Wound-healing defects in mice lacking fibrinogen.
In addition to its key role in the control of blood loss following injury, fibrin(ogen) has been proposed to play an important role in tissue repair by providing an initial matrix that can stabilize wound fields and support local cell proliferation and migration. To test directly these concepts, the effect of fibrinogen deficiency on cutaneous tissue repair in mice was investigated using incisional and excisional wounds. The time required to overtly heal wounds was similar in fibrinogen-deficient and control mice, but histologic evaluation revealed distinct differences in the repair process, including an altered pattern of epithelial cell migration and increased epithelial hyperplasia. Furthermore, granulation tissue in fibrinogen-deficient mice failed to adequately close the wound gap, resulting in persistent open wounds or partially covered sinus tracts. The tensile strength of these wounds was also reduced compared with control mice. The most profound defect in wound tissue organization was observed in fibrinogen-deficient mice following the subcutaneous implantation of a porous tubing chamber. Cells migrated into the wall of the implants at a similar rate as control mice, but cells from fibrinogen-deficient animals were unable to efficiently organize and migrate into wound fluid-filled dead space within the center of the implants. These studies show that re-epithelialization, granulation tissue formation, including the establishment of neovasculature, and the formation of fibrotic scar tissue can proceed in the absence of fibrin(ogen) and all of its proteolytic derivatives. However, fibrin (ogen) is important for appropriate cellular migration and organization within wound fields and in initially establishing wound strength and stability. (Blood. 2001;97:3691-3698)
Drew
A F
AF
Division of Developmental Biology, Children's Hospital Research Foundation, 3333 Burnet Ave., Cincinnati, PH 45229-3039, USA.
Liu
H
H
Davidson
J M
JM
Daugherty
C C
CC
Degen
J L
JL
D000818:Animals; D002465:Cell Movement; D004847:Epithelial Cells / Q000166:cytology; D004848:Epithelium / Q000473:pathology; D005340:Fibrinogen / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D006909:Hydroxyproline / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D013718:Tensile Strength / Q000187:drug effects; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
D005340:Fibrinogen; D006909:Hydroxyproline