Requirement for transglutaminase in the activation of latent transforming growth factor-beta in bovine endothelial cells.
A hitherto unknown function for transglutaminase (TGase; R-glutaminyl-peptide: amine gamma-glutamyltransferase, EC 2.3.2.13) was found in the conversion of latent transforming growth factor-beta (LTGF-beta) to active TGF-beta by bovine aortic endothelial cells (BAECs). The cell-associated, plasmin-mediated activation of LTGF-beta to TGF-beta induced either by treatment of BAECs with retinoids or by cocultures of BAECs and bovine smooth muscle cells (BSMCs) was blocked by seven different inhibitors of TGase as well as a neutralizing antibody to bovine endothelial cell type II TGase. Control experiments indicated that TGase inhibitors and/or a neutralizing antibody to TGase did not interfere with the direct action of TGF-beta, the release of LTGF-beta from cells, or the activation of LTGF-beta by plasmin or by transient acidification. After treatment with retinoids, BAECs expressed increased levels of TGase coordinate with the generation of TGF-beta, whereas BSMCs and bovine embryonic skin fibroblasts, which did not activate LTGF-beta after treatment with retinoids, did not. Furthermore, both TGase inhibitors and a neutralizing antibody to TGase potentiated the effect of retinol in enhancing plasminogen activator (PA) levels in cultures of BAECs by suppressing the TGF-beta-mediated enhancement of PA inhibitor-1 (PAI-1) expression. These results indicate that type II TGase is a component required for cell surface, plasmin-mediated LTGF-beta activation process and that increased expression of TGase accompanies retinoid-induced activation of LTGF-beta.
Kojima
S
S
Department of Cell Biology, New York University Medical School, NY.
Nara
K
K
Rifkin
D B
DB
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects; D001414:Bacitracin / Q000494:pharmacology; D001711:Biotransformation / Q000187:drug effects; D002417:Cattle; D002478:Cells, Cultured / Q000187:drug effects; D003538:Cystamine / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology; D005341:Fibrinolysin; D010960:Plasminogen Activators; D016212:Transforming Growth Factor beta / Q000187:drug effects / Q000378:metabolism*; D011503:Transglutaminases / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014801:Vitamin A / Q000494:pharmacology
D000906:Antibodies; D016212:Transforming Growth Factor beta; D014801:Vitamin A; D001414:Bacitracin; D011503:Transglutaminases; D010960:Plasminogen Activators; D005341:Fibrinolysin; D003538:Cystamine