PUBLICATION

Insulin-like growth factor-binding protein-1 (IGFBP-1) mediates hypoxia-induced embryonic growth and developmental retardation

Authors
Kajimura, S., Aida, K., and Duan, C.
ID
ZDB-PUB-050113-5
Date
2005
Source
Proceedings of the National Academy of Sciences of the United States of America   102(4): 1240-1245 (Journal)
Registered Authors
Duan, Cunming
Keywords
none
MeSH Terms
  • Animals
  • Cells, Cultured
  • Embryonic Development
  • Fetal Growth Retardation/etiology*
  • Hypoxia/complications*
  • Hypoxia/physiopathology
  • Insulin-Like Growth Factor Binding Protein 1/analysis
  • Insulin-Like Growth Factor Binding Protein 1/genetics
  • Insulin-Like Growth Factor Binding Protein 1/physiology*
  • Zebrafish
PubMed
15644436 Full text @ Proc. Natl. Acad. Sci. USA
Abstract
Although reduced fetal growth in response to hypoxia has been appreciated for decades, we have a poor understanding of the effects of hypoxia on embryonic development and the underlying cellular and molecular mechanisms. Here we show that hypoxia treatment not only resulted in embryonic growth retardation but also caused significant delay in developmental speed and the timing of morphogenesis in vital organs of zebrafish. Hypoxia strongly induced the expression of insulin-like growth factor (IGF)-binding protein (IGFBP)-1, a secreted protein that binds IGFs in extracellular environments. Hypoxia did not change the expression levels of IGFs, IGF receptors, or other IGFBPs. The hypothesis that elevated IGFBP-1 mediates hypoxia-induced embryonic growth retardation and developmental delay by binding to and inhibiting the activities of IGFs was tested by loss- and gain-of-function approaches. Knockdown of IGFBP-1 significantly alleviated the hypoxia-induced growth retardation and developmental delay. Overexpression of IGFBP-1 caused growth and developmental retardation under normoxia. Furthermore, reintroduction of IGFBP-1 to the IGFBP-1 knocked-down embryos restored the hypoxic effects on embryonic growth and development. When tested in vitro with cultured zebrafish embryonic cells, IGFBP-1 itself had no mitogenic activity, but it inhibited IGF-1- and IGF-2-stimulated cell proliferation. This inhibitory effect was abolished when IGF-1 or IGF-2 was added in molar excess, suggesting that IGFBP-1 inhibits embryonic growth and development by binding to and inhibiting the activities of IGFs. The induction of IGFBP-1 expression may be a conserved physiological mechanism to restrict the IGF-stimulated growth and developmental process under hypoxic stress.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping