Kuei-Chun Wang - UCSB College of Engineering

richessewoozyBiotechnology

Oct 1, 2013 (3 years and 8 months ago)

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Flow Regulation of miRNAs in Endothelial Functions


Kuei
-
Chun Wang, Jing Zhou, Yi
-
Shuan Li,
and
Shu Chien


Department

of Bioengineering,

U
niversity of California at San Diego
,
La Jolla, CA
92093
-
0412



Tel:

858
-
534
-
5195

E
-
mail:
shuchien@ucsd.edu





The differential effects of flow patterns play important roles in regulating the vascular endothelial cells functions
(ECs). Focal nature of atherosclerotic plaque formation reveals that the pulsatile flow (PS) along the straight part of
arterial tree exer
ts the athero
-
protective effect on the ECs, while the disturbed flow characterized as the oscillatory
flow (OS) found at the arterial bifurcation stimulates the pro
-
inflammatory response.
Recent discovery of miRNAs
reveals a novel powerful mechanism for po
st
-
transcriptional control of gene expression and modulate many
biological processes.

However, the roles of miRNAs in regulating mechano
-
transduction and EC functions remain
unclear. Using genome
-
wide microarray study, we profiled miRNA and mRNA expression

levels

in human ECs
under 24
-
hr PS and OS flow, as well as the static control. Bioinformatics analyses of mRNA profiles indicated that
PS predominantly regulates EC growth arrest, while as OS modulates EC inflammatory response. Further miRNA
studies show
that PS suppresses EC growth through the regulation of miR
-
23b on cell cycle machinery, and
inhibition of miR
-
23b expression using antagomir
-
23b oligonucleotide attenuated the PS
-
induced G1/G0 cell cycle
arrest. Conversely, OS causes sustained expression o
f miR
-
21

to contribut
e to pro
-
inflammatory re
sponse by
targeting PPAR
-
alpha.

In conclusion,
o
ur results demonstrate that miRNA

expression level can be differentially
regulated by different flow patterns, consequently modulating the EC functions related to EC growth and
inflammation.