title: Genomic analysis of a mouse model of immunoglobulin A nephropathy reveals an enhanced PDGF-EDG5 cascade.
abstract: The molecular mechanism of immunoglobulin A nephropathy (IgAN), the most common primary renal glomerular disease worldwide, is unknown. HIGA (high serum IgA) mouse is a valid model of IgAN showing almost all of the pathological features, including mesangial cell proliferation. Here we elucidate a pattern of gene expression associated with IgAN by analyzing the diseased kidneys on cDNA microarrays. In particular, we showed an enhanced expression of several genes regulating the cell cycle and proliferation, including growth factors and their receptors, as well as endothelial differentiation gene-5 (EDG5), a receptor for sphingosine 1-phosphate (SPP). One of the growth factors, platelet-derived growth factor (PDGF) induces a marked upregulation of EDG5 in proliferative mesangial cells, and promotes cell proliferation synergistically with SPP. The genomic approach allows us to identify families of genes involved in a process, and can indicate that enhanced PDGF-EDG5 signaling plays an important role in the progression of IgAN.
authors.affiliation: Department of Molecular, Cell Pharmacology, National Children's Medical Research Center, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Katsuma
authors.forename: S
authors.initials: S
authors.lastname: Shiojima
authors.forename: A
authors.initials: A
authors.lastname: Hirasawa
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
authors.forename: K
authors.initials: K
authors.lastname: Takagaki
authors.forename: M
authors.initials: M
authors.lastname: Murai
authors.forename: Y
authors.initials: Y
authors.lastname: Kaminishi
authors.forename: Y
authors.initials: Y
authors.lastname: Hada
authors.forename: M
authors.initials: M
authors.lastname: Koba
authors.forename: E
authors.initials: E
authors.lastname: Muso
authors.forename: S
authors.initials: S
authors.lastname: Miyawaki
authors.forename: T
authors.initials: T
authors.lastname: Ohgi
authors.forename: J
authors.initials: J
authors.lastname: Yano
authors.forename: G
authors.initials: G
authors.lastname: Tsujimoto
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism; D005922:Glomerulonephritis, IGA / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods / Q000706:statistics & numerical data*; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis / Q000235:genetics*; D051381:Rats; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid
chemical_list: D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid