DOCSLIB.ORG

Cardiac Inflammation After Ischemia- Reperfusion of the Kidney: Role of the Sympathetic Nervous System and the Renin-Angiotensin System

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Cardiac Inflammation After Ischemia- Reperfusion of the Kidney: Role of the Sympathetic Nervous System and the Renin-Angiotensin System Cellular Physiology Cell Physiol Biochem 2019;53:587-605 DOI: 10.33594/00000015910.33594/000000159 © 2019 The Author(s).© 2019 Published The Author(s) by and Biochemistry Published online: 20 September 2019 Cell Physiol BiochemPublished Press GmbH&Co. by Cell Physiol KG Biochem 587 Press GmbH&Co. KG, Duesseldorf PanicoAccepted: et al.:12 SeptemberCardiac Inflammation 2019 After Renal Ischemiawww.cellphysiolbiochem.com This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 Interna- tional License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission. Original Paper Cardiac Inflammation after Ischemia- Reperfusion of the Kidney: Role of the Sympathetic Nervous System and the Renin-Angiotensin System Karine Panicoa Mariana V. Abrahãoa Mayra Trentin-Sonodaa,b Humberto Muzi-Filhoc,d Adalberto Vieyrac,d,e,f Marcela S. Carneiro-Ramosa aCenter for Natural and Human Sciences, Federal University of ABC, Santo André, São Paulo, Brazil, bCellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada, cCarlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil, dNational Center of Structural Biology and Bioimaging/CENABIO, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil, eNational Institute in Science and Technology for Regenerative Medicine/REGENERA, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil, fGraduate Program in Translational Biomedicine/BIOTRANS, Grande Rio University, Duque de Caxias, Brazil Key Words Cardiac hypertrophy • Inflammatory cytokines • Renal ischemia/reperfusion • Renin-angiotensin system • Sympathetic nervous system Abstract Background/Aims: To investigate the role of the sympathetic nervous system (SNS) and renin- angiotensin system (RAS) in renal ischemia/reperfusion-induced (I/R) cardiac inflammatory profile.Methods: Left kidney ischemia was induced in male C57BL/6 mice for 60 min, followed by reperfusion for 12 days, and treatment with or without atenolol, losartan, or enalapril. The expression of vimentin in kidney and atrial natriuretic factor (ANF) in the heart has been investigated by RT-PCR. In cardiac tissue, levels of β1-adrenoreceptors, adenylyl cyclase, cyclic AMP-dependent protein kinase (PKA), noradrenaline, adrenaline (components of SNS), type 1 angiotensin II receptors (AT1R), angiotensinogen/Ang II and renin (components of RAS) have been measured by Western blotting and HPLC analysis. A panel of cytokines – tumour necrosis factor (TNF-a), interleukin IL-6, and interferon gamma (IFN-g) – was selected as cardiac inflammatory markers.Results: Renal vimentin mRNA levels increased by >10 times in I/R mice, indicative of kidney injury. ANF, a marker of cardiac lesion, increased after renal I/R, the values being restored to the level of Sham group after atenolol or enalapril treatment. The cardiac inflammatory profile was confirmed by the marked increase in the levels of mRNAs of TNF-a, IL-6, and IFN-g. Atenolol and losartan reversed the upregulation of TNF-a expression, whereas enalapril restored IL-6 levels to Sham levels; both atenolol and enalapril normalized Marcela S. Carneiro-Ramos Center for Natural and Human Sciences, Federal University of ABC Santo André, São Paulo (Brazil) E-Mail [email protected] Cellular Physiology Cell Physiol Biochem 2019;53:587-605 DOI: 10.33594/000000159 © 2019 The Author(s). Published by and Biochemistry Published online: 20 September 2019 Cell Physiol Biochem Press GmbH&Co. KG 588 Panico et al.: Cardiac Inflammation After Renal Ischemia g IFN- levels. I/R mice showed upregulation of β1-adrenoreceptors, adenylyl cyclase, PKA and noradrenaline. Renal I/R increased cardiac levels of AT1R, which decreased after losartan or enalapril treatment. Renin expression also increased, with the upregulation returning to Sham levels after treatment with SNS and RAS blockers. Angiotensinogen/Ang II levels in heart were unaffected by renal I/R, but they were significantly decreased after treatment with losartan and enalapril, whereas increase in renin levels decreased. Conclusion: Renal I/R-induced cardiac inflammatory events provoked by the simultaneous upregulation of SNS and RAS in the heart, possibly underpin the mechanism involved in the development of cardiorenal