HB-EGF decelerates cell proliferation synergistically with TGFalpha in perinatal distal lung development.
Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of the EGF family of growth factors that is suggested to be involved in distal lung development. In HB-EGF null (HB(del/del)) newborns, a histopathologic analysis revealed abnormally thick saccular walls occurring from embryonic day 18.5 that reduced the terminal saccular space area. HB-EGF gene deletion resulted in a significant increase in cell proliferation, indicating that HB-EGF suppresses distal lung cell proliferation. Furthermore, an analysis of saccular morphology and proliferation in HB-EGF and transforming growth factor-alpha (TGFalpha) double-mutant newborns revealed that HB-EGF and TGFalpha function synergistically in this suppression. Finally, crosses between HB(del/del) mice and waved 2 mice, a hypomorphic EGF receptor (EGFR) mutant strain, suggest that HB-EGF and EGFR cooperate in this process. Thus, HB-EGF has a novel suppressive function that contributes to decelerating distal lung cell proliferation synergistically with TGFalpha through EGFR in perinatal distal lung development.
Minami
Seigo
S
Department of Cell Biology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Iwamoto
Ryo
R
Mekada
Eisuke
E
D000818:Animals; D000831:Animals, Newborn; D049109:Cell Proliferation; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D066257:Heparin-binding EGF-like Growth Factor; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D008168:Lung / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016211:Transforming Growth Factor alpha / Q000235:genetics* / Q000378:metabolism / Q000502:physiology
C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D016211:Transforming Growth Factor alpha; D066246:ErbB Receptors