ABSTRACT
PURPOSE: To evaluate in vitro effects of tetrandrine on the TGF-ß-induced smad signal transduction pathway and cellular function altered by tetrandrine in human hypertrophic scar fibroblasts (HSFs). METHODS: HSFs were exposed to four different treatments (control, tetrandrine, TGF-ß(1) and mixture). After 48 h culture, expression of TGF-ß1, Smad2 and Smad7 were examined using reverse transcription PCR and Western blotting. To evaluate cellular function alteration, morphological changes of HSFs were observed under an inverted microscope, expression of type I and III collagen were tested by immunocytochemistry, and cell cycles were analyzed by flow cytometry. RESULTS: Expression of Smad7 increased while expression of Smad2 and TGF-ß1 mRNA decreased in HSFs with tetrandrine. In addition, type I and III collagen was suppressed and S phase of the cell cycle markedly shortened in HSFs by tetrandrine. CONCLUSIONS: These results suggest that tetrandrine inhibits HSFs at least partially through induction of Smad7 and decrement of Smad2 resulting in inhibition of TGF-ß1 transcription and its intracellular signaling, which led to reduction of type I and III collagen production and suppression of cell reproductive activity.
