Hedgehog signaling in neonatal and adult lung Journal Article
| Authors: | Liu, L.; Kugler, M. C.; Loomis, C. A.; Samdani, R.; Zhao, Z.; Chen, G. J.; Brandt, J. P.; Brownell, I.; Joyner, A. L.; Rom, W. N.; Munger, J. S. |
| Article Title: | Hedgehog signaling in neonatal and adult lung |
| Abstract: | Sonic Hedgehog (Shh) signaling is essential during embryonic lung development, but its role in postnatal lung development and adult lung are not known. Using Gli1nlacZ reporter mice to identify cells with activeHhsignaling,we found that Gli1nlacZ-positive mesenchymal cells are densely and diffusely present up to 2 weeks after birth and decline in number thereafter. In adult mice, Gli1nlacZ-positive cells are present around large airways and vessels and are sparse in alveolar septa. Hh-stimulated cells aremostlyfibroblasts;only10%of Gli1nlacZ-positive cells are smooth muscle cells, and most smooth muscle cells do not have activation of Hh signaling. To assess its functional relevance, we influenced Hh signaling in the developing postnatal lung and adult injured lung. Inhibition of Hh signaling during early postnatal lung development causes airspace enlargement without diminished alveolar septation. After bleomycin injury in the adult lung, there are abundant Gli1nlacZ-positive mesenchymal cells in fibrotic lesions and increased numbers of Gli1nlacZ-positive cells in preserved alveolar septa. Inhibition of Hh signaling with an antibody against all Hedgehog isoforms does not reduce bleomycin-induced fibrosis, but adenovirus-mediated overexpression of Shh increases collagen production in this model. Our data provide strong evidence that Hh signaling can regulate lung stromal cell function in two critical scenarios: normal development in postnatal lung and lung fibrosis in adult lung. Copyright © 2013 by the American Thoracic Society. |
| Keywords: | immunohistochemistry; signal transduction; controlled study; protein expression; genetics; nonhuman; protein localization; animal cell; mouse; animal; metabolism; animals; mice; allele; animal tissue; cell function; mesenchyme cell; smooth muscle fiber; sonic hedgehog protein; animal experiment; animal model; hedgehog proteins; alleles; age factors; drug effect; pathology; mice, inbred c57bl; age; c57bl mouse; collagen type 1; collagen type i; animal embryo; gene expression regulation; gene expression regulation, developmental; transcription factor gli2; chemically induced disorder; newborn; lung; kruppel like factor; kruppel-like transcription factors; beta galactosidase; fibroblast; fibroblasts; lung fibroblast; bleomycin; embryo, mammalian; cell count; animals, newborn; myofibroblast; lung fibrosis; pulmonary fibrosis; transcription factor gli1; protein patched 1; adenoviridae; postnatal development; adenovirus; lung injury; myofibroblasts; hedgehog; lung alveolus epithelium; lung development; alveolarization; gli protein, mouse |
| Journal Title: | American Journal of Respiratory Cell and Molecular Biology |
| Volume: | 48 |
| Issue: | 6 |
| ISSN: | 1044-1549 |
| Publisher: | American Thoracic Society |
| Date Published: | 2013-06-01 |
| Start Page: | 703 |
| End Page: | 710 |
| Language: | English |
| DOI: | 10.1165/rcmb.2012-0347OC |
| PUBMED: | 23371063 |
| PROVIDER: | scopus |
| PMCID: | PMC3727871 |
| DOI/URL: | |
| Notes: | --- - Cited By (since 1996):2 - "Export Date: 2 December 2013" - "CODEN: AJRBE" - "Source: Scopus" |
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