title: Glomerulonephritis-induced changes in kidney gene expression in rats.
abstract: We investigated a glomerulonephritis (GN) model in rats induced by nephrotoxic serum (NTS) which contains antibodies against the glomerular basement membrane (GBM). The anti-GBM GN model in rats is widely used since its biochemical and histopathological characteristics are similar to crescentic nephritis and Goodpasture's disease in humans (Pusey, 2003[2]). Male Wistar Kyoto (WKY) and Sprague-Dawley (SD) rats were dosed once with 1, 2.5 and 5 ml/kg nephrotoxic serum (NTS) or 1.5 and 5 ml/kg NTS, respectively. GN and tubular damage were observed histopathologically in all treated rats after 14 days. To obtain insight into molecular processes during GN pathogenesis, mRNA expression was investigated in WKY and SD kidneys using Affymetrix's GeneChip Rat genome 230_2.0 arrays (GSE64265). The immunopathological processes during GN are still not fully understood and likely involve both innate and adaptive immunity. In the present study, several hundred mRNAs were found deregulated, which functionally were mostly associated with inflammation and regeneration. The β-chain of the major histocompatibility complex class II RT1.B (Rt1-Bb) and complement component 6 (C6) were identified as two mRNAs differentially expressed between WKY and SD rat strains which could be related to known different susceptibilities to NTS of different rat strains; both were increased in WKY and decreased in SD rats (Pavkovic et al., 2015 [1]). Increased Rt1-Bb expression in WKY rats could indicate a stronger and more persistent cellular reaction of the adaptive immune system in this strain, in line with findings indicating adaptive immune reactions during GN. The complement cascade is also known to be essential for GN development, especially terminal cascade products like C6.
authors.affiliation: Investigational Toxicology, GDD-GED-Toxicology, Bayer Pharma AG, 42096 Wuppertal, Germany ; Laboratory of Systems Pharmacology, Harvard Program in Therapeutic Sciences, Harvard Medical School, 02115 Boston, MA, United States.
authors.forename: Mira
authors.initials: M
authors.lastname: Pavkovic
authors.affiliation: Investigational Toxicology, GDD-GED-Toxicology, Bayer Pharma AG, 42096 Wuppertal, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Riefke
authors.affiliation: Pathology, GDD-GED-Toxicology, Bayer Pharma AG, 13353 Berlin, Germany.
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Frisk
authors.affiliation: Indication Expansion, GDD-GTRG-Cross Indication Platform, Bayer Pharma AG, 13353 Berlin, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Gröticke
authors.affiliation: Investigational Toxicology, GDD-GED-Toxicology, Bayer Pharma AG, 42096 Wuppertal, Germany.
authors.forename: Heidrun
authors.initials: H
authors.lastname: Ellinger-Ziegelbauer
keywords: Expression profiling; Glomerulonephritis; Rat strain-dependence