TRANSFORMING GROWTH-FACTOR-BETA-1 MODULATES MYOFIBROBLASTIC PHENOTYPEOF RAT PALATAL FIBROBLASTS IN-VITRO

The effects of transforming growth factor-beta 1 (TGF-beta 1) on norma l rat palatal fibroblasts in vitro were investigated in the present st udy in order to unravel the precise mechanisms by which the phenotypic modulation of fibroblasts occurs during the scar formation process, T GF-beta 1 dramatically changed the morphology of normal palatal fibrob lasts from polygonal into an elongated shape, which was very similar t o that of fibroblasts derived from experimental immature scar tissue i n rat palatal mucosa. This morphological transition was concomitant wi th an increase in the expression of alpha-smooth muscle (alpha-SM) act in protein, a marker for myofibroblasts, when determined by immunocyto chemistry. An immunoblot study also revealed that alpha-SM actin expre ssion in palatal fibroblasts became evident after 24 h of TGF-beta 1 t reatment and increased time-dependently up to 72 h. Northern blot anal ysis showed that TGF-beta 1 stimulated endogenous TGF-beta 1 mRNA expr ession in palatal fibroblasts within 24 h. Neither epidermal growth fa ctor nor basic fibroblast growth factor had any effect on either alpha -SM actin expression or TGF-beta 1 mRNA expression. Pretreatment of pa latal fibroblasts with TGF-beta 1 significantly increased the contract ile capacity in a three-dimensional collagen gel culture, even when th e culture medium was deprived of TGF-beta 1 for 72 h of the experiment al period, Moreover, the contractility of scar fibroblasts, which high ly expressed alpha-SM actin protein and TGF-beta 1 mRNA, was significa ntly lowered by a neutralizing antibody to TGF-beta 1. These data stro ngly suggest that TGF-beta 1 is a potential inducer of phenotypic expr ession of myofibroblasts in palatal fibroblasts and that autoinduction of TGF-beta 1 mRNA expression may play an important role in the scar formation process in palatal mucosa. (C) 1997 Academic Press.