Growth regulation of bovine retinal pericytes by transforming growth factor-beta2 and plasmin.
OBJECTIVE
Transforming growth factor -beta2 (TGF-beta2) is a predominant isoform of TGF-betas in the eye and plasmin is a peptidase with many functions. To better understand the pathogenesis of retinal microcirculation disorders, the effects of TGF-beta2 and plasmin on cultured bovine retinal pericytes were investigated.


METHODS
Exogenous TGF-beta2 or plasmin was added to some cultures, DNA synthesis during cell cycle progression was investigated using [(3)H]thymidine incorporation. Anti-TGF-beta2 antibody was added to neutralize the effects of TGF-beta2. TGF-beta2 in the culture medium was measured using enzyme-linked immunosorbent assay (ELISA).


RESULTS
Exogenous TGF-beta2 (10 pg to 100 ng/mL) suppressed DNA synthesis. Pericytes produced TGF-beta2. Anti-TGF-beta2 antibody neutralized TGF-beta2 and accelerated DNA synthesis, which shows that pericytes regulate their own cell cycle by action of the autocrine and/or paracrine system of TGF-beta2. Plasmin (0.2 to 0.5 U/mL) accelerated DNA synthesis in a dose-dependent manner, while addition of aprotinin, a protease inhibitor, counteracted this effect of plasmin. The concentration of TGF-beta2 in the culture medium decreased with the addition of plasmin. Simultaneous addition of both plasmin and anti-TGF-beta2 antibody accelerated DNA synthesis. High and low glucose concentrations of the culture medium did not affect DNA synthesis.


CONCLUSIONS
Our results suggest that TGF-beta2 and plasmin respectively decrease and increase DNA synthesis. In a retinal microcirculation disorder, they may play competitive roles in the cell cycle of pericytes.
Katsura
M K
MK
Department of Ophthalmology, Hiroshima University School of Medicine, Japan.
Mishima
H K
HK
Minamoto
A
A
Ishibashi
F
F
Yamashita
H
H
D000818:Animals; D002417:Cattle; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D003470:Culture Media / Q000494:pharmacology; D017077:Culture Media, Conditioned / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005341:Fibrinolysin / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D020286:Pericytes / Q000166:cytology / Q000187:drug effects*; D012160:Retina / Q000166:cytology / Q000187:drug effects*; D013936:Thymidine / Q000493:pharmacokinetics; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology*; D014316:Tritium
D003470:Culture Media; D017077:Culture Media, Conditioned; D016212:Transforming Growth Factor beta; D014316:Tritium; D005341:Fibrinolysin; D005947:Glucose; D013936:Thymidine