Increased Caveolin-2 Expression in Brain Endothelial Cells Promotes Age-Related Neuroinflammation

Hyunju Park, Jung A. Shin, Jiwoo Lim, Seulgi Lee, Jung Hyuck Ahn, Jihee Lee Kang, Youn Hee Choi

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Aging is a major risk factor for common neurodegenerative diseases. Although multiple molecular, cellular, structural, and functional changes occur in the brain during aging, the involvement of caveolin-2 (Cav-2) in brain ageing remains unknown. We investigated Cav-2 expression in brains of aged mice and its effects on endothelial cells. The human umbilical vein endothelial cells (HUVECs) showed decreased THP-1 adhesion and infiltration when treated with Cav-2 siRNA compared to control siRNA. In contrast, Cav-2 overexpression increased THP-1 adhesion and infiltration in HUVECs. Increased expression of Cav-2 and iba-1 was observed in brains of old mice. Moreover, there were fewer iba-1–positive cells in the brains of aged Cav-2 knockout (KO) mice than of wild-type aged mice. The levels of several chemokines were higher in brains of aged wild-type mice than in young wild-type mice; moreover, chemokine levels were significantly lower in brains of young mice as well as aged Cav-2 KO mice than in their wild-type counterparts. Expression of PECAM1 and VE-cadherin proteins increased in brains of old wild-type mice but was barely detected in brains of young wild-type and Cav-2 KO mice. Collectively, our results suggest that Cav-2 expression increases in the endothelial cells of aged brain, and promotes leukocyte infiltration and age-associated neuroinflammation.

Original languageEnglish
Pages (from-to)950-962
Number of pages13
JournalMolecules and Cells
Volume45
Issue number12
DOIs
StatePublished - 31 Dec 2022

Bibliographical note

Publisher Copyright:
© The Korean Society for Molecular and Cellular Biology.

Keywords

  • aging
  • cav2 mouse
  • caveolin-2
  • endothelial cell
  • neuroinflammation

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