Impaired wound contraction and delayed myofibroblast differentiation in restraint-stressed mice

Previous research has shown that psychological stress delays wound closure by >25%. Gene expression of pro-inflammatory cytokines and the maturation of the epithelium were also impaired by stress (Mercado et al.). Wound contraction contributes to the speed of wound closure (Hunt and Hopf). In the current study, wound contraction was decreased by >45% (p<.01) in restraint stressed mice. Fibroblast migration and differentiation into smooth muscle alpha-actin (Sm alpha A) -expressing myofibroblasts were delayed in RST mice through day 7 post-wounding. In addition, there was a 25 (p <.01), 48 (p <.01), and 38% (P <.05) decrease in SmotA mRNA levels at days 1, 3, and 5 post-wounding in RST mice, respectively. Cytokines that regulate fibroblast migration and differentiation include transforming growth factors-beta 1, -beta 2, and -beta 3 ((TGF-beta s). Although expression of TGF-beta 1 mRNA was downregulated by >25% (p <.01) in RST mice on day 3 post-wounding, no significant differences were detected in active or total TGF-beta 1 protein levels. Stress did not alter the expression of TGF-beta 2 or -beta 3 through day 5 post-wounding. Thus, these data indicate that stress delays wound contraction and myofibroblast differentiation, which are likely independent of expression of TGF-beta 1, -beta 2, and -beta 3. (C) 2004 Elsevier Inc. All rights reserved.