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Thimraj, T.A.* ; Birru, R.L.* ; Mitra, A.* ; Schulz, H. ; Leikauf, G.D.* ; Ganguly, K.*

Homeobox, Wnt, and fibroblast growth factor signaling is augmented during alveogenesis in mice lacking superoxide dismutase 3, extracellular.

Lung 195, 263-270 (2017)
Postprint Forschungsdaten DOI PMC
Open Access Green
Superoxide dismutase 3, extracellular (SOD3) polymorphisms have been implicated in reduced pulmonary function development and altered risk for chronic obstructive pulmonary disease. We previously reported that gene-targeted Sod3−/− mice have impaired lung function and human SOD3 variants are associated with reduced pulmonary function in children. Reduced lung SOD3 levels were reported in mice with lower lung function with the greatest difference occurring during alveogenesis phase [postnatal (P) days 14–28]. Interactions between homeobox (HOX), wingless-type MMTV integration site member (WNT), and fibroblast growth factor (FGF) signaling govern complex developmental processes in several organs. A subset of HOX family members, HOXA5 and HOXB5, is expressed in the developing lung. Therefore, in this study we assessed the transcript expression of these family members and their downstream targets in Sod3−/− mice during alveogenesis (P14). In the lung of Sod3−/− mice, Hoxa5 and Hoxb5 increased. These transcription factors regulate WNT gene expression and were accompanied by increases in their downstream targets Wnt2 and Wnt5A, canonical and noncanonical WNT members, respectively. The WNT signaling target, lymphoid enhancer binding factor 1 (Lef1), also increased along with its downstream targets Fgf2, Fgf7, and Fgf10 in the lungs of Sod3−/− mice. Due to limited knowledge on the role of FGF2 in lung development, we further examined FGF2 protein and found increased levels in the bronchial and alveolar type II epithelial cells of Sod3−/− mice compared to age-matched controls. Thus, our findings suggest that deficient management of extracellular superoxide can lead to altered lung developmental signaling during alveogenesis in mice.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Fgf ; Lung Development ; Oxidative Stress ; Superoxide ; Wnt; Obstructive-pulmonary-disease; Lung Epithelial-cells; Oxidative Fragmentation; Branching Morphogenesis; Rat Lung; Expression; Protects; Pathway; Progenitors; Emphysema
ISSN (print) / ISBN 0341-2040
e-ISSN 1432-1750
Zeitschrift Lung
Quellenangaben Band: 195, Heft: 2, Seiten: 263-270 Artikelnummer: , Supplement: ,
Verlag Springer
Verlagsort New York, NY
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)