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Autocrine regulation of human preadipocyte migration by plasminogen activator inhibitor-1.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Crandall, David L. Busler, Dennis E. Mchendry-Rinde, Barbara Groeling, Thomas M. Kral, John G. |
| Copyright Year | 2000 |
| Abstract | One of the initial stages of adipogenesis is migration of preadipocytes of mesenchymal origin into cell clusters to form primitive fat organs. The serine protease inhibitor plasminogen activator inhibitor-1 (PAI-1) is synthesized and released from human adipose tissue ex vivo and regulates smooth muscle and endothelial cell migration in vitro, but its role in adipose tissue is not known. We investigated the role of PAI-1 in cultures of human preadipocytes from men and women of various ages and body mass indexes. Human preadipocytes expressed the messenger ribonucleic acid for PAI-1 and released significant quantities of PAI-1 protein into the medium. As PAI-1 regulates motility through the interaction of vitronectin with its receptor, the integrin alphaVbeta3, we identified this receptor in human preadipocytes. Flow cytometric analysis indicated that human preadipocytes express the vitronectin receptor alphaVbeta3 in a similar pattern as human umbilical vein endothelial cells. Functional studies indicated that active, but not latent, PAI-1 inhibited preadipocyte attachment to vitronectin with an IC(50) of 13.3 nmol/L, and preincubation of vitronectin-coated Transwells with active PAI-1 prevented preadipocyte migration. Vitronectin was identified in homogenates of the stromal-vascular fraction of human adipose tissue, but was absent from human adipocytes and cultured preadipocytes. These data indicate that human preadipocyte migration is regulated through the endogenous expression of PAI-1 and alphaVbeta3 integrin, a novel autocrine mechanism for potentially regulating cell cluster formation in adipogenesis. |
| Starting Page | 350 |
| Ending Page | 355 |
| Page Count | 6 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://jcem.endojournals.org/content/85/7/2609.full.pdf |
| PubMed reference number | 10902815v1 |
| Volume Number | 85 |
| Issue Number | 7 |
| Journal | The Journal of clinical endocrinology and metabolism |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Adipocytes Adipogenesis Adipose tissue Cell cluster Endopeptidases Endothelial Cells Integrin alphaVbeta3 Organ Plasminogen Activator Platelet Glycoprotein 4, human Protease Inhibitors Quantity RNA RNA, Messenger SERPINE1 protein, human Serine Proteases Serine Proteinase Inhibitors Smooth muscle (tissue) Umbilical vein Umbilicus (Anatomy) VTN gene alteplase autocrine |
| Content Type | Text |
| Resource Type | Article |