Matthew D Griffin

St. Ann's University Hospital Brno, Brünn, South Moravian, Czech Republic

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Publications (119)653.75 Total impact

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    ABSTRACT: Mesenchymal stem cells (MSCs) suppress T-helper (Th)-17 cell differentiation and are being pursued clinically for the treatment of conditions associated with aberrant Th17 responses. Whether such immunomodulatory effects are enhanced by co-administration of MSCs with other agents is not well known. In this study, the individual and combined effects of MSCs and the vitamin D receptor (VDR) agonist paricalcitol on Th17 induction were investigated in vitro and in a mouse model of sterile kidney inflammation (unilateral ureteral obstruction). In-vitro, MSCs and paricalcitol additively suppressed Th17 differentiation although only MSCs suppressed expression of Th17-associated transcriptions factors. The combined administration of MSCs and paricalcitol resulted in early (day 3) reduction of intra-renal CD4(+) and CD8(+) T-cells, CD11b(+)/Ly6G(+) neutrophils and inflammatory (Ly6C(hi)) monocytes as well as reduced transcript for IL-17. Later (day 8), obstructed kidneys of MSC and paricalcitol double-treated, but not single-treated, mice had reduced tubular injury and interstitial fibrosis as well as lower numbers of neutrophils and inflammatory monocytes and an increase in the ratio between M2 (CD206(+)) and M1 (CD206(-)) macrophages compared to controls. Adjunctive therapy with VDR agonists may represent a strategy for enhancing the immunosuppressive properties of MSCs in the setting of pathogenic Th17-type immune responses and related inflammatory responses.
    American journal of physiology. Renal physiology 10/2014; · 3.61 Impact Factor
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    ABSTRACT: Mesenchymal stem cells (MSCs) are an adult stromal cell population possessing potent differentiation capacity and a potential for use across major histocompatibility complex barriers. Although allogeneic MSCs have potent immunosuppressive properties, evidence also suggests that they elicit a weak allogeneic immune response. However, the effect of induced differentiation on the immunosuppressive ability and immunogenicity of allogeneic MSCs is a potential obstacle when applying MSCs in tissue replacement therapies. These concerns will be explored in this review, with particular emphasis on changes in the cell surface expression of immunogenic markers, changes in the secretion of immunosuppressive molecules and in vivo functional benefits of the cell therapy. We review the literature from a translational point of view, focusing on pre-clinical studies that have utilised and analysed the effects of allogeneic immune responses on the ability of allogeneic MSCs to regenerate damaged tissue in models of bone, heart and cartilage defects
    Stem Cell Research & Therapy 08/2014; 5(99). · 3.65 Impact Factor
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    ABSTRACT: Mesenchymal stem cells (MSCs) are being investigated extensively due to their ability to dampen immune responses. Here, we tested the ability of MSCs from three distinct sources to prolong rat corneal allograft survival. A fully allogeneic rat cornea transplant model (DA to LEW) was used. Recipient rats received 1 × 106 MSCs (syn [LEW], allo [DA] or third-party [Wistar Furth]) intravenously 7 days before transplantation and again on the day of transplantation (day 0). A high percentage of untreated and syn-MSC treated allografts were rejected (80% and 100%, respectively). Preactivation of syn-MSCs with interferon gamma also failed to prolong allograft survival. Conversely, corneal allograft survival was significantly prolonged in allo-MSC treated (90%) and third-party MSC treated (80%) allograft recipients. Flow cytometric analysis revealed less infiltrating natural killer T cells in corneas of both allo- and third-party MSC treated animals, coupled with a higher proportion of splenic CD4+Foxp3+ regulatory T cells, compared to controls. In the case of allo- and third-party MSCs, results from a delayed-type hypersensitivity assay clearly showed that hypo-responsiveness was specific for corneal donor-associated allo-antigens. Thus, allo- and third-party MSC treatment prolongs corneal allograft survival by suppressing peripheral immune responses and promoting an intragraft immunoregulatory milieu.
