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Updated: Jul 31, 2026
08:06
Isolation and Culture of Cells from the Nephrogenic Zone of the Embryonic Mouse Kidney
Published on: April 22, 2011
Differential MAPK pathways utilized for HGF- and EGF-dependent renal epithelial morphogenesis.
A Karihaloo1, D A O'Rourke, C Nickel
1School of Medicine, Yale University, New Haven, Connecticut 06520, USA. anil.karihaloo@yale.edu
The Journal of Biological Chemistry
|December 29, 2000
Summary
Inner medullary collecting duct cells use distinct signaling pathways for growth. Hepatocyte growth factor (HGF) relies on ERK1/2, while epidermal growth factor (EGF) utilizes ERK5 for branching tubulogenesis.
Area of Science:
- Cell Biology
- Renal Physiology
- Molecular Signaling
Background:
- Inner medullary collecting duct (IMCD) cells exhibit in vitro branching tubulogenesis in response to hepatocyte growth factor (HGF) and epidermal growth factor (EGF).
- Unlike many renal epithelial cells, IMCD cells respond to both HGF and EGF, suggesting independent signaling pathways for these receptors during morphogenesis.
Purpose of the Study:
- To compare the specific signaling pathways utilized by mIMCD-3 cells for morphogenesis induced by EGF and HGF.
- To elucidate the roles of mitogen-activated protein kinase (MAPK) pathways, specifically ERK1/2 and ERK5, in HGF- and EGF-mediated cellular responses.
Main Methods:
- Utilized specific inhibitors of the mitogen-activated protein kinase kinase (MKK1) pathway, including PD98059 and U0126, to assess their impact on cell migration and branching morphogenesis.
- Investigated the activation of extracellular-regulated kinase 5 (ERK5) in response to EGF and HGF.
- Employed dominant-negative ERK5 (dnBMK1) to further delineate the role of ERK5 in EGF- and HGF-dependent processes.
Main Results:
- Inhibition of MKK1 with PD98059 partially inhibited EGF-induced motility but significantly inhibited HGF-induced migration and branching morphogenesis.
- EGF stimulation led to ERK5 activation, which was only partially inhibited by PD98059.
- The MKK inhibitor U0126 markedly inhibited both ERK1/2 and ERK5 activation, completely blocking HGF- and EGF-dependent migration and branching.
- Dominant-negative ERK5 specifically inhibited EGF-dependent branching but not HGF-dependent branching.
Conclusions:
- The ERK1/ERK2 signaling pathway is critical for HGF-induced cell motility and morphogenesis in mIMCD-3 cells.
- ERK5 signaling is essential for EGF-dependent morphogenesis in these cells.
- These findings highlight distinct molecular mechanisms governing renal epithelial cell morphogenesis mediated by different growth factor receptors.
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