title: Temporal changes in expression of FoxA1 and Wnt7A in isolated adult human alveolar epithelial cells enhanced by heparin.
abstract: Pre- and postnatal developmental studies of the lung have provided compelling evidence demonstrating multiple factors that orchestrate alveolar epithelial cell differentiation. The extent to which reactivation of certain developmental pathways in the adult might influence the course of differentiation of alveolar type 2 cells (AT2) into AT1 cells is not known. In this study, we examined selected members of the forkhead (Fox) family of transcription factors and the Wnt (wingless) family of signaling proteins for expression during human alveolar cell differentiation in vitro and determined their potential responses to sulfated components of extracellular matrix (ECM), like those shed from cell surfaces or found in basement membrane and modeled by heparin. Isolated adult human AT2 cells cultured over a 9-day period were used to define the temporal profile of expression of targeted factors during spontaneous differentiation to AT1-like cells. FoxA1 protein was upregulated at early to intermediate time points, where it was strongly elevated by heparin. Gene expression of wnt7A increased dramatically beginning on day 3 and was enhanced even further on days 7 and 9 by heparin, whereas protein expression appeared at days 7 and 9. These temporal changes of expression suggest that sulfated ECMs may act to enhance the increase in FoxA1 at the critical juncture when AT2 cells commence the differentiation process to AT1 cells, in addition to enhancing the increase in wnt7A when the AT1 cell phenotype stabilizes. Collectively, these factors may act to modulate differentiation in the adult human pulmonary alveolus.
authors.affiliation: Department of Molecular Biomedical Sciences, Center for Comparative Medicine and Translational Research, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.
authors.forename: K B C
authors.initials: KB
authors.lastname: Apparao
authors.forename: Donna R
authors.initials: DR
authors.lastname: Newman
authors.forename: Huiying
authors.initials: H
authors.lastname: Zhang
authors.forename: Jody
authors.initials: J
authors.lastname: Khosla
authors.forename: Scott H
authors.initials: SH
authors.lastname: Randell
authors.forename: Philip L
authors.initials: PL
authors.lastname: Sannes
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002469:Cell Separation; D002478:Cells, Cultured; D006493:Heparin / Q000502:physiology*; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D051153:Wnt Proteins / Q000096:biosynthesis* / Q000235:genetics; D051176:beta Catenin / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000925:Anticoagulants; D015415:Biomarkers; C496499:FOXA1 protein, human; D051541:Hepatocyte Nuclear Factor 3-alpha; C092778:WNT7A protein, human; D051153:Wnt Proteins; D051176:beta Catenin; D006493:Heparin