Premium
Loss of BMPR2 Confers Proliferative Advantage on Pulmonary Artery Endothelial Cells by Decreasing Dependence on Growth Suppressor Merlin
Author(s) -
Josephs Caleb A.,
Ceballos Rhandy,
Vasauskas Audrey A.,
Morrow Rebekah L.,
Morrow Kyle Adam
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.917.7
Subject(s) - gene knockdown , cancer research , biology , cell growth , merlin (protein) , bmpr2 , endothelial stem cell , pathology , microbiology and biotechnology , medicine , cell culture , cancer , bone morphogenetic protein , in vitro , suppressor , genetics , gene
Pulmonary artery endothelial cells (PAECs) exhibit an abrogated proliferative phenotype when compared to pulmonary microvascular endothelial cells (PMVECs). Pulmonary arterial hypertension (PAH) is a disease characterized by occlusive lesions in the pulmonary vasculature, potentially due to a heightened proliferative capacity of pulmonary endothelial cells. The cytoskeletal linker protein Merlin functions to suppress proliferation in a contact‐dependent manner in a variety of tissues. Loss of Merlin contributes to certain types of lung cancer. Mutations in the bone morphogenic protein receptor 2 (BMPR2) are frequently seen in patients with PAH, and reduced BMPR2 is implicated in a cancer‐like, highly proliferative phenotype of pulmonary microvascular endothelial cells. However, the role of BMPR2 in pulmonary artery endothelial cell proliferation remains unclear. Here, we test the hypothesis that a reduction of BMPR2 confers a growth advantage on PAECs by altering Merlin status. Wild‐type PAECs and PMVECs were grown to sub‐confluence (~80%) or full confluence, cell lysates were harvested, and Merlin levels were assessed. As Merlin functions to suppress growth in a contact‐dependent manner, as expected, PAECs possessed higher levels of Merlin at full confluence than at sub‐confluence. Interestingly, Merlin protein was not detected at sub‐confluence or full confluence in PMVECs. Wild‐type PAECs and PAECs with reduced BMPR2 (BMPR2 knockdown) were assessed for proliferative capacity by traditional and image‐based growth curve analysis. BMPR2 knockdown cells showed increased proliferative capacity when compared with wild‐type PAECs. BMPR2 knockdown and wild‐type PAECs were grown to sub‐confluence and full confluence, cell lysates were harvested, and Merlin levels were assessed. When compared to wild‐type PAECS, BMPR2 knockdown cells appeared to increase Merlin levels to a lesser extent as confluence increased. Thus, we provide evidence of a link between reduced BMPR2 in PAECs contributing to enhanced proliferative capacity, potentially due to a decreased dependence on the growth suppressor Merlin. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .