このエントリーをはてなブックマークに追加
ID 53010
FullText URL
Author
Tsuji, Kenji
Abstract
The kidneys are exposed to hypoxic conditions during development. Hypoxia-inducible factor (HIF), an important mediator of the response to hypoxia, is believed to have an important role in development. However, the relationship between HIF and branching morphogenesis has not been elucidated clearly. In this study, we examined whether HIF regulates kidney development. We harvested kidneys from day 13 rat embryos (E13K5) and cultured the organs under normoxic (20% 02/5% CO2) or hypoxic (5% 02/5% CO2) conditions. We evaluated the kidneys based on morphology and gene expression. El3K5 cultured under hypoxic conditions had significantly more ureteric bud (UB) branching than the E13Ks cultured under normoxic conditions. In addition, the mRNA levels of GDNF and GDNF receptor (GFR-alpha l), increased under hypoxic conditions in E13K5. When we cultured E13Ks( with the HIF-1 alpha inhibitor digoxin or with siRNA targeting HIF-l alpha under hypoxic conditions, we did not observe increased UB branching. In addition, the expression of GDNF and GFR-alpha 1 was inhibited under hypoxic conditions when the kidneys were treated with siRNA targeting HIF-1 alpha. We also elucidated that hypoxia inhibited UB cell apoptosis and promoted the expression of FGF7 mRNA levels in metanephric mesenchymal (MM) cells in vitro. These findings suggest that hypoxic condition has important roles in inducing branching morphogenesis during kidney development. Hypoxia might mediate branching morphogenesis via not only GDNF/Ret but also FGF signaling pathway.
Keywords
HIF-I alpha
Kidney development
Hypoxia
Ureteric bud branching
Published Date
2014-04-25
Publication Title
Biochemical and Biophysical Research Communications
Volume
volume447
Issue
issue1
Publisher
Academic Press Inc Elsevier Science
Start Page
108
End Page
114
ISSN
0006-291X
NCID
AA00564395
Content Type
Journal Article
Related Url
http://ousar.lib.okayama-u.ac.jp/metadata/52966
language
英語
Copyright Holders
(c) 2014 Elsevier Inc. All rights reserved.
File Version
author
Refereed
True
DOI
Web of Sience KeyUT