syndrome. © 2019 The Author(s). Published by Cell Physiol Biochem Press GmbH&Co. KG Introduction Close physiological and physio-pathological relationships between the kidney and heart are found that share several functions maintaining homeostasis [1]. Cardiorenal syndrome is characterized by different clinical conditions, with an overlap of cardiac and renal dysfunctions. One subtype of this pathology involves cardiac hypertrophy and failure after acute renal injury (AKI) [1]. AKI frequently leads to the development of chronic kidney disease, and may be associated with ischemia followed by reperfusion (I/R). Ischemia 2 supply [2]. restrictstarget the renal heart, blood and flow,promote whereas cardiovascular reperfusion alterations restores thefollowing circulation the involvementand O of the immuneIschemic system renal damage [3]. promotes the release of different inflammatory cytokines that mainly complement system, etc.) is a non-traditional risk factor in cardiovascular diseases. Recently, Inflammation, a systemic condition mediated by multiple factors (cytokines, markershowever, andischemia, outcomes infection has beenand uremic documented milieu arein patientsknown to with stimulate chronic several kidney inflammatory disease [5- components in both the kidney and heart [4, 5]. An association between inflammatory 7]. Inflammation may, therefore, serve as a crucial link between increased cardiovascular risk Anand important kidney disease. role of Nevertheless, interleukin-6 the(IL-6) direct in the involvement molecular ofmechanisms immune or underlying inflammation the mediated damage to the pathogenesis of cardiorenal syndromes requires confirmation [8]. the sympathetic nervous system (SNS). Moreover, endogenous catecholamines present in immuneinitiation cells of hypertrophy play a central has role been in the identified crosstalk [9], between a process the involvingSNS and immune the participation system [10- of 14]. Trentin-Sonoda et al. [15] showed the participation of cytokines in cardiac lesions after renal I/R in mice. The evidence suggests an association between changes in the components of the renin-angiotensin system (RAS), levels of angiotensinogen II [16, 17], and cytokines including[18], with atrialincreased natriuretic cardiac factormass and(ANF) deleterious and acute cardiac cardiac remodelling lesions have [19-21]. been In reported the last [22-25].2 decades, Of thespecial relationship interest is between that important inflammatory direct andcytokines, indirect cardiac effects natriureticof RAS exist, factors, likely in the heart [16, 17]. mediatedWe also by foundlocal Ang – with II and the baroreflex, use of transthoracic respectively, echocardiography, which enhance SNS electrocardiogram activity and action potential recording in the left ventricle – that renal I/R provoked cardiac hypertrophy, increased cardiac wall, augmented myocyte width, and intense electric remodelling [15]. I/R [15] targets the heart and alters local RAS and SNS, underpinning the mechanism of a The leading hypothesis herein is that the systemic inflammatory response elicited by renal the observation that the b-adrenergic stimulus increases a macrophage-mediated immune responsePKA-mediated in the dysregulation presence of cAMP of the as cardiac the central cytokine mediator profile. [26, Support 27]. With for this this hypothesis hypothesis as is a 1 receptors (AT1R)) and enalapril (an inhibitor of the angiotensin converting enzyme (ACE)) tobasis, target we RAS.have Atenolol, investigated a blocker the responses of b1 to losartan (a specific1-AR) was antagonist used to inhibitof the Ang SNS. II type -adrenoceptors (β Cellular Physiology Cell Physiol Biochem 2019;53:587-605 DOI: 10.33594/000000159 © 2019 The Author(s). Published by and Biochemistry FigurePublished 1 online: 20 September 2019 Cell Physiol Biochem Press GmbH&Co. KG 589 Panico et al.: Cardiac Inflammation After Renal Ischemia Materials and Methods I/R Groups (60 min oclusion) Losartan (10 mg/kg d.w) Animals Enalapril (40 mg/kg d.w) All surgical procedures and 0 DAYS OF REPERFUSION 5 7 11 12 protocols abided by the Ethical Principles in Animal Research Atenolol (10 mg/kg i.p) Sham Groups Sacrifice set forth by the Brazilian College (No oclusion) of Animal Experimentation, and were approved by the Fig. 1. Flow chart showing chirurgical and pharmacological Federal University of ABC Ethics interventions in the Sham and I/R groups from the ischemia (or not) Committee for Animal Research 1 administration.on day zero until sacrifice after 12 days of reperfusion (horizontal (029/2013 and 030/2013). Male gray bar). Abbreviations: d.w, dissolved in water; i.p, intraperitoneal SãoC57BL/6 Paulo J University,mice, 8-week-old Institute (22– of Table 1. Primer sequences used for gene expression analysis Biomedical28 g), were Sciences obtained (São from Paulo, the Brazil). Mice were housed in a temperature and light-controlled environment (24°C; 12/12-h light/dark cycle), and had free Ǧα access to standard mice chow Ǧ͸ Ǧγ (Purina Agribands) and water ͳ β Ǧ until
