Regulation of rat mesangial cell migration by platelet-derived growth factor, angiotensin II, and adrenomedullin.
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.
Kohno
M
M
First Department of Internal Medicine, Osaka City University Medical School, Japan.
Yasunari
K
K
Minami
M
M
Kano
H
H
Maeda
K
K
Mandal
A K
AK
Inoki
K
K
Haneda
M
M
Yoshikawa
J
J
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D053607:Adrenomedullin; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000077214:Becaplermin; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D013449:Sulfonamides
D004791:Enzyme Inhibitors; D007546:Isoquinolines; D010446:Peptide Fragments; D010455:Peptides; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D013449:Sulfonamides; C075278:platelet-derived growth factor A; C095477:platelet-derived growth factor AB; D000804:Angiotensin II; C058636:calcitonin gene-related peptide (8-37); D053607:Adrenomedullin; D000077214:Becaplermin; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D011464:Epoprostenol; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D015740:Calcitonin Gene-Related Peptide; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide