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Publication : Discoidin domain receptor 1 controls growth and adhesion of mesangial cells.

First Author  Curat CA Year  2002
Journal  J Am Soc Nephrol Volume  13
Issue  11 Pages  2648-56
PubMed ID  12397034 Mgi Jnum  J:103387
Mgi Id  MGI:3609309 Doi  10.1097/01.asn.0000032419.13208.0c
Citation  Curat CA, et al. (2002) Discoidin domain receptor 1 controls growth and adhesion of mesangial cells. J Am Soc Nephrol 13(11):2648-56
abstractText  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.
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