Load more

Recommended publications
  • Ischemia-Reperfusion Injury Epithelial-Expressed Nlrp3 in Renal An
    An Inflammasome-Independent Role for Epithelial-Expressed Nlrp3 in Renal Ischemia-Reperfusion Injury This information is current as Alana A. Shigeoka, James L. Mueller, Amanpreet Kambo, of September 30, 2021. John C. Mathison, Andrew J. King, Wesley F. Hall, Jean da Silva Correia, Richard J. Ulevitch, Hal M. Hoffman and Dianne B. McKay J Immunol 2010; 185:6277-6285; Prepublished online 20 October 2010; Downloaded from doi: 10.4049/jimmunol.1002330 http://www.jimmunol.org/content/185/10/6277 References This article cites 62 articles, 15 of which you can access for free at: http://www.jimmunol.org/ http://www.jimmunol.org/content/185/10/6277.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 30, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts Errata An erratum has been published regarding this article. Please see next page or: /content/186/3/1880.full.pdf The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2010 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606.
    [Show full text]
  • Ischemia Regulates NK Cell Recruitment in Kidney TLR2
    TLR2 Signaling in Tubular Epithelial Cells Regulates NK Cell Recruitment in Kidney Ischemia−Reperfusion Injury This information is current as Hye J. Kim, Jong S. Lee, Ahra Kim, Sumi Koo, Hee J. Cha, of September 29, 2021. Jae-A Han, Yoonkyung Do, Kyung M. Kim, Byoung S. Kwon, Robert S. Mittler, Hong R. Cho and Byungsuk Kwon J Immunol 2013; 191:2657-2664; Prepublished online 31 July 2013; doi: 10.4049/jimmunol.1300358 Downloaded from http://www.jimmunol.org/content/191/5/2657 Supplementary http://www.jimmunol.org/content/suppl/2013/07/31/jimmunol.130035 Material 8v1.DC1 http://www.jimmunol.org/ References This article cites 97 articles, 15 of which you can access for free at: http://www.jimmunol.org/content/191/5/2657.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision by guest on September 29, 2021 • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2013 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606.
    [Show full text]
  • Inducible and Endothelial Nitric Oxide Synthase Distribution and Expression with Hind Limb Per-Conditioning of the Rat Kidney
    Experimental research Nephrology Inducible and endothelial nitric oxide synthase distribution and expression with hind limb per-conditioning of the rat kidney Zahra Sedaghat1,2, Mehri Kadkhodaee2, Behjat Seifi2, Eisa Salehi3 1Department of Physiology, School of Medicine, Bushehr University of Medical Corresponding author: Sciences, Bushehr, Iran Zahra Sedaghat 2Department of Physiology, School of Medicine, Tehran University of Medical Department Sciences, Tehran, Iran of Physiology 3Department of Immunology, School of Medicine, Tehran University of Medical School of Medicine Sciences, Tehran, Iran Bushehr University of Medical Sciences Submitted: 1 August 2016 Bushehr 7514633341 Accepted: 5 March 2017 Iran Phone: +98 9171865245 Arch Med Sci 2019; 15 (4): 1081–1091 Fax: +987733320657 DOI: https://doi.org/10.5114/aoms.2019.85651 E-mail: z.sedaghat@bpums. Copyright © 2019 Termedia & Banach ac.ir Abstract Introduction: We recently reported that a series of brief hind limb ischemia and reperfusion (IR) at the beginning of renal ischemia (remote per-condi- tioning – RPEC) significantly attenuated the ischemia/reperfusion-induced acute kidney injury. In the present study, we investigated whether the nitric oxide synthase (NOS) pathway is involved in the RPEC protection of the rat ischemic kidneys. Material and methods: Male rats were subjected to right nephrectomy and randomized as: (1) sham, no additional intervention; (2) IR, 45 min of renal ischemia followed by 24 h reperfusion; (3) RPEC, four 5 min cycles of lower limb IR administered at the beginning of renal ischemia; (4) RPEC+L-NAME (a non-specific NOS inhibitor, 10 mg/kg, i.p.) (5) RPEC + 1400W (a specific iNOS inhibitor, 1 mg/kg, i.p.).
