Page 9 - A. Aging

miR-223-3p regulates TLR4-dependent endothelial senescence by targeting HDAC2
Hyo-Jin Kim, Bo-Gyeong Seo and Cheol Hwangbo
Division of Life Science, College of Natural Sciences and Division of Applied Life Science (BK21 Plus), PMBBRC, Gyeongsang National University,
Jinju 52828,, Republic of Korea

BACKGROUND AIM
HDAC expression and activity is decreased in severe COPD patients We had previously reported that innate immune receptor
and in smokers versus normal and non-smokers, particularly HDAC2 toll-like receptor 4 (TLR4) is a critical regulator of
expression has changed meaningfully. Downregulation of HDAC2 endothelial cell senescence through modification of
expression using inhibitor or siRNA is induced loss of alveolar septal cell
which typical phenotype of emphysema in human pulmonary histone acetylation by HDAC2 in age-induced emphysema
microvascular endothelial cells (HPMVEC) and mice. However, the molecular mechanism of HDAC2 in
regulating aging and cellular senescence remained
miRNA-223 is first characterized as regulator of granulocyte
differentiation in hematopoietic system and it is reported that reversibly unclear. Thus, we studied that HDAC2 regulation
regulator of erythroid differentiation. miR-223 is related various disease, mechanism using cigarette smoke extract (CSE), the main
such as cancer, rheumatoid arthritis, and emphysema. cause of emphysema.
METHODS
We processed gene expression analysis to obtain candidates expect as HDAC2 regulation in endothelial cell. Next, we
checked the expression change using real-time PCR. To measure the degree of senescence, we implemented SA-beta-
gal staining. This makes the cell look blue in response to beta-galactosidase, which high activity in senescent cells.

RESULTS

Figure1. CSE reduces expression of TLR4 and HDAC2
and induces cell senescence. Figure2. miR-223 directly targets HDAC2.

Figure 3. miR-223-mimic regulates Figure 4. miR-223 regulates cell senescence induced by
cell senescence in endothelial cells. TLR4 knock-down

CONCLUSION REFERENCES

Ito, K., M. Ito, et al. (2005). "Decreased histone deacetylase activity in chronic
obstructive pulmonary disease." N Engl J Med.

Kim, S. J., P. Shan, et al. (2019). "Endothelial toll-like receptor 4 maintains lung integrity
via epigenetic suppression of p16(INK4a)." Aging Cell.
Bartel, D. P. (2009). "MicroRNAs: target recognition and regulatory functions." Cell.

Contact
A proposed pathway for cell senescence Hyo-Jin Kim E-mail : jin4477@hanmail.net
regulated by miR-223 in endothelial cells. information