early in the course of diabetes confers a sustained increase in the risk of complications development. In recent years, efforts to understand the molecular basis for this "metabolic memory" have focused on epigenetic mechanisms as a means by which transient high glucose can cause persistent and propagated changes in cell function. For instance, in vascular endothelial cells, smooth muscle cells and peripheral blood cells, temporary exposure to high glucose causes changes in epigenetic marks that promote a shift towards a pro-inflammatory phenotype...
November 2015: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/26079813/activation-of-autophagy-and-nucleotide-binding-domain-leucine-rich-repeat-containing-like-receptor-family-pyrin-domain-containing-3-inflammasome-during-leishmania-infantum-associated-glomerulonephritis
#17
Kevin J Esch, Robert G Schaut, Ian M Lamb, Gwendolyn Clay, Ádila L Morais Lima, Paulo R P do Nascimento, Elizabeth M Whitley, Selma M B Jeronimo, Fayyaz S Sutterwala, Joseph S Haynes, Christine A Petersen
Chronic kidney disease is a major contributor to human and companion animal morbidity and mortality. Renal complications are sequelae of canine and human visceral leishmaniasis (VL). Despite the high incidence of infection-mediated glomerulonephritis, little is known about pathogenesis of VL-associated renal disease. Leishmania infantum-infected dogs are a naturally occurring model of VL-associated glomerulonephritis. Membranoproliferative glomerulonephritis type I [24 of 25 (96%)], with interstitial lymphoplasmacytic nephritis [23 of 25 (92%)], and glomerular and interstitial fibrosis [12 of 25 (48%)] were predominant lesions...
August 2015: American Journal of Pathology
https://www.readbyqxmd.com/read/26052900/rapamycin-protects-against-gentamicin-induced-acute-kidney-injury-via-autophagy-in-mini-pig-models
#18
Jing Cui, Xue-Yuan Bai, Xuefeng Sun, Guangyan Cai, Quan Hong, Rui Ding, Xiangmei Chen
Gentamicin may cause acute kidney injury. The pathogenesis of gentamicin nephrotoxicity is unclear. Autophagy is a highly conserved physiological process involved in removing damaged or aged biological macromolecules and organelles from the cytoplasm. The role of autophagy in the pathogenesis of gentamicin nephrotoxicity is unclear. The miniature pigs are more similar to humans than are those of rodents, and thus they are more suitable as human disease models. Here we established the first gentamicin nephrotoxicity model in miniature pigs, investigated the role of autophagy in gentamicin-induced acute kidney injury, and determined the prevention potential of rapamycin against gentamicin-induced oxidative stress and renal dysfunction...
2015: Scientific Reports
https://www.readbyqxmd.com/read/25962073/small-heat-shock-protein-beta-1-hspb1-is-upregulated-and-regulates-autophagy-and-apoptosis-of-renal-tubular-cells-in-acute-kidney-injury
#19
Tatsuki Matsumoto, Madoka Urushido, Haruna Ide, Masayuki Ishihara, Kazu Hamada-Ode, Yoshiko Shimamura, Koji Ogata, Kosuke Inoue, Yoshinori Taniguchi, Takafumi Taguchi, Taro Horino, Shimpei Fujimoto, Yoshio Terada
BACKGROUND: Heat shock protein beta-1 (HSPB1, also known as HSP27) is a small heat shock protein involved in many cellular processes and reportedly protects cells against oxidative stress. Autophagy protects cells from many types of stress and is thought to play a key role in preventing stress in acute kidney injury (AKI). However, little is known about the role of HSPB1 in autophagy and apoptosis in the pathogenesis of AKI. METHODS: We used a rat ischemia/reperfusion AKI model and cultured renal tubular cells as an in vitro model...
2015: PloS One
https://www.readbyqxmd.com/read/25760322/telomerase-deficiency-delays-renal-recovery-in-mice-after-ischemia-reperfusion-injury-by-impairing-autophagy
#20
Huifang Cheng, Xiaofeng Fan, William E Lawson, Paisit Paueksakon, Raymond C Harris
The aged population suffers increased morbidity and higher mortality in response to episodes of acute kidney injury (AKI). Aging is associated with telomere shortening, and both telomerase reverse transcriptase (TerT) and RNA (TerC) are essential to maintain telomere length. To define a role of telomerase deficiency in susceptibility to AKI, we used ischemia/reperfusion injury in wild-type mice or mice with either TerC or TerT deletion. Injury induced similar renal impairment at day 1 in each genotype, as assessed by azotemia, proteinuria, acute tubular injury score, and apoptotic tubular epithelial cell index...
July 2015: Kidney International
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