Transcriptome analysis of renal ischemia/reperfusion (I/R) injury in BAFF and BAFF-R deficient mice

Acute kidney injury (AKI) accompanies with high morbidity and mortality. Incomplete renal recovery can lead to chronic and finally end-stage kidney disease, which results in the requirement of lifelong dialysis or kidney transplantation. Consequently, finding predictive biomarker and therefore developing preventive therapeutic approaches is an urgent need. For this purpose, a better understanding of the mechanism underlying AKI is necessary. The cytokine BAFF (B cell activating factor) is related to AKI by supporting B cells, which in turn play an important role in inflammatory processes and the production of antibodies. In our study, we investigated the role of BAFF and its receptor BAFF-R in the early phase of AKI. Therefore, we performed the well-established ischemia/reperfusion (I/R) model in BAFF (B6.129S2-Tnfsf13btm1Msc/J) and BAFF-R (B6(Cg)-Tnfrsf13ctm1Mass/J) deficient mice. Transcriptome of ischemic and contralateral control kidneys was analyzed and compared to wildtype littermates. We detected the upregulation of Lcn2, Lyz2, Cd44, Fn1 and Il1rn in ischemic kidneys as well as the downregulation of Kl. Furthermore, we revealed different expression patterns in BAFF and BAFF-R knockout mice. Compared to wildtype littermates, up- and downregulation of each investigated gene were higher in BAFF-R knockout and lower in BAFF knockout. Our findings indicate a positive impact of BAFF knockout in early phase of AKI, while BAFF-R knockout seems to worsen I/R injury. In addition, our study shows for the first time a remarkable renal upregulation of Lyz2 in a murine I/R model. Therefore, we consider Lyz2 as conceivable predictive or early biomarker in case of I/R and AKI.

[1]  L. Lv,et al.  KIM-1 augments hypoxia-induced tubulointerstitial inflammation through uptake of small extracellular vesicles by tubular epithelial cells , 2022, Molecular therapy : the journal of the American Society of Gene Therapy.

[2]  Hui-Hua Li,et al.  Blockage of Fibronectin 1 Ameliorates Myocardial Ischemia/Reperfusion Injury in Association with Activation of AMP-LKB1-AMPK Signaling Pathway , 2022, Oxidative medicine and cellular longevity.

[3]  Jiang Liu,et al.  Clinical pharmacology considerations for the approval of belimumab for the treatment of adult patients with active lupus nephritis: A regulatory perspective , 2022, Lupus.

[4]  M. Khamashta,et al.  10 Years of belimumab experience: What have we learnt? , 2021, Lupus.

[5]  A. Amirzargar,et al.  Investigating the Role of BAFF and Its Receptors in Renal Transplant Recipients with Chronic Antibody-Mediated Rejection , 2021, Journal of immunology research.

[6]  H. Kitamura,et al.  A rare cause of acute kidney injury with chronic myelomonocytic leukemia , 2021, CEN Case Reports.

[7]  A. Schwarting,et al.  B cell activating factor (BAFF): Structure, functions, autoimmunity and clinical implications in Systemic Lupus Erythematosus (SLE). , 2020, Autoimmunity reviews.

[8]  N. Rioux-Leclercq,et al.  [Lysozyme-induced nephropathy: A rare cause of renal failure in chronic myelomonocytic leukemia]. , 2020, Annales de pathologie.

[9]  A. Vlahou,et al.  Multiplexed MRM-based protein quantification of putative prognostic biomarkers for chronic kidney disease progression in plasma , 2020, Scientific Reports.

[10]  H. Anders,et al.  “Point of no return” in unilateral renal ischemia reperfusion injury in mice , 2020, Journal of Biomedical Science.

[11]  B. Banas,et al.  Anti-BAFF Treatment Interferes With Humoral Responses in a Model of Renal Transplantation in Rats , 2020, Transplantation.

[12]  R. Irizarry.  ggplot2 , 2019, Introduction to Data Science.

[13]  J. Raemaekers,et al.  Progressive kidney failure in chronic myelomonocytic leukaemia: don't forget lysozyme damage. , 2018, The Netherlands journal of medicine.

[14]  A. Amirzargar,et al.  Interferon regulatory factors: Where to stand in transplantation. , 2018, Transplant immunology.

