Lipocalin-2 is an autocrine mediator of reactive astrocytosis

Shinrye Lee, Jae-Yong Park, Won Ha Lee, Ho Kim, Hae Chul Park, Kiyoshi Mori, Kyoungho Suk

Research output: Contribution to journalArticle

125 Citations (Scopus)

Abstract

Astrocytes, the most abundant glial cell type in the brain, provide metabolic and trophic support to neurons and modulate synaptic activity. In response to a brain injury, astrocytes proliferate and become hypertrophic with an increased expression of intermediate filament proteins. This process is collectively referred to as reactive astrocytosis. Lipocalin 2 (lcn2) is amemberof the lipocalin family that binds to small hydrophobic molecules. We propose that lcn2 is an autocrine mediator of reactive astrocytosis based on the multiple roles of lcn2 in the regulation of cell death, morphology, and migration of astrocytes. lcn2 expression and secretion increased after inflammatory stimulation in cultured astrocytes. Forced expression of lcn2 or treatment with LCN2 protein increased the sensitivity of astrocytes to cytotoxic stimuli. Iron and BIM (Bcl-2-interacting mediator of cell death) proteins were involved in the cytotoxic sensitization process. LCN2 protein induced upregulation of glial fibrillary acidic protein (GFAP), cell migration, and morphological changes similar to characteristic phenotypic changes termed reactive astrocytosis. The lcn2-induced phenotypic changes of astrocytes occurred through a Rho-ROCK (Rho kinase)-GFAP pathway, which was positively regulated by nitric oxide and cGMP. In zebrafishes, forced expression of rat lcn2 gene increased the number and thickness of cellular processes in GFAP-expressing radial glia cells, suggesting that lcn2 expression in glia cells plays an important role in vivo. Our results suggest that lcn2 acts in an autocrine manner to induce cell death sensitization and morphological changes in astrocytes under inflammatory conditions and that these phenotypic changes may be the basis of reactive astrocytosis in vivo.

Original languageEnglish
Pages (from-to)234-249
Number of pages16
JournalJournal of Neuroscience
Volume29
Issue number1
DOIs
Publication statusPublished - 2009 Jan 7

Fingerprint

Gliosis
Astrocytes
Glial Fibrillary Acidic Protein
Neuroglia
Cell Movement
Cell Death
Lipocalins
Intermediate Filament Proteins
rho-Associated Kinases
Proteins
Lipocalin-2
Zebrafish
Brain Injuries
Nitric Oxide
Up-Regulation
Iron
Neurons
Brain

Keywords

  • Astrocyte
  • Astrocytosis
  • Glial fibrillary acidic protein
  • Lipocalin 2
  • Neuroinflammation
  • Zebrafish

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Lipocalin-2 is an autocrine mediator of reactive astrocytosis. / Lee, Shinrye; Park, Jae-Yong; Lee, Won Ha; Kim, Ho; Park, Hae Chul; Mori, Kiyoshi; Suk, Kyoungho.

In: Journal of Neuroscience, Vol. 29, No. 1, 07.01.2009, p. 234-249.

Research output: Contribution to journalArticle

Lee, Shinrye ; Park, Jae-Yong ; Lee, Won Ha ; Kim, Ho ; Park, Hae Chul ; Mori, Kiyoshi ; Suk, Kyoungho. / Lipocalin-2 is an autocrine mediator of reactive astrocytosis. In: Journal of Neuroscience. 2009 ; Vol. 29, No. 1. pp. 234-249.
@article{2e1b2f26c84c4413a91278352812149f,
title = "Lipocalin-2 is an autocrine mediator of reactive astrocytosis",
abstract = "Astrocytes, the most abundant glial cell type in the brain, provide metabolic and trophic support to neurons and modulate synaptic activity. In response to a brain injury, astrocytes proliferate and become hypertrophic with an increased expression of intermediate filament proteins. This process is collectively referred to as reactive astrocytosis. Lipocalin 2 (lcn2) is amemberof the lipocalin family that binds to small hydrophobic molecules. We propose that lcn2 is an autocrine mediator of reactive astrocytosis based on the multiple roles of lcn2 in the regulation of cell death, morphology, and migration of astrocytes. lcn2 expression and secretion increased after inflammatory stimulation in cultured astrocytes. Forced expression of lcn2 or treatment with LCN2 protein increased the sensitivity of astrocytes to cytotoxic stimuli. Iron and BIM (Bcl-2-interacting mediator of cell death) proteins were involved in the cytotoxic sensitization process. LCN2 protein induced upregulation of glial fibrillary acidic protein (GFAP), cell migration, and morphological changes similar to characteristic phenotypic changes termed reactive astrocytosis. The lcn2-induced phenotypic changes of astrocytes occurred through a Rho-ROCK (Rho kinase)-GFAP pathway, which was positively regulated by nitric oxide and cGMP. In zebrafishes, forced expression of rat lcn2 gene increased the number and thickness of cellular processes in GFAP-expressing radial glia cells, suggesting that lcn2 expression in glia cells plays an important role in vivo. Our results suggest that lcn2 acts in an autocrine manner to induce cell death sensitization and morphological changes in astrocytes under inflammatory conditions and that these phenotypic changes may be the basis of reactive astrocytosis in vivo.",
keywords = "Astrocyte, Astrocytosis, Glial fibrillary acidic protein, Lipocalin 2, Neuroinflammation, Zebrafish",
author = "Shinrye Lee and Jae-Yong Park and Lee, {Won Ha} and Ho Kim and Park, {Hae Chul} and Kiyoshi Mori and Kyoungho Suk",
year = "2009",
month = "1",
day = "7",
doi = "10.1523/JNEUROSCI.5273-08.2009",
language = "English",
volume = "29",
pages = "234--249",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "1",

