Discoidin Domain Receptor 1 Controls Growth and Adhesion of Mesangial Cells

Abstract

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 α1/β1 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.