[15]  Haiyan Xu,et al.  B Cell Activating Factor, Renal Allograft Antibody-Mediated Rejection, and Long-Term Outcome , 2018, Journal of immunology research.

[16]  Xuliang Jiang,et al.  A loop region of BAFF controls B cell survival and regulates recognition by different inhibitors , 2018, Nature Communications.

[17]  Z. Ni,et al.  Klotho Reduces Necroptosis by Targeting Oxidative Stress Involved in Renal Ischemic-Reperfusion Injury , 2018, Cellular Physiology and Biochemistry.

[18]  J. Hillebrands,et al.  Tissue expression and source of circulating αKlotho. , 2017, Bone.

[19]  Hadley Wickham,et al.  ggplot2 - Elegant Graphics for Data Analysis (2nd Edition) , 2017 .

[20]  F. Claas,et al.  B Cell Immunity in Solid Organ Transplantation , 2017, Front. Immunol..

[21]  G. Kocic,et al.  Molecular Dissection of Renal Ischemia-Reperfusion: Oxidative Stress and Cellular Events. , 2016, Current medicinal chemistry.

[22]  H. Ni,et al.  Fibronectin maintains the balance between hemostasis and thrombosis , 2016, Cellular and Molecular Life Sciences.

[23]  H. Ni,et al.  Fibronectin maintains the balance between hemostasis and thrombosis , 2016, Cellular and Molecular Life Sciences.

[24]  Lior Pachter,et al.  Near-optimal probabilistic RNA-seq quantification , 2016, Nature Biotechnology.

[25]  Geetha Chalasani,et al.  B Cells, Antibodies, and More. , 2015, Clinical journal of the American Society of Nephrology : CJASN.

[26]  L. Hsiao,et al.  KIM-1-mediated phagocytosis reduces acute injury to the kidney. , 2015, The Journal of clinical investigation.

[27]  W. Huber,et al.  Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2 , 2014, Genome Biology.

[28]  P. D. De Jager,et al.  Blood kidney injury molecule-1 is a biomarker of acute and chronic kidney injury and predicts progression to ESRD in type I diabetes. , 2014, Journal of the American Society of Nephrology : JASN.

[29]  Z. Ni,et al.  Diagnostic Value of Urinary Kidney Injury Molecule 1 for Acute Kidney Injury: A Meta-Analysis , 2014, PloS one.

[30]  Benjamin A. Neely,et al.  Evaluation of 32 urine biomarkers to predict the progression of acute kidney injury after cardiac surgery , 2013, Kidney international.

[31]  A. McMahon,et al.  Chronic epithelial kidney injury molecule-1 expression causes murine kidney fibrosis. , 2013, The Journal of clinical investigation.

[32]  M. Clatworthy,et al.  Elevated Pretransplantation Soluble BAFF Is Associated With an Increased Risk of Acute Antibody-Mediated Rejection , 2013, Transplantation.

[33]  K. Fairfax,et al.  The BAFF/APRIL system: Emerging functions beyond B cell biology and autoimmunity , 2013, Cytokine & Growth Factor Reviews.

[34]  B. Hahn.  Belimumab for systemic lupus erythematosus. , 2013, The New England journal of medicine.

[35]  Hermann Brenner,et al.  Kidney Graft Survival in Europe and the United States: Strikingly Different Long-Term Outcomes , 2013, Transplantation.

[36]  S. Brouard,et al.  BAFF and BAFF‐R Levels Are Associated With Risk of Long‐Term Kidney Graft Dysfunction and Development of Donor‐Specific Antibodies , 2012, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[37]  Y. Nabeshima,et al.  Decreased renal α-Klotho expression in early diabetic nephropathy in humans and mice and its possible role in urinary calcium excretion. , 2012, Kidney international.

[38]  A. Matas,et al.  Understanding the Causes of Kidney Transplant Failure: The Dominant Role of Antibody‐Mediated Rejection and Nonadherence , 2012, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[39]  Celeste B. Burness,et al.  Belimumab , 2011, Drugs.

[40]  M. Kuro-o,et al.  Klotho deficiency is an early biomarker of renal ischemia-reperfusion injury and its replacement is protective. , 2010, Kidney international.