    [Show full text]
  • Toll-Like Receptor 7 Involves the Injury in Acute Kidney Ischemia/Reperfusion of STZ- Induced Diabetic Rats1
    4 - ORIGINAL ARTICLE ISCHEMIA-REPERFUSION Toll-like receptor 7 involves the injury in acute kidney ischemia/reperfusion of STZ- induced diabetic rats1 Huang YayiI, Xiao YedaII, Wang HuaxinIII, Wu YangIII, Sun QianIII, Xia ZhongyuanIV DOI: http://dx.doi.org/10.1590/S0102-865020160070000004 IMaster, Department of Anesthesia, Renmin Hospital, Wuhan University, China. Conception and design of the study, acquisition and interpretation of data, manuscript writing. IIMaster, Department of Anesthesia, Renmin Hospital, Wuhan University, China. Acquisition of data, critical revision. IIIPhD, Department of Anesthesia, Renmin Hospital, Wuhan University, China. Acquisition of data. IVPhD, Full Professor, Department of Anesthesia, Renmin Hospital, Wuhan University, China. Design and supervised all phases of the study, critical revision. ABSTRACT PURPOSE: To determine whether Toll-like receptor 7 (TLR7) is the potential targets of prevention or progression in the renal ischemia/ reperfusion (I/R) injury of STZ-induced diabetic rats. METHODS: Thirty six Sprague-Dawley rats were randomly arranged to the nondiabetic (ND) or diabetic group (DM), with each group further divided into sham (no I/R injury), I/R (ischemia-reperfusion) and CD (given by Chloroquine) group. Preoperatively, Chloroquine (40 mg/kg, intraperitoneal injection.) was administrated 6 days for treatment group. I/R animals were subjected to 25 min of bilateral renal ischemia. Renal function, histology, apoptosis, cytokines, expression of TLR7, MyD88 and NF-κB were detected. RESULTS: The serum levels of blood urea nitrogen, creatinine, IL-6 and TNF-α, apoptotic tubular epithelial cells, expression of TLR7, MyD88 and NF-κB were significantly increased in DM+I/R group, compared with ND+I/R group (p<0.05).
    [Show full text]
  • Ischemia Reperfusion Injury—A Translational Perspective in Organ Transplantation
    International Journal of Molecular Sciences Review Review: Ischemia Reperfusion Injury—A Translational Perspective in Organ Transplantation André Renaldo Fernández 1, Rodrigo Sánchez-Tarjuelo 2,3, Paolo Cravedi 4 , Jordi Ochando 2,3 and Marcos López-Hoyos 1,5,* 1 Immunology, Universitary Hospital Marqués de Valdecilla- Research Institute IDIVAL Santander, 390008 Santander, Spain; [email protected] 2 Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; [email protected] (R.S.-T.); [email protected] (J.O.) 3 Immunología de Trasplantes, Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28220 Majadahonda (Madrid), Spain 4 Department of Medicine, Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; [email protected] 5 Red de Investigación Renal (REDINREN), 28040 Madrid, Spain * Correspondence: [email protected]; Tel.: +34-942-292759 Received: 30 September 2020; Accepted: 11 November 2020; Published: 13 November 2020 Abstract: Thanks to the development of new, more potent and selective immunosuppressive drugs together with advances in surgical techniques, organ transplantation has emerged from an experimental surgery over fifty years ago to being the treatment of choice for many end-stage organ diseases, with over 139,000 organ transplants performed worldwide in 2019. Inherent to the transplantation procedure is the fact that the donor organ is subjected to blood flow cessation and ischemia during harvesting, which is followed by preservation and reperfusion of the organ once transplanted into the recipient. Consequently, ischemia/reperfusion induces a significant injury to the graft with activation of the immune response in the recipient and deleterious effect on the graft.