    American Journal of Transplantation 08/2014; · 6.19 Impact Factor
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    ABSTRACT: Multipotent mesenchymal stromal cells are multipotent cells capable of differentiating into different mesodermal cell types. Enigmatically, mesenchymal stromal cells present in the bone marrow support early lymphopoiesis yet can inhibit mature lymphocyte growth. Critical features of the bone marrow microenvironment, such as the level of oxygen, play an important role in mesenchymal stromal cell biology. Herein, we show that a panel of continuously growing mouse mesenchymal stromal cell lines, namely OP9, MS5, PA6, ST2 and B16-14, exhibit mesenchymal stromal cell characteristic phenotypes and respond physiologically to oxygen deprivation. Culturing freshly isolated bone marrow-derived mesenchymal stromal cells or cell lines at 5% O2 resulted in a dramatic increase in expression of hypoxia-inducible factor family members and of key genes involved in their differentiation. Phenotypically, their osteogenic and adipogenic differentiation capacity was generally improved in hypoxia, whereas their inhibitory effects on in vitro T-cell proliferation were preserved. Taken together, we conclude that these continuously growing mouse cell lines behave as canonical mesenchymal stromal cells and respond physiologically to hypoxia, thereby providing a potent tool for the study of different aspects of mesenchymal stromal cell biology.Immunology and Cell Biology advance online publication, 29 April 2014; doi:10.1038/icb.2014.30.
    Immunology and Cell Biology 04/2014; · 3.93 Impact Factor
  • Senthilkumar Alagesan, Matthew D Griffin
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    ABSTRACT: Infusing ex vivo-generated alternatively activated macrophages (AAM) has shown promise in experimental systems as a therapeutic strategy for inflammatory kidney disease. In the mouse Adriamycin nephropathy model, however, Cao et al. report that AAM derived from bone marrow precursors fail to ameliorate disease severity. Absence of the anticipated protective effect resulted from a loss of macrophage anti-inflammatory (M2) phenotype following trafficking to injured kidney-an effect that was mediated by localized colony-stimulating factor-1-dependent macrophage proliferation.
    Kidney International 04/2014; 85(4):730-3. · 8.52 Impact Factor
  • Hatem Amer, Matthew D Griffin
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    ABSTRACT: In follow-up to a recently published randomized controlled clinical trial, Issa et al. provide evidence that systemic activity and physiological responsiveness of the renin aldosterone angiotensin system (RAAS) are well within normal limits in most kidney recipients during the first 5 years post-transplant. Implications of the results include the need to better understand intra-renal RAAS activity in transplanted kidneys and to identify patients in which the graft-protective effects of RAAS blockade are most relevant.
    Kidney International 02/2014; 85(2):240-3. · 8.52 Impact Factor
  • Senthilkumar Alagesan, Matthew D Griffin
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    ABSTRACT: Recent developments toward the successful clinical application of autologous and allogeneic mesenchymal stem cells (MSCs) to organ transplantation are summarized with a focus on safety and efficacy. Clinical trials in organ transplantation and other conditions indicate that infusion of autologous or allogeneic MSCs is generally well tolerated. However, new studies also suggest that efficacy may be curtailed by sequestration in the lungs and early elimination. Safety concerns regarding autologous and/or allogeneic MSCs that have recently been investigated include transient proinflammatory effects, influences on opportunistic infections and cancers and alloantibody induction. Animal models indicate that autologous MSCs are likely to be efficacious in preventing or treating early intragraft inflammation and may reduce the risk of acute rejection - observations that have been borne out in a randomized controlled trial of living-donor kidney transplantation. The potential for donor-specific or third-party allogeneic MSCs to promote allograft tolerance is suggested by animal model studies but has not yet been proven in humans. Recent reports on the safety and efficacy of autologous MSCs for early posttransplant outcomes give cause for optimism. Benefits of allogeneic MSCs for long-term allograft survival and of MSCs for chronic transplant injury await clinical validation.
    Current opinion in organ transplantation 12/2013; · 3.27 Impact Factor
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    ABSTRACT: Allogeneic mesenchymal stem cells (MSC) have potent regenerative and immunosuppressive potential and are being investigated as a therapy for osteoarthritis, however little is known about the immunological changes that occur in allogeneic MSC after ex vivo induced or in vivo differentiation. 3D chondrogenic differentiation was induced in an alginate matrix, which served to immobilize and potentially protect MSC at the site of implantation. We show that allogeneic differentiated MSC lost the ability to inhibit T-cell proliferation in vitro, in association with reduced nitric oxide & prostaglandin E2 secretion. Differentiation altered immunogenicity as evidenced by induced proliferation of allogeneic T cells, and increased susceptibility to cytotoxic lysis by allo-specific T cells. Undifferentiated or differentiated allogeneic MSC were implanted subcutaneously, with and without alginate encapsulation. Increased CD3(+) and CD68(+) infiltration was evident in differentiated and splenocyte encapsulated implants only. Without encapsulation, increased local memory T-cell responses were detectable in recipients of undifferentiated and differentiated MSC; however only differentiated MSC induced systemic memory T-cell responses. In recipients of encapsulated allogeneic cells, only differentiated allogeneic MSC induced memory T-cell responses locally and systemically. Systemic allo-immune responses to differentiated MSC indicate immunogenicity regardless of alginate encapsulation and may require immunosuppressive therapy for therapeutic use.Molecular Therapy (2013); doi:10.1038/mt.2013.261.
