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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

Reciprocal regulation of tissue‐type and urokinase‐type plasminogen activators in the... Adipose tissue expresses a variety of genes including tumor necrosis factor α 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). α‐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 μg/ml/24 h vs. 0.8 μg/ml/24 h for tPA). Total PA activity in the mature adipocytes was reduced by insulin or dexamethasone, but not by glucagon. Insulin, IBMX, and dexamethasone 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 dexamethasone are potent regulators of the fibrinolytic activity in differentiated 3T3‐L1 cells, reciprocally affecting PA and PAI‐1 levels in them. © 2001 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Cellular Physiology Wiley

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

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References (53)

Publisher
Wiley
Copyright
Copyright © 2001 Wiley‐Liss, Inc.
ISSN
0021-9541
eISSN
1097-4652
DOI
10.1002/jcp.1140
pmid
11573206
Publisher site
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Abstract

Adipose tissue expresses a variety of genes including tumor necrosis factor α 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). α‐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 μg/ml/24 h vs. 0.8 μg/ml/24 h for tPA). Total PA activity in the mature adipocytes was reduced by insulin or dexamethasone, but not by glucagon. Insulin, IBMX, and dexamethasone 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 dexamethasone are potent regulators of the fibrinolytic activity in differentiated 3T3‐L1 cells, reciprocally affecting PA and PAI‐1 levels in them. © 2001 Wiley‐Liss, Inc.

Journal

Journal of Cellular Physiology – Wiley

Published: Oct 1, 2001

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