    [Show full text]
  • Acute Kidney Injury Leads to Inflammation and Functional Changes in the Brain
    BASIC RESEARCH www.jasn.org Acute Kidney Injury Leads to Inflammation and Functional Changes in the Brain Manchang Liu,* Yideng Liang,† Srinivasulu Chigurupati,‡ Justin D. Lathia,‡ Mikhail Pletnikov,† Zhaoli Sun,§ Michael Crow,* Christopher A. Ross,† Mark P. Mattson,‡ and Hamid Rabb* Departments of *Medicine, †Psychiatry and Behavioral Sciences, and §Surgery, Johns Hopkins University School of Medicine, and ‡Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, Maryland ABSTRACT Although neurologic sequelae of acute kidney injury (AKI) are well described, the pathogenesis of acute uremic encephalopathy is poorly understood. This study examined the short-term effect of ischemic AKI on inflammatory and functional changes of the brain in mice by inducing bilateral renal ischemia for 60 min and studying the brains 24 h later. Compared with sham mice, mice with AKI had increased neuronal pyknosis and microgliosis in the brain. AKI also led to increased levels of the proinflammatory chemo- kines keratinocyte-derived chemoattractant and G-CSF in the cerebral cortex and hippocampus and increased expression of glial fibrillary acidic protein in astrocytes in the cortex and corpus callosum. In addition, extravasation of Evans blue dye into the brain suggested that the blood-brain barrier was disrupted in mice with AKI. Because liver failure also leads to encephalopathy, ischemic liver injury was induced in mice with normal renal function; neuronal pyknosis and glial fibrillary acidic protein expression were not increased, suggesting differential effects on the brain depending on the organ injured. For evaluation of the effects of AKI on brain function, locomotor activity was studied using an open field test.
    [Show full text]
  • Article Acute Respiratory Distress Syndrome and Risk of AKI Among
    Article Acute Respiratory Distress Syndrome and Risk of AKI among Critically Ill Patients Michael Darmon, Christophe Clec’h, Christophe Adrie, Laurent Argaud, Bernard Allaouchiche, Elie Azoulay, Lila Bouadma, Maı¨te´ Garrouste-Orgeas, Hakim Haouache, Carole Schwebel, Dany Goldgran-Toledano, Hatem Khallel, Anne-Sylvie Dumenil, Samir Jamali, Bertrand Souweine, Fabrice Zeni, Yves Cohen, and Jean-Franc¸ois Timsit Abstract Background and objectives Increasing experimental evidence suggests that acute respiratory distress syndrome Due to the number of contributing authors, (ARDS) may promote AKI. The primary objective of this study was to assess ARDS as a risk factor for AKI in the affiliations are critically ill patients. provided in the Supplemental Design, setting, participants, & measurements This was an observational study on a prospective database fed by Material. 18 intensive care units (ICUs). Patients with ICU stays .24 hours were enrolled over a 14-year period. ARDS was defined using the Berlin criteria and AKI was defined using the Risk, Injury, Failure, Loss of kidney function, and Correspondence: Dr. Michael Darmon, End-stage kidney disease criteria. Patients with AKI before ARDS onset were excluded. Medical-Surgical Intensive Care Unit, Results This study enrolled 8029 patients, including 1879 patients with ARDS. AKI occurred in 31.3% of Saint Etienne patients and was more common in patients with ARDS (44.3% versus 27.4% in patients without ARDS; University Hospital, P,0.001). After adjustment for confounders, both mechanical ventilation without ARDS (odds ratio [OR], Avenue Albert fi Raimond, 42270 Saint 4.34; 95% con dence interval [95% CI], 3.71 to 5.10) and ARDS (OR, 11.01; 95% CI, 6.83 to 17.73) were in- Priest in Jarez, France.
