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J Am Soc Nephrol 10:2495-2502, 1999
© 1999 American Society of Nephrology

Regulation of Rat Mesangial Cell Migration by Platelet-Derived Growth Factor, Angiotensin II, and Adrenomedullin

MASAKAZU KOHNO*, KENICHI YASUNARI*, MIEKO MINAMI*, HIROAKI KANO*, KENSAKU MAEDA*, ANIL K. MANDAL{dagger}, KEN INOKI{ddagger}, MASAKAZU HANEDA{ddagger} and JUNICHI YOSHIKAWA*

* First Department of Internal Medicine, Osaka City University Medical School, Osaka, Japan
{dagger} Division of Nephrology, Department of Medicine, Wright State University/VA Campus, Dayton, Ohio
{ddagger} The Third Department of Medicine, Shiga University of Medical Science, Shiga, Japan.

Correspondence to Dr. Masakazu Kohno, First Department of Internal Medicine, Osaka City University Medical School, 1-5-7 Asahi-machi, Abeno-ku, Osaka 545-8586, Japan. Phone: +81 6 6645 3801; Fax: +81 6 6645 3802.

Abstract. This study sought to determine whether platelet-derived growth factor (PDGF) and angiotensin II (AngII) stimulate migration of cultured rat glomerular mesangial cells. After finding that this was so, the effects of adrenomedullin (ADM) and cAMP-elevating agents on basal and stimulated mesangial cell migration were examined. Two isoforms of PDGF, AB and BB, stimulated migration in a concentration-dependent manner between 1 and 50 ng/ml, while the AA isoform lacked significant effect. AngII modestly but significantly stimulated migration in a concentration-dependent manner between 10-7 and 10-6 mol/L. Rat ADM significantly inhibited the PDGF BB- and AngII-stimulated migration in a concentration-dependent manner between 10-8 and 10-7 mol/L. Inhibition by rat ADM was accompanied by an increase in cellular cAMP. cAMP agonists or inducers such as 8-bromo cAMP, forskolin, and prostaglandin I2 also significantly reduced the stimulated migration. H 89, a protein kinase A (PKA) inhibitor, attenuated the inhibitory effect of ADM, and a calcitonin gene-related peptide (CGRP) receptor antagonist, human CGRP (8-37), abolished the inhibitory effects of rat ADM. These results suggest that PDGF AB and BB as well as AngII stimulate rat mesangial cell migration and that ADM can inhibit PDGF BB- and AngII-stimulated migration, at least in part through cAMP-dependent mechanisms likely to involve specific ADM receptors with which CGRP interacts. The adenylate cyclase/cAMP/PKA system may be involved in the migration-inhibitory effect of ADM in these cells.




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