}

TY - JOUR

T1 - Lipocalin-2 is an autocrine mediator of reactive astrocytosis

AU - Lee, Shinrye

AU - Park, Jae-Yong

AU - Lee, Won Ha

AU - Kim, Ho

AU - Park, Hae Chul

AU - Mori, Kiyoshi

AU - Suk, Kyoungho

PY - 2009/1/7

Y1 - 2009/1/7

N2 - Astrocytes, the most abundant glial cell type in the brain, provide metabolic and trophic support to neurons and modulate synaptic activity. In response to a brain injury, astrocytes proliferate and become hypertrophic with an increased expression of intermediate filament proteins. This process is collectively referred to as reactive astrocytosis. Lipocalin 2 (lcn2) is amemberof the lipocalin family that binds to small hydrophobic molecules. We propose that lcn2 is an autocrine mediator of reactive astrocytosis based on the multiple roles of lcn2 in the regulation of cell death, morphology, and migration of astrocytes. lcn2 expression and secretion increased after inflammatory stimulation in cultured astrocytes. Forced expression of lcn2 or treatment with LCN2 protein increased the sensitivity of astrocytes to cytotoxic stimuli. Iron and BIM (Bcl-2-interacting mediator of cell death) proteins were involved in the cytotoxic sensitization process. LCN2 protein induced upregulation of glial fibrillary acidic protein (GFAP), cell migration, and morphological changes similar to characteristic phenotypic changes termed reactive astrocytosis. The lcn2-induced phenotypic changes of astrocytes occurred through a Rho-ROCK (Rho kinase)-GFAP pathway, which was positively regulated by nitric oxide and cGMP. In zebrafishes, forced expression of rat lcn2 gene increased the number and thickness of cellular processes in GFAP-expressing radial glia cells, suggesting that lcn2 expression in glia cells plays an important role in vivo. Our results suggest that lcn2 acts in an autocrine manner to induce cell death sensitization and morphological changes in astrocytes under inflammatory conditions and that these phenotypic changes may be the basis of reactive astrocytosis in vivo.

AB - Astrocytes, the most abundant glial cell type in the brain, provide metabolic and trophic support to neurons and modulate synaptic activity. In response to a brain injury, astrocytes proliferate and become hypertrophic with an increased expression of intermediate filament proteins. This process is collectively referred to as reactive astrocytosis. Lipocalin 2 (lcn2) is amemberof the lipocalin family that binds to small hydrophobic molecules. We propose that lcn2 is an autocrine mediator of reactive astrocytosis based on the multiple roles of lcn2 in the regulation of cell death, morphology, and migration of astrocytes. lcn2 expression and secretion increased after inflammatory stimulation in cultured astrocytes. Forced expression of lcn2 or treatment with LCN2 protein increased the sensitivity of astrocytes to cytotoxic stimuli. Iron and BIM (Bcl-2-interacting mediator of cell death) proteins were involved in the cytotoxic sensitization process. LCN2 protein induced upregulation of glial fibrillary acidic protein (GFAP), cell migration, and morphological changes similar to characteristic phenotypic changes termed reactive astrocytosis. The lcn2-induced phenotypic changes of astrocytes occurred through a Rho-ROCK (Rho kinase)-GFAP pathway, which was positively regulated by nitric oxide and cGMP. In zebrafishes, forced expression of rat lcn2 gene increased the number and thickness of cellular processes in GFAP-expressing radial glia cells, suggesting that lcn2 expression in glia cells plays an important role in vivo. Our results suggest that lcn2 acts in an autocrine manner to induce cell death sensitization and morphological changes in astrocytes under inflammatory conditions and that these phenotypic changes may be the basis of reactive astrocytosis in vivo.

KW - Astrocyte

KW - Astrocytosis

KW - Glial fibrillary acidic protein

KW - Lipocalin 2

KW - Neuroinflammation

KW - Zebrafish

UR - http://www.scopus.com/inward/record.url?scp=58149400146&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58149400146&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.5273-08.2009

DO - 10.1523/JNEUROSCI.5273-08.2009

M3 - Article

VL - 29

SP - 234

EP - 249

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 1

ER -