BMP-responsive protease HtrA1 is differentially expressed in astrocytes and regulates astrocytic development and injury response

Jessie Chen, Stephanie Van Gulden, Tammy L. McGuire, Andrew C. Fleming, Chio Oka, John Kessler, Chian-Yu Peng*

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Astrocytes perform a wide array of physiological functions, including structural support, ion exchange, and neurotransmitter uptake. Despite this diversity, molecular markers that label subpopulations of astrocytes are limited, and mechanisms that generate distinct astrocyte subtypes remain unclear. Here we identified serine protease high temperature requirement A 1 (HtrA1), a bone morphogenetic protein 4 signaling regulated protein, as a novel marker of forebrain astrocytes, but not of neural stem cells, in adult mice of both sexes. Genetic deletion of HtrA1 during gliogenesis accelerates astrocyte differentiation. In addition, ablation of HtrA1 in cultured astrocytes leads to altered chondroitin sulfate proteoglycan expression and inhibition of neurite extension, along with elevated levels of transforming growth factor-β family proteins. Brain injury induces HtrA1 expression in reactive astrocytes, and loss of HtrA1 leads to an impairment in wound closure accompanied by increased proliferation of endothelial and immune cells. Our findings demonstrate that HtrA1 is differentially expressed in adult mouse forebrain astrocytes, and that HtrA1 plays important roles in astrocytic development and injury response.

Original languageEnglish (US)
Pages (from-to)3840-3857
Number of pages18
JournalJournal of Neuroscience
Volume38
Issue number15
DOIs
StatePublished - Apr 11 2018

Fingerprint

Astrocytes
Peptide Hydrolases
Temperature
Wounds and Injuries
Prosencephalon
Bone Morphogenetic Protein 4
Chondroitin Sulfate Proteoglycans
Neural Stem Cells
Ion Exchange
Transforming Growth Factors
Serine Proteases
Neurites
Brain Injuries
Neurotransmitter Agents
Proteins
Endothelial Cells

Keywords

  • Astrocyte heterogeneity
  • Bone morphogenetic protein
  • Brain injury
  • Cerebrovascular disease
  • Gliogenesis
  • HtrA1

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Chen, Jessie ; Van Gulden, Stephanie ; McGuire, Tammy L. ; Fleming, Andrew C. ; Oka, Chio ; Kessler, John ; Peng, Chian-Yu. / BMP-responsive protease HtrA1 is differentially expressed in astrocytes and regulates astrocytic development and injury response. In: Journal of Neuroscience. 2018 ; Vol. 38, No. 15. pp. 3840-3857.
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BMP-responsive protease HtrA1 is differentially expressed in astrocytes and regulates astrocytic development and injury response. / Chen, Jessie; Van Gulden, Stephanie; McGuire, Tammy L.; Fleming, Andrew C.; Oka, Chio; Kessler, John; Peng, Chian-Yu.

In: Journal of Neuroscience, Vol. 38, No. 15, 11.04.2018, p. 3840-3857.

Research output: Contribution to journalArticle

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