The α-Isoform of Caveolin-1 Is a Marker of Vasculogenesis in Early Lung Development

Abstract

Caveolin-1 is a scaffolding protein component of caveolae, membrane invaginations involved in endocytosis, signal transduction, trans- and intracellular trafficking, and protein sorting. In adult lung, caveolae and caveolin-1 are present in alveolar endothelium and Type I epithelial cells but rarely in Type II cells. We have analyzed patterns of caveolin-1 expression during mouse lung development. Two caveolin-1 mRNAs, full-length and a 5' variant that will translate mainly into caveolin-1alpha and -beta isoforms, are detected by RT-PCR at embryonic day 12 (E12) and afterwards in the developing and adult lung. Immunostaining analysis, starting at E10, shows caveolin-1alpha localized in primitive blood vessels of the forming lung, in an overlapping pattern to the endothelial marker PECAM-1, and later in all blood vessels. Caveolin-1alpha is not detected in fetal or neonatal lung epithelium but is detected in adult epithelial Type I cells. Caveolin-1 was previously shown to be expressed in alveolar Type I cells. These data suggest that expression of caveolin-1 isoforms is differentially regulated in endothelial and epithelial cells during lung development. Caveolin-1alpha is an early marker for lung vasculogenesis, primarily expressed in developing blood vessels. When the lung is fully differentiated postnatally, caveolin-1alpha is also expressed in alveolar Type I cells.

Extensive vascularization of developing mouse ovaries revealed by caveolin‐1 expression

“…2A-F). These observations are consistent with reports of a high density of caveolae on endothelial cells (Scherer et al, 1995;Glienke et al, 2000), of caveolin-1 protein expression in vasculature of the fetal lung (Ramirez et al, 2002), and of more widespread Cav-1 mRNA expression in the developing cardiovascular system in mice (Fig. 1A and Bullejos et al, unpublished data).…”

Transcription of the Caveolin-1 Gene Is Differentially Regulated in Lung Type I Epithelial and Endothelial Cell Lines

“…Consistent with this hyperproliferative phenotype, embryonic fibroblasts derived from the null animals appear to have an increased rate of proliferation, which is partially reversed by re-expressing caveolin-1 protein from a viral expression vector (5). In intact animals loss of caveolin-1 leads to lung abnormalities at 2-4 months, about the same postnatal time point that caveolin-1␣ is first detectable by immunohistochemistry in type I cells in normal animals (4). The pulmonary phenotype appears to contribute to the shortened life span of the null animals although there are uncertainties about the actual cause of early death (8).…”

“…alveolar epithelial type I cells and alveolar capillary endothelial cells, reside within a short distance from each other and therefore share many environmental influences (4). Furthermore, targeted deletions of caveolin-1 in mice show mainly a pulmonary phenotype, pulmonary hypertension as well as hyperproliferative and fibrotic lung tissue (5)(6)(7).…”

“…Immunohistochemistry studies of embryonic, fetal, and adult mouse lung using an antibody that recognizes the caveolin-1␣ isoform show that caveolin-1␣ expression is present in developing endothelial cells but is not detectable in epithelial cells at the same developmental time points, suggesting differential regulation between the two cell types (4). No caveolin-1␣ expression is detectable in epithelial cells before birth.…”

“…No caveolin-1␣ expression is detectable in epithelial cells before birth. In the adult lung, caveolin-1␣ can be detected in both type I epithelial cells and endothelial cells but rarely in type II cells (4). Most interesting, in primary culture, alveolar type II cells growing on a plastic substratum acquire an alveolar type I phenotype as evidenced by an increase in many type I cell-specific proteins including caveolin-1.…”