Down-regulating causes of fibrosis with tamoxifen: a possible cellular/molecular approach to treat rhinophyma.
Fibrosis and proliferative scarring are prominent features of the severe forms of rhinophyma. Up-regulation of growth and fibroblast kinetics are hallmarks of fibrosis. Persistent overexpression or dysregulated activation of the fibrogenic isoforms of transforming growth factor beta (TGF-beta) is associated with the increased fibroblast function leading to fibrotic conditions such as rhinophyma. Tamoxifen, a synthetic nonsteroidal antiestrogen, can neutralize or down-regulate TGF-beta. Fibroblast-populated collagen lattices (FPCLs) were constructed from fibroblasts cultured from rhinophyma or normal nasal skin. One-half of each set of FPCLs was treated with Tamoxifen. Lattice contraction was serially measured over 5 days, and the supernatants of the cultures were analyzed for TGF-beta-2 by immunoassay. Tamoxifen significantly decreased fibroblast activity by decreasing contraction of the treated lattices (P < 0.05) and significantly decreased the production/secretion of TGF-beta-2 by rhinophyma fibroblasts (P < 0.001). These results suggest a possible new cellular/molecular approach to the treatment of the fibrotic varieties of rhinophyma.
Payne
Wyatt G
WG
Institute for Tissue Regeneration, Repair, and Rehabilitation, Department of Veterans Administration Medical Center, Bay Pines, FL, USA.
Ko
Francis
F
Anspaugh
Stephanie
S
Wheeler
Chad K
CK
Wright
Terry E
TE
Robson
Martin C
MC
D016022:Case-Control Studies; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects; D015536:Down-Regulation; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects*; D005355:Fibrosis / Q000517:prevention & control; D006801:Humans; D008297:Male; D012224:Rhinophyma / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery; D012494:Sampling Studies; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D013629:Tamoxifen / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000187:drug effects / Q000378:metabolism*; D053781:Transforming Growth Factor beta2
D020845:Selective Estrogen Receptor Modulators; C509041:TGFB2 protein, human; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D013629:Tamoxifen