Factors regulating collagen synthesis and degradation during second-intention healing of wounds in the thoracic region and the distal aspect of the forelimb of horses.
OBJECTIVE
To determine significant molecular and cellular factors responsible for differences in second-intention healing in thoracic and metacarpal wounds of horses.


METHODS
6 adult mixed-breed horses.


METHODS
A full-thickness skin wound on the metacarpus and another such wound on the pectoral region were created, photographed, and measured, and tissue was harvested from these sites weekly for 4 weeks. Gene expression of type-I collagen, transforming growth factor (TGF)-beta1, matrix metalloproteinase (MMP)-1, and tissue inhibitor of metalloproteinase (TIMP)-1 were determined by quantitative in situ hybridization. Myofibroblasts were detected by immunohistochemical labeling with alpha-smooth muscle actin (alpha-SMA). Collagen accumulation was detected by use of picrosirius red staining. Tissue morphology was examined by use of H&E staining.


RESULTS
Unlike thoracic wounds, forelimb wounds enlarged during the first 2 weeks. Myofibroblasts, detected by week 1, remained abundant with superior organization in thoracic wounds. Type-I collagen mRNA accumulated progressively in both wounds. More type-I collagen and TGF-beta1 mRNA were seen in forelimb wounds. Volume of MMP-1 mRNA decreased from day 0 in both wounds. By week 3, TIMP-1 mRNA concentration was greater in thoracic wounds.


CONCLUSIONS
Greater collagen synthesis in metacarpal than thoracic wounds was documented by increased concentrations of myofibroblasts, type-I collagen mRNA,TGF-beta1 mRNA, and decreased collagen degradation (ie, MMP-1). Imbalanced collagen synthesis and degradation likely correlate with development of exuberant granulation tissue, delaying healing in wounds of the distal portions of the limbs. Factors that inhibit collagen synthesis or stimulate collagenase may provide treatment options for horses with exuberant granulation tissue.
Schwartz
Anne J
AJ
Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia 65221, USA.
Wilson
David A
DA
Keegan
Kevin G
KG
Ganjam
Venkataseshu K
VK
Sun
Yao
Y
Weber
Karl T
KT
Zhang
Jiakun
J
D000818:Animals; D001706:Biopsy / Q000662:veterinary; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D005552:Forelimb / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D006097:Granulation Tissue / Q000473:pathology; D006736:Horses / Q000378:metabolism / Q000502:physiology*; D007150:Immunohistochemistry / Q000662:veterinary; D017403:In Situ Hybridization / Q000662:veterinary; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D013898:Thoracic Injuries / Q000378:metabolism* / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
D024042:Collagen Type I; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; D020781:Matrix Metalloproteinase 1