title: Activation of type II cells into regenerative stem cell antigen-1(+) cells during alveolar repair.
abstract: The alveolar epithelium is composed of two cell types: type I cells comprise 95% of the gas exchange surface area, whereas type II cells secrete surfactant, while retaining the ability to convert into type I cells to induce alveolar repair. Using lineage-tracing analyses in the mouse model of Pseudomonas aeruginosa-induced lung injury, we identified a population of stem cell antigen (Sca)-1-expressing type II cells with progenitor cell properties that mediate alveolar repair. These cells were shown to be distinct from previously reported Sca-1-expressing bronchioalveolar stem cells. Microarray and Wnt reporter studies showed that surfactant protein (Sp)-C(+)Sca-1(+) cells expressed Wnt signaling pathway genes, and inhibiting Wnt/β-catenin signaling prevented the regenerative function of Sp-C(+)Sca-1(+) cells in vitro. Thus, P. aeruginosa-mediated lung injury induces the generation of a Sca-1(+) subset of type II cells. The progenitor phenotype of the Sp-C(+)Sca-1(+) cells that mediates alveolar epithelial repair might involve Wnt signaling.
authors.affiliation: Departments of 1 Pharmacology.
authors.forename: Yuru
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Departments of 1 Pharmacology.
authors.forename: Varsha Suresh
authors.initials: VS
authors.lastname: Kumar
authors.affiliation: 2 Pediatrics, and.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Departments of 1 Pharmacology.|3 Medicine, University of Illinois College of Medicine, Chicago, Illinois.
authors.forename: Jalees
authors.initials: J
authors.lastname: Rehman
authors.affiliation: Departments of 1 Pharmacology.
authors.forename: Asrar B
authors.initials: AB
authors.lastname: Malik
mesh_terms: D056809:Alveolar Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D018410:Pneumonia, Bacterial / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011552:Pseudomonas Infections / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011550:Pseudomonas aeruginosa; D037721:Pulmonary Surfactant-Associated Protein C; D020545:Respiratory Mucosa / Q000378:metabolism / Q000473:pathology; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D060449:Wnt Signaling Pathway / Q000235:genetics
chemical_list: D000950:Antigens, Ly; D036341:Intercellular Signaling Peptides and Proteins; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D010455:Peptides; D037721:Pulmonary Surfactant-Associated Protein C; C489680:Sftpc protein, mouse
keywords: lung; progenitor cell; repair; stem cell antigen-1; type II cell