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Isolation and characterization of a novel rat factor H-related protein that is up-regulated in glomeruli under complement attack.
Ren, Guohui; Doshi, Mona; Hack, Bradley K; Alexander, Jessy J; Quigg, Richard J.
Afiliación
  • Ren G; Section of Nephrology, Department of Medicine, the University of Chicago, Illinois 60637, USA.
J Biol Chem ; 277(50): 48351-8, 2002 Dec 13.
Article en En | MEDLINE | ID: mdl-12374811
The factor H family in humans is composed of seven distinct proteins, including factor H-related proteins (FHR) 1-5. All members contain tandemly arranged short consensus repeats (SCR) typical of the regulators of complement activation gene family. FHR-5 is unusual for this group of proteins, as it was initially identified as a component of immune deposits in glomerular diseases. During our cloning of the cDNA for rat factor H from glomerular epithelial cells (GEC), we identified an alternative 2729-bp cDNA transcript. The translated sequence encoded a protein containing 11 SCRs, most similar to SCRs 7-15 and 19-20 in native rat factor H, which is the same basic structure of human FHR-5. As such, this rat protein was termed FHR. Recombinant rat FHR produced in a eukaryotic expression system had a molecular mass of 78 kDa. In functional studies, recombinant FHR bound C3b and inhibited the complement alternative pathway in a dose-dependent fashion. Given the prominent expression of FHR-5 in human membranous nephropathy, a disease in which complement activation occurs in the vicinity of GEC, the expression of FHR in a rat model of this disease was evaluated. In both in vitro and in vivo models of complement activation on the GEC, FHR mRNA was up-regulated by a factor of 3-6-fold compared with controls in which complement could not be activated. Thus, we have identified a novel factor H family member in rats. This FHR protein is analogous to human FHR-5, both in structure and in potential involvement in glomerular immune complex diseases.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas del Sistema Complemento / Regulación hacia Arriba / Glomérulos Renales Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: J Biol Chem Año: 2002 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas del Sistema Complemento / Regulación hacia Arriba / Glomérulos Renales Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: J Biol Chem Año: 2002 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos