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| Regulation of rat mesangial cell migration by platelet-derived growth factor, angiotensin II, and adrenomedullin |
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| Author(s): Kohno M, Yasunari K, Minami M, Kano H, Maeda K, Mandal AK, Inoki K, Haneda M, Yoshikawa J |
| Source: JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Volume: 10 Issue: 12 Pages: 2495-2502 Published: DEC 1999 |
| Times Cited: 49 References: 22 |
| 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 BE, 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 I-2 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 BE 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Kohno, M (reprint author), Osaka City Univ, Sch Med, Dept Internal Med 1, Abeno Ku, 1-5-7 Asahi Machi, Osaka 5458586, Japan |
Addresses:
1. Osaka City Univ, Sch Med, Dept Internal Med 1, Abeno Ku, Osaka 5458586, Japan
2. Wright State Univ, Dept Med,Div Nephrol, Dayton, OH 45435 USA
3. Shiga Univ Med Sci, Dept Med 3, Shiga, Japan |
| Publisher: LIPPINCOTT WILLIAMS & WILKINS, 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA |
| Subject Category: Urology & Nephrology |
| IDS Number: 259CH |
| ISSN: 1046-6673 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |