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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Publikationen des W. G. Kerckhoff-Instituts     Display Documents

ID: 428421.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Publikationen des W. G. Kerckhoff-Instituts
Spatiotemporal expression of flk-1 in pulmonary epithelial cells during lung development
Authors:Ahlbrecht, K.; Schmitz, J.; Seay, U.; Schwarz, C.; Mittnacht-Kraus, R.; Gaumann, A.; Haberberger, R. V.; Herold, S.; Breier, G.; Grimminger, F.; Seeger, W.; Voswinckel, R.
Date of Publication (YYYY-MM-DD):2008
Audience:Not Specified
Abstract / Description:Vascular endothelial growth factor-A (VEGF-A) responsive effects mediated via the receptors fetal liver kinase-1 (flk-1) and fms-like tyrosine kinase (flt-1), are key processes of pulmonary vascular development. Flk-1 has been shown to be involved in early embryonic lung epithelial to endothelial crosstalk and branching morphogenesis. Recent reports suggested a role of VEGF-A in lung epithelial cell function. Based on these observations, we hypothesize that epithelial flk-1 has a unique function in pulmonary development. Thus, the aim of this study is to elucidate spatiotemporal expression of flk-1 during lung development with respect to the epithelial system. Embryonic lungs were screened for flk-1 messenger RNA and protein at daily intervals, including postnatal stages. From Embryonic Day (ED) 12.5 through ED 15.5, flk-1 expression was restricted to the early vascular primitive network, while from ED 16.5 on flk-1 was detectable in the epithelial system and persisted there postnatally. At postnatal stages, flk-1 expression was increasingly restricted to individual cells in the alveolar septa. Isolation and in vitro cultivation of alveolar epithelial cells confirmed flk-1 expression and showed VEGF secretion into the supernatant. To our knowledge, this is the first murine study characterizing epithelial flk-1 expression at different stages throughout lung organogenesis until birth and at postnatal stages. To confirm epithelial flk-1 expression, we performed reporter gene analysis of the flk-1 promoter in vivo. Investigations on transgenic mouse strains, containing either a complete or incomplete flk-1 promoter driving expression of the lacZ reporter gene, suggested differential flk-1 regulation in endothelial and epithelial cells.
Free Keywords:Animals Animals, Newborn Cells, Cultured Endothelium, Vascular/metabolism Epithelial Cells/*metabolism Gene Expression Regulation, Developmental Lung/embryology/growth & development/*metabolism Mice Mice, Transgenic Pulmonary Alveoli/cytology/drug effects/metabolism RNA, Messenger/biosynthesis Respiratory Mucosa Vascular Endothelial Growth Factor A/physiology Vascular Endothelial Growth Factor Receptor-2/*biosynthesis/genetics
External Publication Status:published
Document Type:Other
Communicated by:N. N.
Affiliations:MPI für physiologische und klinische Forschung
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