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Hypoxia Upregulates ErbB Family Members in Human Pulmonary Microvascular Endothelial Cells
Author(s) -
Regan Christopher S.,
Jin Yi,
Pool Caitlyn S.,
Liu Yusen S.,
Chen Bernadette S.,
Nelin Leif D.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.917.6
Subject(s) - erbb , erbb3 , erbb4 , epidermal growth factor , hypoxia (environmental) , epidermal growth factor receptor , biology , microbiology and biotechnology , cancer research , vascular endothelial growth factor , signal transduction , angiogenesis , receptor , chemistry , receptor tyrosine kinase , biochemistry , vegf receptors , organic chemistry , oxygen
Pulmonary hypertension is associated with vascular remodeling that is driven by proliferation of cells in the vascular wall, which involves both endothelial cells and vascular smooth muscle cells. We have previously shown that human pulmonary microvascular endothelial cells (hPMVEC) proliferate in hypoxia, and that hypoxia results in a significant increase in the expression of both epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR/ErbB1). Furthermore, we have shown that hypoxia‐induced proliferation of hPMVEC depends on activation of EGFR/ErbB1. The literature suggests that EGFR/ErbB1 is activated via dimerization, either homodimerization (between the same ErbB family member such as ErbB1:ErbB1), or heterodimerization (between different ErbB family members such as ErbB1:ErbB2). In other cell types, ErbB1, 2, 3 and 4 have been described and the manner by which the ErbB family members dimerize may determine which down‐stream signaling cascades are activated. At present, it is not known in hPMVEC whether all ErbB family members are expressed. As a first step in understanding how ErbB is activated in hPMVEC, we tested the hypothesis that ErbB2, 3, and 4 are expressed in hPMVEC. To begin to address our hypothesis, we incubated hPMVEC in normoxia (21% O 2 , 5% CO 2 ) at 37° C for 24 hours. Protein was harvested for Western blotting and probed for ErbB1, ErbB2, ErbB3, and ErbB4. We found that hPMVEC express ErbB1, ErbB2, and ErbB4 with only minimal protein expression of ErbB3. To determine the effect of hypoxia on ErbB2 and/or ErbB4 protein expression, hPMVEC were incubated in normoxia or hypoxia (1% O2, 5% CO2) at 37° C for 24 hours. We found that protein levels of both ErbB2 and ErbB4 were greater in hypoxia than in normoxia. In conclusion, our data demonstrate that under the conditions of these experiments, hPMVEC express ErbB1, ErbB2 and ErbB4 protein, with little expression of ErbB3 protein. In addition, hypoxia enhanced ErbB2 and ErbB4 protein expression. These results have important implications for ErbB‐mediated cell signaling in hPMVEC. We speculate that the ErbB members identified in hPMVEC and the mechanism by which ErbB dimerizes represent potential novel therapeutic targets for pulmonary hypertensive disorders associated with hypoxia. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .