nach oben

Acta Neuropathologica

Erschienen in:

01.01.2010 | Original Paper

Progranulin expression is upregulated after spinal contusion in mice

verfasst von: Swati B. Naphade, Kristina A. Kigerl, Lyn B. Jakeman, Sandra K. Kostyk, Phillip G. Popovich, Jeff Kuret

Erschienen in: Acta Neuropathologica | Ausgabe 1/2010

Einloggen, um Zugang zu erhalten

Abstract

Progranulin (proepithelin) is a pleiotropic growth-factor associated with inflammation and wound repair in peripheral tissues. It also has been implicated in the response to acute traumatic brain injury as well as to chronic neurodegenerative diseases. To determine whether changes in progranulin expression also accompany acute spinal cord injury, C57BL/6 mice were subjected to mid-thoracic (T9 level) contusion spinal cord injury and analyzed by immunohistochemical and biochemical methods. Whereas spinal cord sections prepared from non-injured laminectomy control animals contained low basal levels of progranulin immunoreactivity in gray matter, sections from injured animals contained intense immunoreactivity throughout the injury epicenter that peaked 7–14 days post injury. Progranulin immunoreactivity colocalized with myeloid cell markers CD11b and CD68, indicating that expression increased primarily in activated microglia and macrophages. Immunoblot analysis confirmed that progranulin protein levels rose after injury. On the basis of quantitative polymerase chain reaction analysis, increased protein levels resulted from a tenfold rise in progranulin transcripts. These data demonstrate that progranulin is dramatically induced in myeloid cells after experimental spinal cord injury and is positioned appropriately both spatially and temporally to influence recovery after injury.

Ahmed Z, Mackenzie IR, Hutton ML, Dickson DW (2007) Progranulin in frontotemporal lobar degeneration and neuroinflammation. J Neuroinflamm 4:7CrossRef

Baba T, Hoff HB III, Nemoto H et al (1993) Acrogranin, an acrosomal cysteine-rich glycoprotein, is the precursor of the growth-modulating peptides, granulins, and epithelins, and is expressed in somatic as well as male germ cells. Mol Reprod Dev 34:233–243CrossRefPubMed

Baker CA, Manuelidis L (2003) Unique inflammatory RNA profiles of microglia in Creutzfeldt-Jakob disease. Proc Natl Acad Sci USA 100:675–679CrossRefPubMed

Baker M, Mackenzie IR, Pickering-Brown SM et al (2006) Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature 442:916–919CrossRefPubMed

Bhandari V, Daniel R, Lim PS, Bateman A (1996) Structural and functional analysis of a promoter of the human granulin/epithelin gene. Biochem J 319:441–447PubMed

Bhandari V, Palfree RG, Bateman A (1992) Isolation and sequence of the granulin precursor cDNA from human bone marrow reveals tandem cysteine-rich granulin domains. Proc Natl Acad Sci USA 89:1715–1719CrossRefPubMed

Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254CrossRefPubMed

Brouwers N, Sleegers K, Engelborghs S et al (2008) Genetic variability in progranulin contributes to risk for clinically diagnosed Alzheimer disease. Neurology 71:656–664CrossRefPubMed

Carmel JB, Kakinohana O, Mestril R, Young W, Marsala M, Hart RP (2004) Mediators of ischemic preconditioning identified by microarray analysis of rat spinal cord. Exp Neurol 185:81–96CrossRefPubMed

10.

Chen-Plotkin AS, Xiao J, Geser F et al. (2009) Brain progranulin expression in GRN-associated frontotemporal lobar degeneration. Acta Neuropathol (in press). doi:10.1007/s00401-009-0576-2

11.

Cruts M, Gijselinck I, van der Zee J et al (2006) Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21. Nature 442:920–924CrossRefPubMed

12.

Daniel R, Daniels E, He Z, Bateman A (2003) Progranulin (acrogranin/PC cell-derived growth factor/granulin-epithelin precursor) is expressed in the placenta, epidermis, microvasculature, and brain during murine development. Dev Dyn 227:593–599CrossRefPubMed

13.

Daniel R, He Z, Carmichael KP, Halper J, Bateman A (2000) Cellular localization of gene expression for progranulin. J Histochem Cytochem 48:999–1009PubMed

14.

