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This Article Full Text Full Text (PDF) All Versions of this Article: 70/5/1246    most recent biolreprod.103.021956v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal My Folders Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lee, M.-J. Articles by Guller, S. Search for Related Content PubMed PubMed Citation Articles by Lee, M.-J. Articles by Guller, S. Agricola Articles by Lee, M.-J. Articles by Guller, S.

Glucocorticoid Enhances Transforming Growth Factor-ß Effects on Extracellular Matrix Protein Expression in Human Placental Mesenchymal Cells¹

Departments of Obstetrics and Gynecology³ Biochemistry,⁴ New York University School of Medicine, New York, New York 10016

Extracellular matrix (ECM) proteins synthesized by human placental mesenchymal cells (PMCs) provide structural support for the villus. Aberrant expression of ECM proteins by PMCs has been associated with intrauterine growth restriction (IUGR). To provide insight into the mechanisms of ECM protein regulation in the stroma of the placental villus, in the current study, we examined the interaction of glucocorticoid (GC) and transforming growth factor-ß (TGFß) in the modulation of ECM proteins in cultures of PMCs isolated from human term placentas. Initial results obtained by ELISA showed that combined treatment with dexamethasone (DEX) and TGFß enhanced oncofetal fibronectin (FFN) protein levels in serum-free culture medium severalfold in a dose-dependent manner. Northern blotting and real-time polymerase chain reaction (PCR) analyses revealed a similar enhancement in levels of FN mRNA in cells treated with TGFß and DEX. Real-time PCR results also revealed that DEX and TGFß enhanced collagen (Col) I and Col IV expression, but did not affect levels of Col III or laminin, indicative of selective stimulation of ECM proteins. Hypoxic treatment moderately enhanced FFN levels in control cells but not in those treated with DEX and TGFß. In contrast with the results obtained with PMCs, we noted that DEX treatment suppressed FFN levels in untreated and TGFß-treated cytotrophoblasts, suggesting that GC and TGFß modulate FFN expression in placenta in a cell-type-specific manner. We conclude that GC and TGFß are key regulators of ECM protein synthesis in PMCs, suggesting a role in modulating placental architecture in uncomplicated pregnancies and those associated with aberrant ECM protein expression.

¹ These studies were supported in part through NIH grant HD 33909 (S.G.). M.J.L. is the recipient of a NICHD Reproductive Scientist Development Program (K12-HD 00849)/Wyeth Scholarship.

² Correspondence and current address: Seth Guller, Yale University School of Medicine, Department of OB/GYN, 333 Cedar Street - 339 FMB, P.O. Box 208063, New Haven, CT 06520-8063. FAX: 203 785 4713; seth.guller{at}yale.edu

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