[41]  J. Thurman,et al.  B Cell Subsets Contribute to Renal Injury and Renal Protection after Ischemia/Reperfusion , 2010, The Journal of Immunology.

[42]  M. Ohnishi,et al.  Dietary and genetic evidence for phosphate toxicity accelerating mammalian aging , 2010, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[43]  H. Rabb,et al.  B cells limit repair after ischemic acute kidney injury. , 2010, Journal of the American Society of Nephrology : JASN.

[44]  D. DeAngelo,et al.  A forgotten cause of kidney injury in chronic myelomonocytic leukemia. , 2009, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[45]  X. He,et al.  Abnormal high expression of B-cell activating factor belonging to the TNF superfamily (BAFF) associated with long-term outcome in kidney transplant recipients. , 2009, Transplantation proceedings.

[46]  H. Lee,et al.  Urinary biomarkers in the early detection of acute kidney injury after cardiac surgery. , 2009, Clinical journal of the American Society of Nephrology : CJASN.

[47]  J. Michel,et al.  B Cell Survival in Intragraft Tertiary Lymphoid Organs After Rituximab Therapy , 2008, Transplantation.

[48]  Hai Huang,et al.  Administration of interleukin‐1 receptor antagonist ameliorates renal ischemia‐reperfusion injury , 2008, Transplant international : official journal of the European Society for Organ Transplantation.

[49]  M. C. V. D. Heuvel,et al.  Tubular kidney injury molecule‐1 (KIM‐1) in human renal disease , 2007, The Journal of pathology.

[50]  K. Okawa,et al.  Klotho converts canonical FGF receptor into a specific receptor for FGF23 , 2006, Nature.

[51]  R. Rezzani,et al.  Role of Carbon Monoxide and Biliverdin in Renal Ischemia/Reperfusion Injury , 2006, Nephron Experimental Nephrology.

[52]  K. Rosenblatt,et al.  Regulation of Fibroblast Growth Factor-23 Signaling by Klotho* , 2006, Journal of Biological Chemistry.

[53]  Joseph V Bonventre,et al.  Urinary kidney injury molecule-1: a sensitive quantitative biomarker for early detection of kidney tubular injury. , 2006, American journal of physiology. Renal physiology.

[54]  N. Rothwell,et al.  Interleukin-1 and neuronal injury , 2005, Nature Reviews Immunology.

[55]  K. Rouschop,et al.  Protection against renal ischemia reperfusion injury by CD44 disruption. , 2005, Journal of the American Society of Nephrology : JASN.

[56]  M. Scott,et al.  BAFF binding to T cell‐expressed BAFF‐R costimulates T cell proliferation and alloresponses , 2004, European journal of immunology.

[57]  J. Kutok,et al.  TNF Family Member B Cell-Activating Factor (BAFF) Receptor-Dependent and -Independent Roles for BAFF in B Cell Physiology1 , 2004, The Journal of Immunology.

[58]  Sambasiva P Rao,et al.  B Cell-Activating Factor Belonging to the TNF Family Acts through Separate Receptors to Support B Cell Survival and T Cell-Independent Antibody Formation , 2004, The Journal of Immunology.

[59]  C. Mackay,et al.  B Cell-Activating Factor Belonging to the TNF Family (BAFF)-R Is the Principal BAFF Receptor Facilitating BAFF Costimulation of Circulating T and B Cells1 , 2004, The Journal of Immunology.

[60]  R. Bram,et al.  BCMA Is Essential for the Survival of Long-lived Bone Marrow Plasma Cells , 2004, The Journal of experimental medicine.

[61]  P. Devarajan,et al.  Gene expression in early ischemic renal injury: clues towards pathogenesis, biomarker discovery, and novel therapeutics. , 2003, Molecular genetics and metabolism.

[62]  M. Mitsnefes,et al.  Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. , 2003, Journal of the American Society of Nephrology : JASN.

[63]  K. Rouschop,et al.  Reciprocal functions of hepatocyte growth factor and transforming growth factor-beta1 in the progression of renal diseases: a role for CD44? , 2003, Kidney international. Supplement.

[64]  W. Baldwin,et al.  B Cell Deficiency Confers Protection from Renal Ischemia Reperfusion Injury 1 , 2003, The Journal of Immunology.

