Basic fibroblast growth factor induces down-regulation of alpha-smooth muscle actin and reduction of myofibroblast areas in open skin wounds.
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.
Ishiguro
Shigeki
S
Department of Pathology, School of Medicine, Toho University, Ohta-City, Tokyo 143-8540, Japan.
Akasaka
Yoshikiyo
Y
Kiguchi
Hideko
H
Suzuki
Takeya
T
Imaizumi
Risa
R
Ishikawa
Yukio
Y
Ito
Kinji
K
Ishii
Toshiharu
T
D000199:Actins / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D015536:Down-Regulation; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D005347:Fibroblasts / Q000502:physiology*; D051381:Rats; D012867:Skin / Q000293:injuries*; D014945:Wound Healing / Q000502:physiology*
D000199:Actins; D016222:Fibroblast Growth Factor 2; C498862:Acta2 protein, rat