Expression and regulation of adrenomedullin in renal glomerular podocytes.
Adrenomedullin (AM) is postulated to exert organ-protective effects. It is expressed in the renal glomeruli, but its roles in the glomerular podocytes have been poorly elucidated. In the present study, we investigated the expression and regulation of AM in recently established conditionally immortalized mouse podocyte cell line in vitro and podocyte injury model in vivo. The cultured differentiated podocytes expressed AM mRNA and secreted measurable amount of AM. AM secretion from the podocytes was increased by H(2)O(2), hypoxia, puromycin aminonucleoside (PAN), albumin overload, and TNF-alpha. Real-time RT-PCR analysis revealed that AM mRNA expression in the podocytes was enhanced by PAN and TNF-alpha, both of which were suppressed by mitochondrial antioxidants. Furthermore, AM expression was upregulated in the glomerular podocytes of PAN nephrosis rats. These results indicated that AM expression in the podocytes was upregulated by stimuli or condition relevant to podocyte injury, suggesting its potential role in podocyte pathophysiology.
Hino
Masayo
M
Department of Nephrology and Endocrinology, University of Tokyo Graduate School of Medicine, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Nagase
Miki
M
Kaname
Shinya
S
Shibata
Shigeru
S
Nagase
Takashi
T
Oba
Shigeyoshi
S
Funaki
Masako
M
Kobayashi
Naoto
N
Kawachi
Hiroshi
H
Mundel
Peter
P
Fujita
Toshiro
T
D053607:Adrenomedullin; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D005786:Gene Expression Regulation / Q000187:drug effects; D007678:Kidney Glomerulus / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D010455:Peptides / Q000235:genetics*; D011692:Puromycin Aminonucleoside / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D017931:DNA Primers; D010455:Peptides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D053607:Adrenomedullin; D011692:Puromycin Aminonucleoside