    Molecular Therapy 11/2013; · 7.04 Impact Factor
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    ABSTRACT: Mesenchymal stromal (stem) cells (MSCs) continue to be a strong area of focus for academic- and industry-based researchers who share the goal of expanding their therapeutic use for diverse inflammatory and immune-mediated diseases. Recently, there has been an accelerated rate of scientific publication, clinical trial activity and commercialisation in the field. This has included the reporting of exciting new developments in four areas that will be of key importance to future successful use of MSC-based therapies in large numbers of patients: (a) Fundamental biology of the primary cells in bone marrow and other tissues that give rise to MSCs in culture. (b) Mechanisms by which MSCs modulate immune and inflammatory responses in vivo. (c) Insights into MSC kinetics, safety and efficacy in relevant animal disease models. (d) Isolation, definition and clinical trial-based testing of human MSCs by biomedical companies and academic medical centres. Despite this progress, it remains unclear whether MSCs will enter mainstream therapeutic practice as a frequently-used alternative to pharmacotherapy or surgical/radiological procedures in the foreseeable future. In this review we summarise some of the most significant new developments for each of the four areas that contribute to the process of translating MSC research to the clinical arena. In the context of this recent progress, we discuss key challenges and specific knowledge gaps which, if not addressed in a coordinated fashion, may hinder the creation of robust "translational pipelines" for consolidating the status of MSC-based therapies.
    Stem Cells 06/2013; · 7.70 Impact Factor
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    ABSTRACT: Postkidney transplant hyperparathyroidism is a significant problem. Vitamin D receptor agonists are known to suppress parathyroid hormone (PTH) secretion. We examined the effect of oral paricalcitol on posttransplant secondary hyperparathyroidism by conducting an open label randomized trial in which 100 incident kidney transplant recipients were randomized 1:1 to receive oral paricalcitol, 2 μg per day, for the first year posttransplant or no additional therapy. Serial measurements of serum PTH, calcium and bone alkaline phosphatase, 24-h urine calcium and bone density were performed. The primary endpoint was the frequency of hyperparathyroidism 1-year posttransplant. Eighty-seven patients completed the trial. One-year posttransplant, 29% of paricalcitol-treated subjects had hyperparathyroidism compared with 63% of untreated patients (p = 0.0005). Calcium supplementation was discontinued in two control and 15 treatment patients due to mild hypercalcemia or hypercalcuria. Paricalcitol was discontinued in four patients due to hypercalcuria/hypercalcemia and in one for preference. Two subjects required decreasing the dose of paricalcitol to 1 μg daily. Hypercalcemia was asymptomatic and reversible. Incidence of acute rejection, BK nephropathy and renal function at 1 year were similar between groups. Moderate renal allograft fibrosis was reduced in treated patients. Oral paricalcitol is effective in decreasing posttransplant hyperparathyroidism and may have beneficial effects on renal allograft histology.
    American Journal of Transplantation 04/2013; · 6.19 Impact Factor
  • Jana Pindjakova, Matthew D Griffin
    Journal of the American Society of Nephrology 03/2013; · 8.99 Impact Factor
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    ABSTRACT: Urinary extracellular vesicles (uEVs) are released by cells throughout the nephron and contain biomolecules from their cells of origin. Although uEV-associated proteins and RNA have been studied in detail, little information exists regarding uEV glycosylation characteristics. Surface glycosylation profiling by flow cytometry and lectin microarray was applied to uEVs enriched from urine of healthy adults by ultracentrifugation and centrifugal filtration. The carbohydrate specificity of lectin microarray profiles was confirmed by competitive sugar inhibition and carbohydrate-specific enzyme hydrolysis. Glycosylation profiles of uEVs and purified Tamm Horsfall protein were compared. In both flow cytometry and lectin microarray assays, uEVs demonstrated surface binding, at low to moderate intensities, of a broad range of lectins whether prepared by ultracentrifugation or centrifugal filtration. In general, ultracentrifugation-prepared uEVs demonstrated higher lectin binding intensities than centrifugal filtration-prepared uEVs consistent with lesser amounts of co-purified non-vesicular proteins. The surface glycosylation profiles of uEVs showed little inter-individual variation and were distinct from those of Tamm Horsfall protein, which bound a limited number of lectins. In a pilot study, lectin microarray was used to compare uEVs from individuals with autosomal dominant polycystic kidney disease to those of age-matched controls. The lectin microarray profiles of polycystic kidney disease and healthy uEVs showed differences in binding intensity of 6/43 lectins. Our results reveal a complex surface glycosylation profile of uEVs that is accessible to lectin-based analysis following multiple uEV enrichment techniques, is distinct from co-purified Tamm Horsfall protein and may demonstrate disease-specific modifications.
