Increased Production of Adrenomedullin in Glomeruli from Anti-Glomerular Basement Membrane Glomerulonephritis Rats Treated with Methylprednisolone

Abstract

Background/Aims: Adrenomedullin (AM) has anti-proliferative and apoptotic effects on mesangial cells (MCs). Both effects play an important role in the progression of glomerulonephritis (GN). Glucocorticoids are widely used for the treatment of GN; however, the relationship between AM regulation in MCs or glomeruli and glucocorticoid treatment has not been clarified. Methods: Using the cultured rat MCs, AM secretion induced by methylprednisolone (m-PSL), and MC proliferation and apoptosis caused by AM were examined. In addition, the role of AM receptor antagonist, AM(22-52), was also investigated. Then, we made an anti-glomerular basement membrane (GBM) GN rat model and compared the AM expression and production in each glomeruli obtained from the control or m-PSL-treated anti-GBM GN rats. Results: In the cultured rat MCs, AM secretion was increased by m-PSL. MC proliferation was inhibited, while MC apoptosis was increased by AM. MC apoptosis was inhibited by the addition of AM(22-52). M-PSL therapy ameliorated the progression of anti-GBM GN rats. AM expression and production were increased in the glomeruli from m-PSL-treated rats compared to the controls. Conclusion: Considering the anti-proliferative and apoptotic effects of AM on MCs, increased AM in the glomeruli might participate in the improvement of glomerular lesions in anti-GBM GN rats treated with m-PSL.

Urinary podocyte and TGF-β1 mRNA as markers for disease activity and progression in anti-glomerular basement membrane nephritis

“…Rabbit anti-rat GBM serum [nephrotoxic serum (NTS)] was prepared as described previously [43,44]. The rat model of anti-GBM nephritis was induced in male Wistar-Kyoto rats that were 5 weeks old and weighed approximately 100 g (Charles River Breeding, Yokohama, Japan) with an intravenous injection of NTS (0.3 mL/100 g body weight).…”

“…A progressive model of anti-GBM nephritis using male Wistar-Kyoto rats was initiated by intravenous injection of rabbit anti-rat GBM serum (NTS) as previously described [43,44]. Figure 1A shows immunofluorescent anti-rabbit IgG staining, with no immunostaining seen in the glomerulus at day 0 (before NTS injection).…”