No functional role of plasminogen activator inhibitor-1 in murine adipogenesis or adipocyte differentiation.
OBJECTIVE
To substantiate a potential role of plasminogen activator inhibitor-1 (PAI-1) in adipogenesis, we have studied its effects on in vitro adipocyte differentiation and on in vivo adipose tissue formation.


RESULTS
Our in vitro data do not support a functional role of PAI-1, as substantiated by our findings that: (i) inhibition of PAI-1 with a neutralizing antibody did not affect differentiation of 3T3-F442A preadipocytes; (ii) overexpression of murine PAI-1 in 3T3-F442A cells had no effect on differentiation; and (iii) differentiation of PAI-1-deficient murine embryonic fibroblasts into mature adipocytes was comparable to wild-type (WT) cells. Furthermore, our in vivo studies did not reveal an important role for PAI-1, as suggested by our findings that: (i) de novo fat pad formation in NUDE mice following injection of 3T3-F442A cells was not affected by a PAI-1 neutralizing antibody; and (ii) adipose tissue formation following combined injection of Matrigel and basic fibroblast growth factor was comparable in WT and in PAI-1 deficient mice.


CONCLUSIONS
Taken together, these in vitro and in vivo studies in murine model systems do not support an important functional role of PAI-1 in adipogenesis.
Scroyen
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I
Department of Molecular and Cellular Medicine, Center for Molecular and Vascular Biology, KU Leuven, Leuven, Belgium.
Christiaens
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V
Lijnen
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HR
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000637:transplantation; D050156:Adipogenesis / Q000187:drug effects; D000273:Adipose Tissue / Q000098:blood supply / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology; D004338:Drug Combinations; D005342:Fibrinolysis / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology; D007797:Laminin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008819:Mice, Nude; D018919:Neovascularization, Physiologic / Q000187:drug effects; D047495:PPAR gamma / Q000819:agonists; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011509:Proteoglycans / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection
D000911:Antibodies, Monoclonal; D004338:Drug Combinations; D007797:Laminin; D047495:PPAR gamma; D017395:Plasminogen Activator Inhibitor 1; D011509:Proteoglycans; D012333:RNA, Messenger; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D016222:Fibroblast Growth Factor 2; C059485:matrigel; D003094:Collagen