Donnelly DJ, Gensel JC, Ankeny DP, van Rooijen N, Popovich PG (2009) An efficient and reproducible method for quantifying macrophages in different experimental models of central nervous system pathology. J Neurosci Meth 181:36–44CrossRef

15.

Donnelly DJ, Popovich PG (2008) Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury. Exp Neurol 209:378–388CrossRefPubMed

16.

Fitch MT, Silver J (2008) CNS injury, glial scars, and inflammation: Inhibitory extracellular matrices and regeneration failure. Exp Neurol 209:294–301CrossRefPubMed

17.

Hanington PC, Barreda DR, Belosevic M (2006) A novel hematopoietic granulin induces proliferation of goldfish (Carassius auratus L.) macrophages. J Biol Chem 281:9963–9970CrossRefPubMed

18.

He Z, Bateman A (2003) Progranulin (granulin-epithelin precursor, PC-cell-derived growth factor, acrogranin) mediates tissue repair and tumorigenesis. J Mol Med 81:600–612CrossRefPubMed

19.

He Z, Ong CH, Halper J, Bateman A (2003) Progranulin is a mediator of the wound response. Nat Med 9:225–229CrossRefPubMed

20.

Holness CL, da Silva RP, Fawcett J, Gordon S, Simmons DL (1993) Macrosialin, a mouse macrophage-restricted glycoprotein, is a member of the lamp/lgp family. J Biol Chem 268:9661–9666PubMed

21.

Holness CL, Simmons DL (1993) Molecular cloning of CD68, a human macrophage marker related to lysosomal glycoproteins. Blood 81:1607–1613PubMed

22.

Hrabal R, Chen Z, James S, Bennett HP, Ni F (1996) The hairpin stack fold, a novel protein architecture for a new family of protein growth factors. Nat Struct Biol 3:747–752CrossRefPubMed

23.

Jakeman LB, Guan Z, Wei P et al (2000) Traumatic spinal cord injury produced by controlled contusion in mouse. J Neurotrauma 17:299–319CrossRefPubMed

24.

Jones TB, Basso DM, Sodhi A et al (2002) Pathological CNS autoimmune disease triggered by traumatic spinal cord injury: implications for autoimmune vaccine therapy. J Neurosci 22:2690–2700PubMed

25.

Kessenbrock K, Frohlich L, Sixt M et al (2008) Proteinase 3 and neutrophil elastase enhance inflammation in mice by inactivating antiinflammatory progranulin. J Clin Invest 118:2438–2447PubMed

26.

Kigerl KA, Lai W, Rivest S, Hart RP, Satoskar AR, Popovich PG (2007) Toll-like receptor (TLR)-2 and TLR-4 regulate inflammation, gliosis, and myelin sparing after spinal cord injury. J Neurochem 102:37–50CrossRefPubMed

27.

Kigerl KA, McGaughy VM, Popovich PG (2006) Comparative analysis of lesion development and intraspinal inflammation in four strains of mice following spinal contusion injury. J Comp Neurol 494:578–594CrossRefPubMed

28.

Kojima Y, Ono K, Inoue K et al (2009) Progranulin expression in advanced human atherosclerotic plaque. Atherosclerosis 206:102–108CrossRefPubMed

29.

Kramps JA, van Twisk C, van der Linden AC (1983) l-Pyroglutamyl-l-prolyl-l-valine-p-nitroanilide, a highly specific substrate for granulocyte elastase. Scand J Clin Lab Invest 43:427–432CrossRefPubMed

30.

Kurushima H, Ramprasad M, Kondratenko N, Foster DM, Quehenberger O, Steinberg D (2000) Surface expression and rapid internalization of macrosialin (mouse CD68) on elicited mouse peritoneal macrophages. J Leukoc Biol 67:104–108PubMed

31.

Lee MK, Tuttle JB, Rebhun LI, Cleveland DW, Frankfurter A (1990) The expression and posttranslational modification of a neuron-specific beta-tubulin isotype during chick embryogenesis. Cell Motil Cytoskeleton 17:118–132CrossRefPubMed

32.

Li G, Yin H, Kuret J (2004) Casein kinase 1 delta phosphorylates tau and disrupts its binding to microtubules. J Biol Chem 279:15938–15945CrossRefPubMed

33.

