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HB‐EGF decelerates cell proliferation synergistically with TGFα in perinatal distal lung development
Author(s) -
Minami Seigo,
Iwamoto Ryo,
Mekada Eisuke
Publication year - 2008
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.21398
Subject(s) - epidermal growth factor , biology , heparin binding egf like growth factor , epidermal growth factor receptor , tgf alpha , transforming growth factor , cell growth , growth factor , lung , endocrinology , medicine , receptor , microbiology and biotechnology , cancer research , biochemistry
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‐α (TGFα) double‐mutant newborns revealed that HB‐EGF and TGFα 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 TGFα through EGFR in perinatal distal lung development. Developmental Dynamics 237:247–258, 2008. © 2007 Wiley‐Liss, Inc.