Increased production of adrenomedullin in glomeruli from anti-glomerular basement membrane glomerulonephritis rats treated with methylprednisolone.
OBJECTIVE
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.


CONCLUSIONS
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.
Iwatsubo
Shuji
S
First Department of Internal Medicine, Miyazaki Medical College, University of Miyazaki, Miyazaki, Japan.
Fujimoto
Shouichi
S
Matsumoto
Michitaka
M
Sato
Yuji
Y
Hara
Seiichiro
S
Kitamura
Kazuo
K
Eto
Tanenao
T
D053607:Adrenomedullin; D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000188:drug therapy / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism*; D008775:Methylprednisolone / Q000627:therapeutic use*; D010455:Peptides / Q000378:metabolism*; D051381:Rats; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley
D010455:Peptides; D053607:Adrenomedullin; D008775:Methylprednisolone