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

  • Hyunju, Park (Department of Physiology, Inflammation-Cancer Microenvironment Research Center) ;
  • Jung A, Shin (Department of Anatomy, Ewha Womans University College of Medicine) ;
  • Jiwoo, Lim (Department of Physiology, Inflammation-Cancer Microenvironment Research Center) ;
  • Seulgi, Lee (Department of Physiology, Inflammation-Cancer Microenvironment Research Center) ;
  • Jung-Hyuck, Ahn (Department of Biochemistry, Ewha Womans University College of Medicine) ;
  • Jihee Lee, Kang (Department of Physiology, Inflammation-Cancer Microenvironment Research Center) ;
  • Youn-Hee, Choi (Department of Physiology, Inflammation-Cancer Microenvironment Research Center)
  • 투고 : 2022.03.22
  • 심사 : 2022.10.12
  • 발행 : 2022.12.31

초록

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.

키워드

과제정보

This work was supported by a National Research Foundation of Korea (NRF) grant funded by NRF-2019R1A2B5B01070674 and 2020R1A5A2019210 (Y.-H.C.) and by the RP-Grant 2019 of Ewha Womans University (H.P.) and NRF-2021R1C1C1008860 (J.A.S.).

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