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
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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