    PLoS ONE 01/2013; 8(9):e74801. · 3.53 Impact Factor
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    ABSTRACT: Mesenchymal stem (stromal) cells (MSCs) have potent anti-inflammatory/immunosuppressive properties which underlie much of their therapeutic potential. This fact has led to the widely accepted belief that MSCs from genetically unrelated individuals (allogeneic (allo)-MSCs) can be used therapeutically with equal efficacy to autologous MSCs and without triggering the donor-specific immune responses that are typically associated with allo-transplants. In this article, we critically review available experimental data to determine whether good in vivo evidence exists in support of the 'immune privileged' status of allo-MSCs. We also examine published studies regarding the immunogenicity of allo-MSCs following activation ('licensing') by inflammatory stimuli or following differentiation. Among the identified studies which have addressed in vivo immunogenicity of allo-MSCs, there was substantial variability as regards experimental species, disease model, route of MSC administration, cell dose and stringency of the immunological assays employed. Nonetheless, the majority of these studies has documented specific cellular (T-cell) and humoral (B-cell/antibody) immune responses against donor antigens following administration of non-manipulated, interferon-γ-activated and differentiated allo-MSCs. The consequences of such anti-donor immune responses were also variable and ranged from reduced in vivo survival of allo-MSCs with accelerated rejection of subsequent allogeneic transplants to apparent promotion of donor-specific tolerance. On the basis of these findings and on existing knowledge of allo-antigen recognition from the field of transplant immunology, we propose that the concept of the immune privileged nature of allo-MSCs should be reconsidered and that the range and clinical implications of anti-donor immune responses elicited by allo-MSCs be more precisely studied in human and animal recipients.Immunology and Cell Biology advance online publication, 4 December 2012; doi:10.1038/icb.2012.67.
    Immunology and Cell Biology 12/2012; · 3.93 Impact Factor
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    ABSTRACT: Conjugated linoleic acid (CLA) induces regression of preestablished atherosclerosis in the ApoE(-/-) mouse. Understanding the mechanisms involved may help in identifying novel pathways associated with the regression of human disease. Animals were administered a 1% cholesterol diet for 12 wk, with 1% CLA supplementation from wk 8 to 12. ApoE(-/-) mice fed only the 1% cholesterol diet for 12 wk were employed as controls. Transcriptomic analysis of mouse aorta showed that many of the components of the IL-10 signaling pathway were modified during CLA-induced regression. Real-time PCR and Western blot analysis showed increased IL-10 receptor expression, phosphorylation of STAT3, and downstream target gene expression in the aorta, alongside an increase in serum IL-10 (79.8±22.4 vs. 41.9±5.5 pg/ml, n=10; P<0.01). CLA -supplementation also increased IL-10 production in bone marrow-derived macrophages (143.6±28.6 vs. 94±5.6 pg/ml, n=5; P<0.05). To explore the mechanisms for altered IL-10 production, we examined the profile of monocyte/macrophage phenotype in the vessel wall, bone marrow, and spleen. CLA increased macrophage polarization toward an anti-inflammatory M2 phenotype in vivo, increasing the population of Ly6C(lo) monocytes (29 vs. 77±14, n=5, P < 0.05) in the aorta. CLA had similar effects on monocytes/macrophages differentiated from marrow-derived progenitor cells and on splenocytes. The induction of IL-10 on CLA supplementation in this model may reflect a systemic alteration toward an anti-inflammatory phenotype, which, in turn promotes increased vascular infiltration by Ly6C(lo) monocytes. These cells may contribute to CLA-induced disease regression.-McCarthy, C., Duffy, M. M., Mooney, D., James, W. G., Griffin, M. D., Fitzgerald, D. J., Belton, O. IL-10 mediates the immunoregulatory response in conjugated linoleic acid-induced regression of atherosclerosis.
