このエントリーをはてなブックマークに追加
ID 53010
フルテキストURL
著者
Tsuji, Kenji Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
Kitamura, Shinji Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
Makino, Hirofumi Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
抄録
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.
キーワード
HIF-I alpha
Kidney development
Hypoxia
Ureteric bud branching
発行日
2014-04-25
出版物タイトル
Biochemical and Biophysical Research Communications
447巻
1号
出版者
Academic Press Inc Elsevier Science
開始ページ
108
終了ページ
114
ISSN
0006-291X
NCID
AA00564395
資料タイプ
学術雑誌論文
関連URL
http://ousar.lib.okayama-u.ac.jp/metadata/52966
言語
English
OAI-PMH Set
岡山大学
著作権者
(c) 2014 Elsevier Inc. All rights reserved.
論文のバージョン
author
査読
有り
DOI
Web of Sience KeyUT