[65]  M. Scott,et al.  Normal B Cell Homeostasis Requires B Cell Activation Factor Production by Radiation-resistant Cells , 2003, The Journal of experimental medicine.

[66]  S. Tangye,et al.  BAFF selectively enhances the survival of plasmablasts generated from human memory B cells. , 2003, The Journal of clinical investigation.

[67]  R. Kucherlapati,et al.  Differential gene expression following early renal ischemia/reperfusion. , 2003, Kidney international.

[68]  B. Padanilam.  Cell death induced by acute renal injury: a perspective on the contributions of apoptosis and necrosis. , 2003, American journal of physiology. Renal physiology.

[69]  P. Valdez,et al.  Loss of TACI causes fatal lymphoproliferation and autoimmunity, establishing TACI as an inhibitory BLyS receptor. , 2003, Immunity.

[70]  H. Erdjument-Bromage,et al.  An iron delivery pathway mediated by a lipocalin. , 2002, Molecular cell.

[71]  J. Bonventre,et al.  Kidney Injury Molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury. , 2002, Kidney international.

[72]  V. Dixit,et al.  Identification of a novel receptor for B lymphocyte stimulator that is mutated in a mouse strain with severe B cell deficiency , 2001, Current Biology.

[73]  J. Tschopp,et al.  BAFF-R, a Newly Identified TNF Receptor That Specifically Interacts with BAFF , 2001, Science.

[74]  M. Scott,et al.  An Essential Role for BAFF in the Normal Development of B Cells Through a BCMA-Independent Pathway , 2001, Science.

[75]  V. Dixit,et al.  Activation and accumulation of B cells in TACI-deficient mice , 2001, Nature Immunology.

[76]  J. V. van Deursen,et al.  Regulation of the T-independent humoral response by TACI. , 2001, Immunity.

[77]  Amy S Orr,et al.  BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator. , 1999, Science.

[78]  J. Tschopp,et al.  BAFF, a Novel Ligand of the Tumor Necrosis Factor Family, Stimulates B Cell Growth , 1999, The Journal of experimental medicine.

[79]  D. Jeyarajah,et al.  Hypothesis: is renal allograft rejection initiated by the response to injury sustained during the transplant process? , 1999, Kidney international.

[80]  Joseph V. Bonventre,et al.  Kidney Injury Molecule-1 (KIM-1), a Putative Epithelial Cell Adhesion Molecule Containing a Novel Immunoglobulin Domain, Is Up-regulated in Renal Cells after Injury* , 1998, The Journal of Biological Chemistry.

[81]  Borland,et al.  Forms and functions of CD44 , 1998, Immunology.

[82]  R. Wüthrich,et al.  Upregulated renal tubular CD44, hyaluronan, and osteopontin in kdkd mice with interstitial nephritis. , 1997, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[83]  J. H. van Bockel,et al.  Risk factors for delayed graft function in cadaveric kidney transplantation: a prospective study of renal function and graft survival after preservation with University of Wisconsin solution in multi-organ donors. European Multicenter Study Group. , 1997, Transplantation.

[84]  B. Molitoris,et al.  Acute renal failure in the 21st century: recommendations for management and outcomes assessment. , 1997, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[85]  R. Schrier,et al.  The nature of renal cell injury. , 1997, Kidney international.

[86]  J. Williams,et al.  CD44 in glomerulonephritis: expression in human renal biopsies, the Thy 1.1 model, and by cultured mesangial cells. , 1996, Kidney international.

[87]  R. Wüthrich,et al.  Enhanced tubular epithelial CD44 expression in MRL-lpr lupus nephritis. , 1996, Kidney international.

[88]  C. Isacke,et al.  A Di-hydrophobic Leu-Val Motif Regulates the Basolateral Localization of CD44 in Polarized Madin-Darby Canine Kidney Epithelial Cells (*) , 1996, The Journal of Biological Chemistry.

[89]  M. Nicholson,et al.  Renal ischaemia‐reperfusion injury , 1996, The British journal of surgery.

[90]  M. Paller.  The cell biology of reperfusion injury in the kidney. , 1994, Journal of investigative medicine : the official publication of the American Federation for Clinical Research.

