title: Lipopolysaccharide-induced injury is more pronounced in fetal transgenic ErbB4-deleted lungs.
abstract: Pulmonary ErbB4 deletion leads to a delay in fetal lung development, alveolar simplification, and lung function disturbances in adult mice. We generated a model of intrauterine infection in ErbB4 transgenic mice to study the additive effects of antenatal LPS administration and ErbB4 deletion during fetal lung development. Pregnant mice were treated intra-amniotically with an LPS dose of 4 μg at E17 of gestation. Lungs were analyzed 24 h later. A significant influx of inflammatory cells was seen in all LPS-treated lungs. In heterozygote control lungs, LPS treatment resulted in a delay of lung morphogenesis characterized by a significant increase in the fraction of mesenchyme, a decrease in gas exchange area, and disorganization of elastic fibers. Surfactant protein (Sftp)b and Sftpc were upregulated, but mRNA of Sftpb and Sftpc was downregulated compared with non-LPS-treated controls. The mRNA of Sftpa1 and Sftpd was upregulated. In ErbB4-deleted lungs, the LPS effects were more pronounced, resulting in a further delay in morphological development, a more pronounced inflammation in the parenchyma, and a significant higher increase in all Sftp. The effect on Sftpb and Sftpc mRNA was somewhat different, resulting in a significant increase. These results imply a major role of ErbB4 in LPS-induced signaling in structural and functional lung development.
authors: Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.
authors: Andreas
authors: A
authors: Schmiedl
authors: Jan
authors: J
authors: Behrens
authors: Katja
authors: K
authors: Zscheppang
authors: Erkhembulgan
authors: E
authors: Purevdorj
authors: Dietlinde
authors: D
authors: von Mayersbach
authors: Andrea
authors: A
authors: Liese
authors: Christiane E L
authors: CE
authors: Dammann
mesh_terms: D056809:Alveolar Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D004547:Elastic Tissue; D066246:ErbB Receptors / Q000172:deficiency* / Q000235:genetics; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D007249:Inflammation / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides / Q000009:adverse effects / Q000494:pharmacology*; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D037721:Pulmonary Surfactant-Associated Protein C; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D066247:Receptor, ErbB-4; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*; D014599:Uterus
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D010455:Peptides; D020033:Protein Isoforms; D037721:Pulmonary Surfactant-Associated Protein C; D012333:RNA, Messenger; C489680:Sftpc protein, mouse; D066246:ErbB Receptors; C587690:Erbb4 protein, mouse; D066247:Receptor, ErbB-4