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Transforming growth factor- beta (TGF-beta) stimulates Type I collagen synthesis by fibroblasts and is implicated in tissue fibrosis. Here, we demonstrate that histone deacetylase inhibitor Trichostatin A (TSA) suppresses the TGF-beta-induced Type I collagen synthesis but not induced PAI-1 synthesis suggesting the influence of TSA is gene specific. Results further reveal that there is no significant alteration in Smad activation and function in presence of TSA suggesting suppression of TGF-beta-induced collagen synthesis is not due to impaired Smad signaling. TGF-beta induces the levels of Sp1, an essential transcription factor of Smad-dependent stimulation of collagen synthesis. However, in presence of TSA, TGF-beta fails to induce Sp1 levels, its interaction with Smad complex and Sp1 binding site in COL1A2 promoter. Furthermore, overexpressed Sp1 reverses the TSA-mediated inhibition of TGF-beta-induced collagen gene expression. Collectively, these results suggest that TSA-mediated suppression of Smad-dependent TGF-beta-induced collagen synthesis is due to suppression of Sp1 activity in skin fibroblasts.

Few data are available regarding endometrial histologic features in asymptomatic perimenopausal and postmenopausal women. This study encompasses endometrial biopsy specimens obtained from 801 such women before enrollment in a multicenter study of estrogen-progestin replacement. One endometrial cancer was found (0.13%); four additional biopsy specimens showed atypia (total 0.63%). The endometrium was atrophic in 373 (46.9%), proliferative in 133 (16.7%), secretory in 54 (6.8%), and hyperplastic in 41 (5.2%). Insufficient tissue for diagnosis was obtained in 195 (24.5%). We conclude that the yield for neoplasia is so low that screening endometrial biopsy is not justified in asymptomatic perimenopausal and postmenopausal women.