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Discoidin domain receptor 1 controls growth and adhesion of mesangial cells
Cyrile A Curat1, Wolfgang F Vogel
1Georg-Speyer-Haus, Institute for Biomedical Research, Frankfurt am Main, Germany.
Abstract:
Various types of collagen are known as modulators of mesangial cell proliferation. Here the function of the collagen-binding tyrosine kinase receptor discoidin domain receptor 1 (DDR1) in mesangial cells is investigated. The expression of DDR1 in the mouse kidney is confirmed by Northern analysis. In primary mesangial cells isolated from wild-type and DDR1-null mice, tyrosine phosphorylation in response to collagen-stimulation, adhesion to collagen, and cellular proliferation were measured. DDR1 phosphorylation was induced after overnight incubation of cells with type I collagen. Compared with wild-type cells, the adhesion of DDR1-null cells was drastically reduced. In contrast, DDR1-knockout cells showed significantly enhanced proliferation compared with wild-type cells. Both effects were largely independent of the collagen-binding alpha1/beta1 integrin function. This study found that the increased proliferation rate of DDR1-null cells is caused by a constitutive upregulation of p42/p44 and p38 mitogen-activated protein kinases (MAPK) activity. This is the first evidence indicating that DDR1 could be involved in the proliferative stage of renal disorders.
Insights
Discoidin domain receptor 1 (DDR1) regulates mesangial cell adhesion and proliferation. Loss of DDR1 enhances cell proliferation by upregulating MAPK activity, suggesting a role in kidney disorders.
Area of Science:
- Nephrology
- Cell Biology
- Molecular Biology
Background:
- Collagen modulates mesangial cell proliferation.
- Discoidin domain receptor 1 (DDR1) is a collagen-binding tyrosine kinase receptor.
Purpose of the Study:
- Investigate DDR1 function in mouse mesangial cells.
- Determine DDR1's role in collagen-mediated cellular responses.
Main Methods:
- Northern analysis to confirm DDR1 expression in mouse kidneys.
- Primary mesangial cell culture from wild-type and DDR1-null mice.
- Assays for tyrosine phosphorylation, collagen adhesion, and cell proliferation.
Main Results:
- DDR1 phosphorylation occurred upon type I collagen stimulation.
- DDR1-null cells exhibited reduced adhesion to collagen.
- DDR1-null cells showed significantly enhanced proliferation compared to wild-type cells.
- Enhanced proliferation in DDR1-null cells was linked to upregulated MAPK activity.
Conclusions:
- DDR1 negatively regulates mesangial cell proliferation.
- DDR1 signaling influences cell adhesion and proliferation independently of alpha1/beta1 integrins.
- DDR1 plays a role in the proliferative aspects of renal disorders.
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