    [Show full text]
  • Update and Review of Renal Artery Stenosis
    Disease-a-Month 67 (2021) 101118 Contents lists available at ScienceDirect Disease-a-Month journal homepage: www.elsevier.com/locate/disamonth Update and review of renal artery stenosis ∗ Gates B. Colbert, MD, FASN a, , Graham Abra, MD b,c, Edgar V. Lerma, MD, FACP, FASN, FPSN (Hon) d a Baylor University Medical Center at Dallas, 3417 Gaston Ave, Suite 875, Dallas, TX 75246, USA b Stanford University, Palo Alto, CA, USA c Satellite Healthcare, San Jose, CA, USA d UIC/ Advocate Christ Medical Center, Oak Lawn, IL USA Introduction According to Carey et al., “resistant hypertension (RH) is defined as above-goal elevated blood pressure (BP) in a patient despite the concurrent use of 3 antihypertensive drug classes, com- monly including a long-acting calcium channel blocker, a blocker of the renin-angiotensin sys- tem (RAAS) (angiotensin-converting enzyme inhibitor or angiotensin receptor blocker), and a diuretic”. 1 The causes of RH are: non-adherence with dietary salt restriction, drugs (prescription and non-prescription), obstructive sleep apnea, and secondary hypertension. Secondary hypertension accounts for about 5–10% of all cases of hypertension, whereas pri- mary or essential hypertension accounts for 90%. In a series of 4494 patients referred to hyper- tension specialty clinics, 12.7% had secondary causes overall, of which 35% were associated with occlusive renovascular disease. 2 A more recent series showed that 24% of older subjects (mean age, 71 years) with RH were shown to have significant renal arterial disease, with most cases being caused by atheroscle- rotic disease. 3 However, the syndrome of renovascular hypertension can also result from other less common obstructive lesions (fibromuscular dysplasias, renal artery dissection or infarction, Takayasu arteritis, radiation fibrosis, and renal artery obstruction from aortic endovascular stent grafts).
    [Show full text]
  • Regulated Cell Death in AKI
    BRIEF REVIEW www.jasn.org Regulated Cell Death in AKI † ‡ Andreas Linkermann,* Guochun Chen, Guie Dong, Ulrich Kunzendorf,* Stefan Krautwald,* †‡ and Zheng Dong *Clinic for Nephrology and Hypertension, Christian-Albrechts-University, Kiel, Germany; †Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; and ‡Department of Cellular Biology and Anatomy, Charlie Norwood Veterans Affairs Medical Center and Medical College of Georgia at Georgia Regents University, Augusta, Georgia ABSTRACT AKI is pathologically characterized by sublethal and lethal damage of renal tubules. various forms of cell death are noticeable: Under these conditions, renal tubular cell death may occur by regulated necrosis necrosis and apoptosis. This review sum- (RN) or apoptosis. In the last two decades, tubular apoptosis has been shown in marizes the evidence for the various forms preclinical models and some clinical samples from patients with AKI. Mechanistically, of regulated cell death in AKI, delineates apoptotic cell death in AKI may result from well described extrinsic and intrinsic their underlying mechanisms with an em- pathways as well as ER stress. Central converging nodes of these pathways are phasis on the new insights, and puts forth mitochondria, which become fragmented and sensitized to membrane permeabilization the perspectives of targeting cell death for in response to cellular stress, resulting in the release of cell death–inducing factors. the prevention and therapy of kidney injury. Whereas apoptosis is known to be regulated, tubular necrosis was thought to occur by accident until recent work unveiled several RN subroutines, most prominently receptor- interacting protein kinase–dependent necroptosis and RN induced by mitochondrial APOPTOSIS—THE CLASSIC VIEW permeability transition.
