When the Smad signaling pathway is impaired, fibroblasts advance open wound contraction.
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.
Au
Katherine
K
Division of Plastic Surgery, Penn State University College of Medicine, MS Hershey Medical Center, Hershey, PA 17033, USA.
Ehrlich
H Paul
HP
D000818:Animals; D015153:Blotting, Western; D005347:Fibroblasts / Q000378:metabolism*; D006097:Granulation Tissue / Q000378:metabolism; D008297:Male; D058628:Myofibroblasts / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D051785:Smad Proteins / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology*
D051785:Smad Proteins