title: Differential expression of type IV collagen isoforms in rat glomerular endothelial and mesangial cells.
abstract: Type IV collagen, which is encoded by six genetically distinct alpha-chains (alpha 1-alpha 6), is a major component of the kidney glomerulus. The alpha 1(IV) and alpha 2(IV) chains are present predominantly in the mesangial matrix, whereas the alpha 3(IV), alpha 4(IV), and alpha 5(IV) chains are localized almost exclusively to the glomerular basement membrane (GBM). Thickening of the GBM and expansion of the mesangial matrix are believed to contribute to the pathogenesis of diabetic nephropathy. In the present study, we evaluated the expression of alpha 1(IV), alpha 3(IV), and alpha 5(IV) chains in rat glomerular endothelial (GEndC) and mesangial cells (GMC). Under physiological concentrations of glucose (5 mM), alpha 1(IV) and alpha 5(IV) chains were detectable in GMCs, with an obvious absence of alpha 3(IV) chain. All three isoforms tested were present in GEndCs. At diabetic concentrations of glucose (25 mM), alpha 1(IV) was up-regulated in GMCs, whereas expression level of alpha 1(IV) remained unaltered in GEndCs. The alpha 3(IV) and alpha 5(IV) chains were up-regulated in GEndCs, but remained unchanged in GMCs under diabetic glucose concentrations (25 mM). Collectively, our results demonstrate that GMC might contribute to mesangial matrix expansion, mediated by alpha 1(IV) collagen, while GEndC might contribute to thickening of GBM, mediated by alpha 3(IV) collagen, in patients with diabetic nephropathy.
authors.affiliation: Program in Matrix Biology, Renal and Gastroenterology Divisions, Department of Medicine and the Liver Center, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Zeisberg
authors.forename: Mark B
authors.initials: MB
authors.lastname: Ericksen
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hamano
authors.forename: Eric G
authors.initials: EG
authors.lastname: Neilson
authors.forename: Fuad
authors.initials: F
authors.lastname: Ziyadeh
authors.forename: Raghu
authors.initials: R
authors.lastname: Kalluri
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D024141:Collagen Type IV / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000378:metabolism; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000166:cytology / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism*; D051381:Rats; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
chemical_list: D024141:Collagen Type IV; D020033:Protein Isoforms; D016212:Transforming Growth Factor beta; D005947:Glucose