    [Show full text]
  • Carbon Monoxide Protects the Kidney Through the Central Circadian Clock and CD39
    Carbon monoxide protects the kidney through the central circadian clock and CD39 Matheus Correa-Costaa, David Galloa, Eva Csizmadiaa, Edward Gompertsb, Judith-Lisa Lieberuma, Carl J. Hausera,c, Xingyue Jid,e, Binghe Wangd,e, Niels Olsen Saraiva Câmaraf, Simon C. Robsonc, and Leo E. Otterbeina,1 aTransplant Institute, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215; bHillhurst Biopharmaeuticals Inc., Montrose, CA 91020; cTransplant Institute, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215; dDepartment of Chemistry, Georgia State University, Atlanta, GA 30303; eCenter for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303; and fLaboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, 05508-900, Sao Paulo, Brazil Edited by Gregg L. Semenza, Johns Hopkins University School of Medicine, Baltimore, MD, and approved January 24, 2018 (received for review September 22, 2017) Ischemia reperfusion injury (IRI) is the predominant tissue insult tective phenotype that results. Biliverdin and CO are accepted as associated with organ transplantation. Treatment with carbon mon- the primary underlying bioactive molecules that provide potent oxide (CO) modulates the innate immune response associated with IRI protective benefits to the cell by modulating apoptosis, inflam- and accelerates tissue recovery. The mechanism has been primarily mation, and proliferation
    [Show full text]
  • Tumor Necrosis Factor Superfamily Ligand Mrna Expression Profiles
    Devarapu et al. Journal of Biomedical Science (2017) 24:77 DOI 10.1186/s12929-017-0383-3 RESEARCH Open Access Tumor necrosis factor superfamily ligand mRNA expression profiles differ between humans and mice during homeostasis and between various murine kidney injuries Satish Kumar Devarapu1, Julia Felicitas Grill1, Junhui Xie1,2, Marc Weidenbusch1, Mohsen Honarpisheh1, Volker Vielhauer1, Hans-Joachim Anders1 and Shrikant R. Mulay1,3* Abstract Background: Several tumour necrosis factor (TNF) based therapeutics have already been approved for human use and several others are emerging. Therefore, we determined the mRNA expression levels of the TNF superfamily ligands (TNFSF) – e.g. TNF-α, lymphotoxin (LT)-α, LT-β, Fas-L (CD95-L), TNF-related apoptosis-inducing ligand (TRAIL), TNF-related weak inducer of apoptosis (TWEAK), 4-1BBL, OX40-L (CD252) and amyloid precursor protein (APP) in healthy human and mouse solid organs. Methods: We used quantitative real time-PCR to analyse mRNA expression levels of TNFSF ligands. Murine models of acute ischemic renal injury, chronic oxalate nephropathy, and immune complex glomerulonephritis were used. Renal injury was assessed by PAS staining, and infiltrating immune cells were analysed by immunohistochemistry. Data was analysed using non-parametric ANOVA (non-parametric; Kruskal-Wallis test). Results: We observed significant differences in the mRNA expression levels of TNFSF ligands in human and mouse solid organs. Furthermore, we determined their mRNA expressions during acute and chronic kidney injuries in mice. Our data demonstrate that the mRNA expression levels of TNFSF vary depending on the type of tissue injury – for example, acute ischemic renal injury, chronic crystalline nephropathy, and immune complex glomerulonephritis.
    [Show full text]
  • “Point of No Return” in Unilateral Renal Ischemia Reperfusion Injury in Mice
    Holderied et al. Journal of Biomedical Science (2020) 27:34 https://doi.org/10.1186/s12929-020-0623-9 RESEARCH Open Access “Point of no return” in unilateral renal ischemia reperfusion injury in mice Alexander Holderied1* , Franziska Kraft2, Julian Aurelio Marschner2, Marc Weidenbusch2 and Hans-Joachim Anders2 Abstract Background: In the past years evidence has been growing about the interconnection of chronic kidney disease and acute kidney injury. The underlying pathophysiological mechanisms remain unclear. We hypothesized, that a threshold ischemia time in unilateral ischemia/reperfusion injury sets an extent of ischemic tubule necrosis, which as “point of no return” leads to progressive injury. This progress is temporarily associated by increased markers of inflammation and results in fibrosis and atrophy of the ischemic kidney. Methods: Acute tubule necrosis was induced by unilateral ischemia/reperfusion injury in male C57BL/6 N mice with different ischemia times (15, 25, 35, and 45 min). At multiple time points between 15 min and 5 weeks we assessed gene expression of markers for injury, inflammation, and fibrosis, histologically the injury of tubules, cell death (TUNEL), macrophages, neutrophil influx and kidney atrophy. Results: Unilateral ischemia for 15 and 25 min induced upregulation of markers for injury after reperfusion for 24 h but no upregulation after 5 weeks. None of the markers for inflammation or fibrosis were upregulated after ischemia for 15 and 25 min at 24 h or 5 weeks on a gene expression level, except for Il-6. Ischemia for 35 and 45 min consistently induced upregulation of markers for inflammation, injury, and partially of fibrosis (Tgf-β1 and Col1a1) at 24 h and 5 weeks.
    [Show full text]