Distinct roles for IκB kinases alpha and beta in regulating pulmonary endothelial angiogenic function during late lung development
Autor: | Cristina M. Alvira, Min Liu, Shailaja P. Rao, Andrew Oman, Lihua Ying, Katherine R. Concepcion, Cristiana Iosef, Westin K. Chan |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Angiogenesis nuclear factor kappa‐B Organogenesis Primary Cell Culture Regulator Alpha (ethology) Neovascularization Physiologic Vascular Cell Adhesion Molecule-1 Apoptosis 03 medical and health sciences angiogenesis Mice 0302 clinical medicine Cell Movement medicine Cell Adhesion Gene silencing Animals RNA Small Interfering Lung lung development Cell Proliferation Kinase Microarray analysis techniques Cell adhesion molecule Chemistry NF-kappa B Endothelial Cells Gene Expression Regulation Developmental Cell Biology Original Articles 3. Good health Cell biology I-kappa B Kinase alveolarization Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Animals Newborn 030220 oncology & carcinogenesis Molecular Medicine Original Article Signal Transduction |
Zdroj: | Journal of Cellular and Molecular Medicine |
ISSN: | 1582-4934 1582-1838 |
Popis: | Pulmonary angiogenesis is essential for alveolarization, the final stage of lung development that markedly increases gas exchange surface area. We recently demonstrated that activation of the nuclear factor kappa‐B (NFκB) pathway promotes pulmonary angiogenesis during alveolarization. However, the mechanisms activating NFκB in the pulmonary endothelium, and its downstream targets are not known. In this study, we sought to delineate the specific roles for the NFκB activating kinases, IKKα and IKKβ, in promoting developmental pulmonary angiogenesis. Microarray analysis of primary pulmonary endothelial cells (PECs) after silencing IKKα or IKKβ demonstrated that the 2 kinases regulate unique panels of genes, with few shared targets. Although silencing IKKα induced mild impairments in angiogenic function, silencing IKKβ induced more severe angiogenic defects and decreased vascular cell adhesion molecule expression, an IKKβ regulated target essential for both PEC adhesion and migration. Taken together, these data show that IKKα and IKKβ regulate unique genes in PEC, resulting in differential effects on angiogenesis upon inhibition, and identify IKKβ as the predominant regulator of pulmonary angiogenesis during alveolarization. These data suggest that therapeutic strategies to specifically enhance IKKβ activity in the pulmonary endothelium may hold promise to enhance lung growth in diseases marked by altered alveolarization. |
Databáze: | OpenAIRE |
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