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Isolation and Culture of Cells from the Nephrogenic Zone of the Embryonic Mouse Kidney
Published on: April 22, 2011
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Hypoxia-inducible factor 1α regulates branching morphogenesis during kidney development.
Kenji Tsuji1, Shinji Kitamura1, Hirofumi Makino1
1Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Biochemical and Biophysical Research Communications
|April 3, 2014
Summary
Hypoxia, a state of low oxygen, promotes kidney development by increasing ureteric bud branching. This process involves hypoxia-inducible factor (HIF) signaling and pathways like GDNF and FGF7.
Area of Science:
- Developmental Biology
- Renal Physiology
- Molecular Biology
Background:
- Kidneys undergo hypoxic conditions during development.
- Hypoxia-inducible factor (HIF) is a key mediator of cellular response to hypoxia.
- The precise role of HIF in kidney branching morphogenesis remains unclear.
Purpose of the Study:
- To investigate the role of HIF in regulating kidney development and branching morphogenesis.
- To determine if hypoxia influences ureteric bud branching and associated gene expression.
- To elucidate the signaling pathways involved in hypoxia-mediated kidney development.
Main Methods:
- Cultured embryonic day 13 rat kidneys under normoxic and hypoxic conditions.
- Assessed kidney morphology and gene expression.
- Utilized HIF-1α inhibitors (digoxin) and siRNA to block HIF activity.
- Examined apoptosis and gene expression in metanephric mesenchymal cells in vitro.
Main Results:
- Hypoxic conditions significantly increased ureteric bud branching in embryonic rat kidneys.
- Hypoxia upregulated GDNF and GFR-α1 mRNA levels.
- Inhibition of HIF-1α abolished hypoxia-induced branching and GDNF/GFR-α1 upregulation.
- Hypoxia reduced ureteric bud cell apoptosis and increased FGF7 mRNA in metanephric mesenchymal cells.
Conclusions:
- Hypoxia plays a crucial role in inducing branching morphogenesis during kidney development.
- HIF signaling is essential for mediating hypoxia's effects on kidney branching.
- Hypoxia may regulate kidney development through both GDNF/Ret and FGF signaling pathways.
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