Title: Reciprocal regulation of tissue-type and urokinase-type plasminogen activators in the differentiation of murine preadipocyte line 3T3-L1 and the hormonal regulation of fibrinolytic factors in the mature adipocytes
Authors: Seki, T ×
Miyasu, T
Noguchi, T
Hamasaki, A
Sasaki, R
Ozawa, Y
Okukita, K
Declerck, Paul
Ariga, T #
Issue Date: Oct-2001
Publisher: Wiley-liss
Series Title: Journal of cellular physiology vol:189 issue:1 pages:72-78
Abstract: Adipose tissue expresses a variety of genes including tumor necrosis factor alpha and type-1 plasminogen activator inhibitor (PAI-1); and these factors, produced by adipocytes, may be associated with the risk of coronary events in obesity. In this study, we characterized the production of fibrinolytic factors including tissue-type plasminogen activator (tPA), urokinase-type PA (uPA), and PAI-1 in the differentiation of preadipocytes, and examined the hormonal regulation of these fibrinolytic factors in mature adipocytes. Mouse 3T3-L1 preadipocytes were employed as a model of adipocytes. Adipocyte differentiation was induced by insulin, dexamethasone, and 3-isobutyl-1-methyl xanthine (IBMX). alpha -Glycerophosphate dehydrogenase (GPDH) activity and glucose transporter 4 (GLUT4) mRNA, indices for adipocyte maturation, were induced on Day 4, and gradually increased. GPDH activity reached its maximum level on Day 14. The level of tPA, a major PA in preadipocytes, dramatically decreased with differentiation. On the other hand, that of uPA reciprocally increased. PAI-1 production was also dramatically induced concomitant with differentiation. In mature adipocytes, uPA production was dominant (25 mug/ml/24 h vs. 0.8 mug/ml/24 h for tPA). Total PA activity in the mature adipocytes was reduced by insulin or clexamethasone, but not by glucagon. Insulin, IBMX, and clexamethasone significantly decreased both uPA and tPA production, and increased PAI-1 production. Glucagon had no effect on the production of these fibrinolytic factors. Our results reveal that uPA is one of the markers for the differentiation of 3T3-L1 cells and that insulin, IBMX, and clexamethasone are potent regulators of the fibrinolytic. activity in differentiated 3T3-L1 cells, reciprocally affecting PA and PAM levels in them. J. Cell. Physiol. 189: 72-78, 2001. (C) 2001 Wiley-Liss, Inc.
ISSN: 0021-9541
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory for Pharmaceutical Biology (-)
× corresponding author
# (joint) last author

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