    The FASEB Journal 10/2012; · 5.70 Impact Factor
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    ABSTRACT: BACKGROUND: After the first year after kidney transplantation, 3% to 5% of grafts fail each year but detailed studies of how grafts progress to failure are lacking. This study aimed to analyze the functional stability of kidney transplants between 1 and 5 years after transplantation and to identify initially well-functioning grafts with progressive decline in allograft function. METHODS: The study included 788 adult conventional kidney transplants performed at the Mayo Clinic Rochester between January 2000 and December 2005 with a minimum graft survival and follow-up of 2.6 years. The modification of diet in renal disease equation for estimating glomerular filtration rate (eGFRMDRD) was used to calculate the slope of renal function over time using all available serum creatinine values between 1 and 5 years after transplantation. RESULTS: Most transplants demonstrated good function (eGFRMDRD ≥40 mL/min) at 1 year with positive eGFRMDRD slope between 1 and 5 years after transplantation. However, a subset of grafts with 1-year eGFRMDRD ≥40 mL/min exhibited strongly negative eGFRMDRD slope between 1 and 5 years suggestive of progressive loss of graft function. Forty-one percent of this subset reached graft failure during follow-up, accounting for 69% of allograft failures occurring after 2.5 years after transplantation. This pattern of progressive decline in estimated glomerular filtration rate despite good early function was associated with but not fully attributable to factors suggestive of enhanced antidonor immunity. CONCLUSIONS: Longitudinal analysis of serial estimated glomerular filtration ratemeasurements identifies initially well-functioning kidney transplants at high risk for subsequent graft loss. For this subset, further studies are needed to identify modifiable causes of functional decline.
    Transplantation 10/2012; · 3.78 Impact Factor
  • Matthew D Griffin
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    ABSTRACT: Mononuclear phagocytes (macrophages, dendritic cells, and monocytes) play a complex role in kidney disease. Techniques for selectively depleting them in rodents have made important contributions but have also generated some contradictory results. Ferenbach et al. report that two widely used mononuclear phagocyte depletion techniques differentially affect early severity of renal ischemia/reperfusion injury and provide evidence that this may be due to a residual, protective subset that persists in the kidney after one of the two techniques.
    Kidney International 10/2012; 82(8):835-7. · 8.52 Impact Factor
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    ABSTRACT: INTRODUCTION: The immunological and homing properties of mesenchymal stem cells (MSCs) provide a potentially attractive treatment for arthritis. The objective of this study was to determine effects of genetic disparity on the immunosuppressive potential of MSCs in vitro and in vivo within collagen induced arthritis (CIA). METHODS: The ability of DBA/1, FVB and BALB/c MSC preparations to impact the cytokine release profile of CD3/CD28 stimulated DBA/1 T cells was assessed in vitro. The effect of systemically delivered MSCs on the progression of CIA and cytokine production was assessed in vivo. RESULTS: All MSC preparations suppressed the release of TNFα and augmented the secretion of IL-4 and IL-10 by stimulated DBA/1 T-cells. However, assessment of the ratio of IFNγ to IL-4 production indicated that the more genetically distant BALB/c MSCs had significantly less immunosuppressive capacity. Systemic delivery of BALB/c MSC resulted in an exacerbation of CIA disease score in vivo and a higher erosive disease burden. This was not seen after treatment with syngeneic or partially mismatched MSCs. An increase in serum levels of IL-1β was observed up to 20 days post treatment with allogeneic MSCs. An initial elevation of IL-17 in these treatment groups persisted in those treated with fully mismatched BALB/c MSCs. Over the course of the study, there was a significant suppression of serum IL-17 levels in groups treated with syngeneic MSCs. CONCLUSIONS: These data demonstrate a significant difference in the immunosuppressive properties of syngeneic and allogeneic MSCs in vitro and in vivo, which needs to be appreciated when developing MSC based therapies for inflammatory arthritis.
    Arthritis research & therapy 07/2012; 14(4):R167. · 4.27 Impact Factor
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    Bairbre A McNicholas, Matthew D Griffin
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    ABSTRACT: Acute kidney injury triggers activation of innate immune responses and of proapoptotic programs such as the p53 pathway. Mulay et al. examine the effects of blocking murine double minute-2 (mdm2), a negative regulator of p53, using a novel chemotherapeutic agent, nutlin-3a, in mouse ischemia-reperfusion injury. Their results indicate that mdm2 promotes renal regeneration by limiting p53-mediated apoptosis but also enhances early inflammation by facilitating DNA binding of nuclear factor-κB independently of p53.
