Increased Caveolin-2 Expression in Brain Endothelial Cells Promotes Age-Related Neuroinflammation
Overview
Molecular Biology
Affiliations
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.
Lee C, Jang S, Lim J, Park H, Ahn S, Park S Exp Mol Med. 2025; 57(1):235-248.
PMID: 39833561 PMC: 11799301. DOI: 10.1038/s12276-024-01388-8.
Distinct, common and synergistic effects of insulin and IGF-1 receptors on healthy murine ageing.
Walker A, Watt N, Yuldasheva N, Dalmia S, Conning-Rowland M, Cheng C Heliyon. 2024; 10(16):e36457.
PMID: 39247377 PMC: 11379992. DOI: 10.1016/j.heliyon.2024.e36457.
Physiological and pathological roles of caveolins in the central nervous system.
Badaut J, Blochet C, Obenaus A, Hirt L Trends Neurosci. 2024; 47(8):651-664.
PMID: 38972795 PMC: 11324375. DOI: 10.1016/j.tins.2024.06.003.
The Recent Advances in the Function and Mechanism of Caveolin-1 in Retinal Neovascularization.
Zhang R, Dang Y Curr Drug Targets. 2024; 25(7):465-472.
PMID: 38591209 DOI: 10.2174/0113894501310201240403065930.
DAlessio A Cells. 2023; 12(23).
PMID: 38067108 PMC: 10705299. DOI: 10.3390/cells12232680.