In wound healing
transforming growth factor β1 (TGFβ1), utilizing the Smad signaling pathway, advances connective tissue deposition, the transformation of fibroblasts into myofibroblasts and
wound contraction. The compound
SB-505124 disrupts the Smad signaling pathway by blocking
activin receptor-like kinase phosphorylation of select Smad signaling
proteins. Four full thickness excisional square 2×2 cm
wounds were made on the rat dorsum. On day 2, the pair of
wounds on the left received 1 μM
SB-505124 in gel, and the pair on the right, controls, received gel alone.
Wounds were covered with nonocclusive dressings and treated redressed daily for 4 days. No differences in day 14
wound sizes between treatment groups were found. H&E stained sections revealed increased cell density in
SB-505124 treated
wounds. Polarized light microscopy showed
collagen fiber bundles birefringence intensity and organization were equivalent between treatment groups. Myofibroblast populations, identified by α-smooth muscle actin staining, were the norm in controls but absent in
SB-505124 treated
wounds, which was confirmed by Western blot analysis. Blocking the Smad signaling pathway diminished connective tissue deposition and generated a deficiency in myofibroblast numbers, but
wound contraction was unimpaired. The absence of myofibroblasts may be related to the blocking of the Smad signaling pathway or it may be related to the generation of less tension in treated
wounds, related to reduce deposited connective tissue. These findings support the notion that
wound contraction does not require the generation of myofibroblast contractile forces, but rather the organization of newly deposited
collagen fiber bundles by forces related to fibroblast locomotion.