Page 10 - A. Aging

[A. Aging-6]

miR-223-3p regulates TLR4-dependent endothelial

senescence by targeting HDAC2

Hyo-jin Kim¹˙², Seo-bo Gyeong¹˙², Patty J. Lee³, Cheol Hwangbo¹˙²

¹Division of Life Science, Gyeongsang National University, Jinju 52828, Korea, ²Division of Applied Life Science

(BK21 Plus), Gyeongsang National University, Jinju 52828, Korea, ³Pulmonary, Critical Care and Sleep Medicine,
Department of Internal Medicine Yale University School of Medicine, New Haven CT 06520-8, USA

We had previously reported that innate immune receptor toll-like receptor 4 (TLR4) is a critical regulator of

endothelial cell senescence through modification of histone acetylation by HDAC2 in age-induced emphysema.

However, the molecular mechanism of HDAC2 in regulating aging and cellular senescence remained unclear. Using
cigarette smoke extract (CSE), the main cause of emphysema, we demonstrate that TLR4 and HDAC2 expression
was reduced, and cellular senescence was induced in response to CSE in HUVECs like as emphysematous endothelial

cells (Ec) or aged cells. The expression level of microRNAs in COPD patient and normal lung tissues were analyzed
using bioinformatical analysis, miR-223 expression was found to be the most increased in COPD patient lung

compared to normal. miR-223-3p mimic is increasing p16INK4A expression and subsequently cell cycle arrest and
cellular senescence, whereas miR-223-3p silencing decreased HDAC2 and p16INK4a, and prevent cellular senescence

in context of Ec-aging. These findings demonstrate that miR-223-3p act as an important regulator of cellular
senescence by targeting HDAC2; thus providing a novel function into previously unrecognized links between

microRNA and cellular senescence in emphysema.