[91]  S. Neame,et al.  The cytoplasmic tail of CD44 is required for basolateral localization in epithelial MDCK cells but does not mediate association with the detergent-insoluble cytoskeleton of fibroblasts , 1993, The Journal of cell biology.

[92]  B. Molitoris.  The potential role of ischemia in renal disease progression. , 1992, Kidney international. Supplement.

[93]  D. Dripps,et al.  Interleukin-1 (IL-1) receptor antagonist binds to the 80-kDa IL-1 receptor but does not initiate IL-1 signal transduction. , 1991, The Journal of biological chemistry.

[94]  P. Coratelli,et al.  Comparison of urinary enzyme pattern in renal transplant recipients receiving two different immunosuppressive regimens: azathioprine versus ciclosporin. , 1988, Contributions to nephrology.

[95]  K. Baumann,et al.  Early nephrotoxicity at high plasma concentrations of lysozyme in the rat. , 1982, Laboratory investigation; a journal of technical methods and pathology.

[96]  Y. Collan,et al.  Immunohistochemical identification of renal lysozyme during allograft rejection in man , 1979, Histopathology.

[97]  M. Venkatachalam,et al.  Ischemic damage and repair in the rat proximal tubule: differences among the S1, S2, and S3 segments. , 1978, Kidney international.

[98]  R. R. Mcswiney,et al.  Urinary Excretion of Lysozyme and N-Acetyl-β-D-Glucosaminidase in the Diagnosis of Renal Allograft Rejection , 1978, Annals of clinical biochemistry.

[99]  J. Zazgornik,et al.  [Behaviour of serum and urinary lysozyme after renal transplantation (author's transl)]. , 1977, Wiener klinische Wochenschrift.

[100]  T. Niwa,et al.  Serum and urinary lysozyme activities in patients with renal diseases. , 1974, The Tohoku journal of experimental medicine.

[101]  I. Shehadeh,et al.  Renal allograft rejection. An analysis of lysozymuria, serum complement, lymphocyturia, and heterophil antibodies. , 1970 .

[102]  A. S. Appel,et al.  ACUTE RENAL FAILURE , 1967, Advances in Experimental Medicine and Biology.

[103]  R. Noble,et al.  Urine and serum lysozyme alterations in a case of acute renal failure. , 1966, The Journal of urology.

[104]  D. Prockop,et al.  A STUDY OF URINARY AND SERUM LYSOZYME IN PATIENTS WITH RENAL DISEASE. , 1964, The New England journal of medicine.

[105]  Aruthur E. Guedel,et al.  Inhalation anesthesia : a fundamental guide , 1937 .

[106]  J. Sellarésa,et al.  Understanding the Causes of Kidney Transplant Failure : The Dominant Role of Antibody-Mediated Rejection and Nonadherence , 2011 .

[107]  X. He,et al.  The expression of B-cell activating factor belonging to tumor necrosis factor superfamily (BAFF) significantly correlated with C4D in kidney allograft rejection. , 2009, Transplantation proceedings.

[108]  B. Jaber,et al.  Urinary N-acetyl-beta-(D)-glucosaminidase activity and kidney injury molecule-1 level are associated with adverse outcomes in acute renal failure. , 2007, Journal of the American Society of Nephrology : JASN.

[109]  P. Moore,et al.  Synthesis and release of B-lymphocyte stimulator from myeloid cells. , 2001, Blood.

[110]  B. Padanilam,et al.  Expression of CD44 in kidney after acute ischemic injury in rats. , 2000, American journal of physiology. Regulatory, integrative and comparative physiology.

[111]  V. Garcia-Nieto,et al.  Acute renal failure. , 1996, The New England journal of medicine.

[112]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[113]  D. Cosman.  A family of ligands for the TNF receptor superfamily , 1994, Stem cells.

[114]  L. Matturri,et al.  Renal allograft rejection: immunohistochemistry of inflammatory cellular subsets and vascular lesions. , 1986, Basic and applied histochemistry.

[115]  E. Lewis,et al.  Serum and urine beta-2-microglobulin and lysozyme concentrations in transplant rejection. , 1979, Proceedings of the Clinical Dialysis and Transplant Forum.

[116]  G. Horpácsy,et al.  Continuous determination of various enzymes and sodium concentration in urine. a usable method for diagnosis of kidney graft rejection. , 1978, European urology.