    Kidney International 06/2012; 81(12):1161-4. · 8.52 Impact Factor
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    ABSTRACT: Interleukin 17A-secreting T-helper 17 (Th17) cells are pathogenic in inflammatory kidney diseases, but their intrarenal regulation is poorly understood. In order to better define Th17 cell dynamics during interstitial inflammation, we utilized the mouse unilateral ureteral obstruction model to analyze inflammatory cell subtypes by multicolor flow cytometry and cell sorting and by effects on in vitro-generated Th17 cells. Interleukin 17A expression localized to CCR6(+)CCR4(+/-)CD4(+) T-cells and progressively increased in obstructed kidneys. The number of CCR6(+)CD4(+) T-cells increased over 10-fold by 72 h, were enriched for interleukin 17A production, and were highly proliferative based on in vivo bromodeoxyuridine incorporation. Secreted products of leukocytes isolated from obstructed kidneys enhanced the interleukin 17A production of in vitro-generated Th17 cells. This Th17-enhancing activity was identified as interleukin-1 produced by renal dendritic cells and monocytes. The in vivo validity of these findings was confirmed in mice lacking the interleulin-1 receptor and in mice treated with a recombinant interleukin-1 receptor antagonist, each of which exhibited reduced intrarenal Th17 activity compared with control mice. Thus, the inflamed kidney accumulates CCR6(+) Th17 cells that undergo activation and proliferation. Production of interleukin 1 family cytokines by resident dendritic cells and infiltrating monocytes enhances intrarenal Th17 activation in acute kidney injury.
    Kidney International 02/2012; 81(4):379-90. · 8.52 Impact Factor
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    ABSTRACT: Cell surface mucins configure the cell surface by presenting extended protein backbones that are heavily O-glycosylated. The glycopeptide structures establish physicochemical properties at the cell surface that enable and block the formation of biologically important molecular complexes. Some mucins, such as MUC1, associate with receptor tyrosine kinases and other cell surface receptors, and engage in signal transduction in order to communicate information regarding conditions at the cell surface to the nucleus. In that context, the MUC1 cytoplasmic tail (MUC1CT) receives phosphorylation signals from receptor tyrosine kinases and serine/threonine kinases, which enables its association with different signaling complexes that conduct these signals to the nucleus and perhaps other subcellular organelles. We have detected the MUC1CT at promoters of over 500 genes, in association with several different transcription factors, and have shown that promoter occupancy can vary under different growth factor conditions. However, the full biochemical nature of the nuclear forms of MUC1 and its function at these promoter regions remain undefined. I will present evidence that nuclear forms of the MUC1CT include extracellular and cytoplasmic tail domains. In addition, I will discuss evidence for a hypothesis that the MUC1CT possesses a novel catalytic function that enables remodeling of the transcription factor occupancy of promoters, and thereby engages in regulation of gene expression.
    Glycobiology 11/2011; 21(11):1454-531. · 3.54 Impact Factor

Publication Stats

4k Citations
653.75 Total Impact Points

Institutions

  • 2013
    • St. Ann's University Hospital Brno
      Brünn, South Moravian, Czech Republic
  • 2008–2013
    • National University of Ireland, Galway
      • • College of Medicine, Nursing, and Health Sciences
      • • Regenerative Medicine Institute
      • • National Centre for Biomedical Engineering Science
      Galway, C, Ireland
  • 1996–2013
    • Mayo Clinic - Rochester
      • • Department of Surgery
      • • Department of Hospital Internal Medicine
      Rochester, Minnesota, United States
  • 2009
    • University of Arkansas at Little Rock
      Little Rock, Arkansas, United States
  • 2000–2009
    • Mayo Foundation for Medical Education and Research
      • • Division of Nephrology and Hypertension
      • • Department of Surgery
      • • Department of Medicine
      • • Department of Internal Medicine
      Scottsdale, AZ, United States
  • 2006
    • Joslin Diabetes Center
      Boston, Massachusetts, United States
  • 2005
    • University of Minnesota Duluth
      Duluth, Minnesota, United States
  • 1999–2001
    • University of Chicago
      • • Committee on Immunology
      • • Department of Pathology
      Chicago, IL, United States