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2013 ; 48
(6
): 703-10
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Hedgehog signaling in neonatal and adult lung
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Liu L
; Kugler MC
; Loomis CA
; Samdani R
; Zhao Z
; Chen GJ
; Brandt JP
; Brownell I
; Joyner AL
; Rom WN
; Munger JS
Am J Respir Cell Mol Biol
2013[Jun]; 48
(6
): 703-10
PMID23371063
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Sonic Hedgehog (Shh) signaling is essential during embryonic lung development,
but its role in postnatal lung development and adult lung are not known. Using
Gli1(nlacZ) reporter mice to identify cells with active Hh signaling, we found
that Gli1(nlacZ)-positive mesenchymal cells are densely and diffusely present up
to 2 weeks after birth and decline in number thereafter. In adult mice,
Gli1(nlacZ)-positive cells are present around large airways and vessels and are
sparse in alveolar septa. Hh-stimulated cells are mostly fibroblasts; only 10% of
Gli1(nlacZ)-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 Gli1(nlacZ)-positive mesenchymal
cells in fibrotic lesions and increased numbers of Gli1(nlacZ)-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.
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