Oncotarget

Research Papers: Pathology:

Bradykinin regulates cell growth and migration in cultured human cardiac c-Kit+ progenitor cells

Gang Li, Yan Wang _ and Gui-Rong Li

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Oncotarget. 2017; 8:10822-10835. https://doi.org/10.18632/oncotarget.14609

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Abstract

Gang Li1,2, Yan Wang1 and Gui-Rong Li1,2

1 Xiamen Cardiovascular Hospital, Xiamen University, Xiamen, Fujian, China

2 Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong, China

Correspondence to:

Yan Wang, email:

Gui-Rong Li, email:

Keywords: Bradykinin; bradykinin receptor 2; human cardiac c-Kit+ progenitor cells; proliferation; migration; Pathology Section

Received: June 27, 2016 Accepted: January 06, 2017 Published: January 12, 2017

Abstract

Bradykinin is a well-known endogenous vasoactive peptide. The present study investigated the bradykinin receptor expression in human cardiac c-Kit+ progenitor cells and the potential role of bradykinin in regulating cell cycling progression and mobility. It was found that mRNA and protein of bradykinin type 2 receptors, but not bradykinin type 1 receptors, were abundant in cultured human cardiac c-Kit+ progenitor cells. Bradykinin (1-10 nM) stimulated cell growth and migration in a concentration-dependent manner. The increase of cell proliferation was related to promoting G0/G1 transition into G2/M and S phase. Western blots revealed that bradykinin significantly increased pAkt and pERK1/2 as well as cyclin D1, which were countered by HOE140 (an antagonist of bradykinin type 2 receptors) or by silencing bradykinin type 2 receptors. The increase of pAkt, pERK1/2 and cyclin D1 by bradykinin was prevented by the PI3K inhibitor Ly294002, the PLC inhibitors U73122 and neomycin, and/or the PKC inhibitor chelerythrine and the MAPK inhibitor PD98059. Our results demonstrate the novel information that bradykinin promotes cell cycling progression and migration in human cardiac c-Kit+ progenitor cells via activating PI3K, PLC, PKC, cyclin D1, pERK1/2, and pAkt.


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PII: 14609