Basic fibroblast growth factor induces down‐regulation of α‐smooth muscle actin and reduction of myofibroblast areas in open skin wounds

Abstract

To examine the effects of basic fibroblast growth factor (bFGF) on the inhibition of alpha-smooth muscle actin (alpha-SMA) expression in dermal fibroblasts, we have established two dermal myofibroblastic cell lines positive for alpha-SMA (rat myofibroblasts [RMF] and rat myofibroblast-like [RMFL] cells) and one fibroblastic cell line negative for alpha-SMA (rat fibroblasts cells) as a model of fibroblast differentiation. In contrast to the increased expression of alpha-SMA in RMF and RMFL cells, irrespective of transforming growth factor-beta1 treatment, bFGF induced a decrease in alpha-SMA expression in the myofibroblastic cells and the reduced expression patterns of alpha-SMA differed between cells, as demonstrated by Western blot and reverse transcription polymerase chain reaction analyses. Along with the inhibition of alpha-SMA expression by bFGF, the RMF and RMFL cells also showed different activated expression of extracellular signal-regulated kinase 1/2, suggesting the involvement of extracellular signal-regulated kinase 1/2 activation in the down-regulation of alpha-SMA expression in myofibroblasts. Furthermore, an in vivo study demonstrated that bFGF administration markedly decreases the area that is positive for alpha-SMA expression in the treated wounds after day 18. In contrast, bFGF administration significantly increased the number of terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) staining and alpha-SMA-positive cells at days 10 and 14, and reduced the double-positive cells rapidly after day 18. Collectively, the current investigation identified bFGF as a potent stimulator for the reduction of the myofibroblastic area in vivo, presumably because of its effects on the down-regulation of alpha-SMA expression as well as rapid induction of apoptosis in myofibroblasts.