Li X, Massa PE, Hanidu A et al (2002) IKKalpha, IKKbeta, and NEMO/IKKgamma are each required for the NF-kappa B-mediated inflammatory response program. J Biol Chem 277:45129–45140CrossRefPubMed

34.

Liu NK, Xu XM (2006) β-Tubulin is a more suitable internal control than β-actin in western blot analysis of spinal cord tissues after traumatic injury. J Neurotrauma 23:1794–1801CrossRefPubMed

35.

Ma M, Basso DM, Walters P, Stokes BT, Jakeman LB (2001) Behavioral and histological outcomes following graded spinal cord contusion injury in the C57Bl/6 mouse. Exp Neurol 169:239–254CrossRefPubMed

36.

Mackenzie IR, Baker M, Pickering-Brown S et al (2006) The neuropathology of frontotemporal lobar degeneration caused by mutations in the progranulin gene. Brain 129:3081–3090CrossRefPubMed

37.

Malaspina A, Kaushik N, de Belleroche J (2001) Differential expression of 14 genes in amyotrophic lateral sclerosis spinal cord detected using gridded cDNA arrays. J Neurochem 77:132–145PubMedCrossRef

38.

Matzilevich DA, Rall JM, Moore AN, Grill RJ, Dash PK (2002) High-density microarray analysis of hippocampal gene expression following experimental brain injury. J Neurosci Res 67:646–663CrossRefPubMed

39.

Moisse K, Volkening K, Leystra-Lantz C, Welch I, Hill T, Strong MJ (2009) Divergent patterns of cytosolic TDP-43 and neuronal progranulin expression following axotomy: implications for TDP-43 in the physiological response to neuronal injury. Brain Res 1249:202–211CrossRefPubMed

40.

Mukherjee O, Pastor P, Cairns NJ et al (2006) HDDD2 is a familial frontotemporal lobar degeneration with ubiquitin-positive, tau-negative inclusions caused by a missense mutation in the signal peptide of progranulin. Ann Neurol 60:314–322CrossRefPubMed

41.

Ohmi K, Greenberg DS, Rajavel KS, Ryazantsev S, Li HH, Neufeld EF (2003) Activated microglia in cortex of mouse models of mucopolysaccharidoses I and IIIB. Proc Natl Acad Sci USA 100:1902–1907CrossRefPubMed

42.

Pereson S, Wils H, Kleinberger G et al (2009) Progranulin expression correlates with dense-core amyloid plaque burden in Alzheimer disease mouse models. J Pathol 219:173–181CrossRefPubMed

43.

Plowman GD, Green JM, Neubauer MG et al (1992) The epithelin precursor encodes two proteins with opposing activities on epithelial cell growth. J Biol Chem 267:13073–13078PubMed

44.

Popovich PG, Hickey WF (2001) Bone marrow chimeric rats reveal the unique distribution of resident and recruited macrophages in the contused rat spinal cord. J Neuropathol Exp Neurol 60:676–685PubMed

45.

Popovich PG, Wei P, Stokes BT (1997) Cellular inflammatory response after spinal cord injury in Sprague-Dawley and Lewis rats. J Comp Neurol 377:443–464CrossRefPubMed

46.

Qin J, Diaz-Cueto L, Schwarze JE et al (2005) Effects of progranulin on blastocyst hatching and subsequent adhesion and outgrowth in the mouse. Biol Reprod 73:434–442CrossRefPubMed

47.

Ririe KM, Rasmussen RP, Wittwer CT (1997) Product differentiation by analysis of DNA melting curves during the polymerase chain reaction. Anal Biochem 245:154–160CrossRefPubMed

48.

Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 3:1101–1108CrossRefPubMed

49.

Schnell L, Fearn S, Klassen H, Schwab ME, Perry VH (1999) Acute inflammatory responses to mechanical lesions in the CNS: differences between brain and spinal cord. Eur J Neurosci 11:3648–3658CrossRefPubMed

50.

Schroeder A, Mueller O, Stocker S et al (2006) The RIN: an RNA integrity number for assigning integrity values to RNA measurements. BMC Mol Biol 7:3CrossRefPubMed

51.

Shankaran SS, Capell A, Hruscha AT et al (2008) Missense mutations in the progranulin gene linked to frontotemporal lobar degeneration with ubiquitin-immunoreactive inclusions reduce progranulin production and secretion. J Biol Chem 283:1744–1753CrossRefPubMed

52.

