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Int J Clin Exp Pathol 2013;6(4):660-668

Original Article
A RTK-based functional RNAi screen reveals determinants of PTX-3 expression

Hua Liu, Xin-Kai Qu, Fang Yuan, Min Zhang, Wei-Yi Fang

Department of Cardiology, Shanghai Chest Hospital affiliated to Shanghai JiaoTong University, Shanghai, China. These authors contributed
equally to this work.

Received January 30, 2013; Accepted February 15, 2013; Epub March 15, 2013; Published April 1, 2013

Abstract: Aim: The aim of the present study was to explore the role of receptor tyrosine kinases (RTKs) in the regulation of expression of PTX-3,
a protector in atherosclerosis. Methods: Human monocytic U937 cells were infected with a shRNA lentiviral vector library targeting human RTKs
upon LPS stimuli and PTX-3 expression was determined by ELISA analysis. The involvement of downstream signaling in the regulation of
PTX-3 expression was analyzed by both Western blotting and ELISA assay. Results: We found that knocking down of ERBB2/3, EPHA7, FGFR3
and RET impaired PTX-3 expression without effects on cell growth or viability. Moreover, inhibition of AKT, the downstream effector of ERBB2/3,
also reduced PTX-3 expression. Furthermore, we showed that FGFR3 inhibition by anti-cancer drugs attenuated p38 activity, in turn induced a
reduction of PTX-3 expression. Conclusion: Altogether, our study demonstrates the role of RTKs in the regulation of PTX-3 expression and
uncovers a potential cardiotoxicity effect of RTK inhibitor treatments in cancer patients who have symptoms of atherosclerosis or are at the risk
of atherosclerosis. (IJCEP1301062).

Keywords: PTX-3, RNAi screening, RTKs, target therapy, cardiotoxicity, atherosclerosis

Address correspondence to: Dr. Wei-Yi Fang, Department of Cardiology, Shanghai Chest Hospital affiliated to Shanghai JiaoTong University,
Shanghai, China. E-mail: fwyxkchest@126.com