Effect of tetrandrine on the TGF-β-induced smad signal transduction pathway in human hypertrophic scar fibroblasts in vitro.

PURPOSE: To evaluate in vitro effects of tetrandrine on the TGF-β-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-β(1) and mixture). After 48 h culture, expression of TGF-β1, 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-β1 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-β1 transcription and its intracellular signaling, which led to reduction of type I and III collagen production and suppression of cell reproductive activity.