Sleegers K, Brouwers N, Maurer-Stroh S et al (2008) Progranulin genetic variability contributes to amyotrophic lateral sclerosis. Neurology 71:253–259CrossRefPubMed

53.

Solovjov DA, Pluskota E, Plow EF (2005) Distinct roles for the alpha and beta subunits in the functions of integrin alphaMbeta2. J Biol Chem 280:1336–1345CrossRefPubMed

54.

Sparro G, Galdenzi G, Eleuteri AM, Angeletti M, Schroeder W, Fioretti E (1997) Isolation and N-terminal sequence of multiple forms of granulins in human urine. Protein Expr Purif 10:169–174CrossRefPubMed

55.

Sroga JM, Jones TB, Kigerl KA, McGaughy VM, Popovich PG (2003) Rats and mice exhibit distinct inflammatory reactions after spinal cord injury. J Comp Neurol 462:223–240CrossRefPubMed

56.

Tonai T, Shiba K, Taketani Y et al (2001) A neutrophil elastase inhibitor (ONO-5046) reduces neurologic damage after spinal cord injury in rats. J Neurochem 78:1064–1072CrossRefPubMed

57.

Van Damme P, Van Hoecke A, Lambrechts D et al (2008) Progranulin functions as a neurotrophic factor to regulate neurite outgrowth and enhance neuronal survival. J Cell Biol 181:37–41CrossRefPubMed

58.

van der Zee J, Le Ber I, Maurer-Stroh S et al (2007) Mutations other than null mutations producing a pathogenic loss of progranulin in frontotemporal dementia. Hum Mutat 28:416PubMed

59.

Youn BS, Bang SI, Kloting N et al (2009) Serum progranulin concentrations may be associated with macrophage infiltration into omental adipose tissue. Diabetes 58:627–636CrossRefPubMed

60.

Young W (2002) Spinal cord contusion models. Prog Brain Res 137:231–255CrossRefPubMed

61.

Zhou J, Gao G, Crabb JW, Serrero G (1993) Purification of an autocrine growth factor homologous with mouse epithelin precursor from a highly tumorigenic cell line. J Biol Chem 268:10863–10869PubMed

62.

Zhu J, Nathan C, Jin W et al (2002) Conversion of proepithelin to epithelins: roles of SLPI and elastase in host defense and wound repair. Cell 111:867–878CrossRefPubMed

Titel: Progranulin expression is upregulated after spinal contusion in mice
verfasst von: Swati B. Naphade
Kristina A. Kigerl
Lyn B. Jakeman
Sandra K. Kostyk
Phillip G. Popovich
Jeff Kuret
Publikationsdatum: 01.01.2010
Verlag: Springer-Verlag
Erschienen in: Acta Neuropathologica / Ausgabe 1/2010
Print ISSN: 0001-6322
Elektronische ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-009-0616-y

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Frühe Alzheimertherapie lohnt sich

25.04.2024 AAN-Jahrestagung 2024 Nachrichten

Ist die Tau-Last noch gering, scheint der Vorteil von Lecanemab besonders groß zu sein. Und beginnen Erkrankte verzögert mit der Behandlung, erreichen sie nicht mehr die kognitive Leistung wie bei einem früheren Start. Darauf deuten neue Analysen der Phase-3-Studie Clarity AD.

Viel Bewegung in der Parkinsonforschung

25.04.2024 Parkinson-Krankheit Nachrichten

Neue arznei- und zellbasierte Ansätze, Frühdiagnose mit Bewegungssensoren, Rückenmarkstimulation gegen Gehblockaden – in der Parkinsonforschung tut sich einiges. Auf dem Deutschen Parkinsonkongress ging es auch viel um technische Innovationen.

Demenzkranke durch Antipsychotika vielfach gefährdet

23.04.2024 Demenz Nachrichten

Wenn Demenzkranke aufgrund von Symptomen wie Agitation oder Aggressivität mit Antipsychotika behandelt werden, sind damit offenbar noch mehr Risiken verbunden als bislang angenommen.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2010

Kurt Jellinger Prize 2010 for Outstanding Scientific Writing in Neuropathology

Astrocytes: biology and pathology

The enigmatic roles of microglial versus neuronal progranulin in neurological disease

Ependymal cells: biology and pathology

Oligodendrocytes: biology and pathology