Caveolin-1 plays a critical role in the differentiation of monocytes into macrophages

Fu, Yi, Moore, Xiao-Lei, Lee, Man K. S., Fernández-Rojo, Manuel A., Parat, Marie-Odile, Parton, Robert G., Meikle, Peter J., Sviridov, Dmitri and Chin-Dusting, Jaye P. F. (2012) Caveolin-1 plays a critical role in the differentiation of monocytes into macrophages. Arteriosclerosis, Thrombosis, and Vascular Biology, 32 9: e117-e125.


Author Fu, Yi
Moore, Xiao-Lei
Lee, Man K. S.
Fernández-Rojo, Manuel A.
Parat, Marie-Odile
Parton, Robert G.
Meikle, Peter J.
Sviridov, Dmitri
Chin-Dusting, Jaye P. F.
Title Caveolin-1 plays a critical role in the differentiation of monocytes into macrophages
Journal name Arteriosclerosis, Thrombosis, and Vascular Biology  (ERA 2012 Listed)    (ERA 2010 Rank A*)   Check publisher's open access policy
Publication date 2012-09
Sub-type Article
DOI 10.1161/ATVBAHA.112.254151
Volume number 32
Issue number 9
ISSN 1079-5642; 1524-4636
Start page e117
End page e125
Total pages 9
Place of publication Philadelphia, PA, United States
Publisher Lippincott, Williams & Wilkins
Collection year 2013
Language eng
Formatted abstract Objective—Monocyte to macrophage differentiation is an essential step in atherogenesis. The structure protein of caveolae, caveolin-1, is increased in primary monocytes after its adhesion to endothelium. We explore the hypothesis that caveolin-1 plays a role in monocyte differentiation to macrophages.
Methods and Results—Both phorbol myristate acetate–induced THP-1 and colony stimulating factor–induced primary monocyte differentiation was associated with an increase in cellular caveolin-1 expression. Overexpression of caveolin-1 by transfection increased macrophage surface markers and inflammatory genes, whereas caveolin-1 knockdown by small interfering RNA or knockout reduced these. Also, caveolin-1 knockdown inhibited the differentiation–induced nuclear translocation of early growth response factor 1 (EGR-1) through ERK phosphorylation, further decreased the binding of EGR-1 to CD115 promoter, thus decreasing EGR-1 transcriptional activity. In functional assays, caveolin-1 inhibited transmigration but promoted phagocytosis in the monocyte–macrophage lineage. Decreasing caveolin-1 inhibited the uptake of modified low-density lipoprotein and reduced cellular lipid content. Finally, we showed that caveolin-1 knockout mice displayed less monocyte differentiation than wild-type mice and that EGR-1 transcription activity was also decreased in these mice because of the inhibition of ERK phosphorylation.
Conclusion—Caveolin-1 promotes monocyte to macrophage differentiation through the regulation of EGR-1 transcriptional activity, suggesting that phagocytic caveolin-1 may be critical for atherogenesis.
Keyword Caveolin-1
Monocyte differentiation
Macrophages
Early growth response factor 1
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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Created: Mon, 23 Jul 2012, 13:49:21 EST by Myrtle Sahabandu on behalf of School of Pharmacy