Amino-terminal fragment (1-34) of parathyroid hormone-related protein inhibits migration and proliferation of cultured vascular smooth muscle cells.
We investigated the effects of amino-terminal fragment (1-34) of parathyroid hormone-related protein [PTHrP-(1-34)] on the migration and proliferation of vascular smooth muscle cells (VSMCs). Cultured VSMCs (5-9th passage) obtained from the aortas of male Wistar rats were used in this study. Migration of VSMCs was assessed using a modified Boyden's chamber. Proliferation of VSMCs was evaluated by measuring [3H]thymidine incorporation and counting cell numbers. PTHrP-(1-34) inhibited 10% fetal bovine serum (FBS)-induced increase in migration of VSMCs (61% of control at 1 micromol/l) in a concentration-dependent manner. PTHrP-(1-34) also inhibited 5% FBS-induced increase in [3H]thymidine incorporation (37% of control at 1 micromol/l) and cell number of VSMCs (33% of control at 1 micromol/l) in a concentration-dependent manner. Parathyroid hormone (PTH)-(1-34) inhibited the migration and DNA synthesis of VSMCs to a similar extent. PTHrP-(7-34), a PTH/PTHrP receptor antagonist, significantly inhibited these effects of PTHrP and PTH. PTHrP-(1-34) also inhibited platelet-derived growth factor-BB (5 ng/ml)-induced migration and DNA synthesis of VSMCs. These findings suggest that PTHrP-(1-34) inhibits the migration and proliferation of VSMCs through PTH/PTHrP receptors.
Ishikawa
M
M
Department of Geriatrics, Faculty of Medicine, University of Tokyo, Japan.
Akishita
M
M
Kozaki
K
K
Toba
K
K
Namiki
A
A
Yamaguchi
T
T
Orimo
H
H
Ouchi
Y
Y
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D006801:Humans; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D010281:Parathyroid Hormone / Q000494:pharmacology; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000494:pharmacology*; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000959:Antihypertensive Agents; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; C054296:parathyroid hormone-related protein (1-34)