Integrin alpha2beta1 is required for regulation of murine wound angiogenesis but is dispensable for reepithelialization.
The alpha2beta1 integrin functions as the major receptor for collagen type I on a large number of different cell types, including keratinocytes, fibroblasts, endothelial cells, and a variety of inflammatory cells. Recently, we demonstrated that adhesion of keratinocytes to collagen critically depends on alpha2beta1, whereas fibroblasts can partly compensate for loss of alpha2beta1 in simple adhesion to collagen. However, in three-dimensional collagen matrices, alpha2beta1-null fibroblasts are hampered in generating mechanical forces. These data suggested a pivotal role for alpha2beta1 during wound healing in vivo. Unexpectedly, reepithelialization of excisional wounds of alpha2beta1-null mice was not impaired, indicating that keratinocytes do not require adhesion to or migration on collagen for wound closure. Whereas wound contraction and myofibroblast differentiation were similar, wound tensile strain was reduced in alpha2beta1-null mice, suggesting subtle changes in organization of the extracellular matrix. In addition, we observed reduced influx of mast cells into the granulation tissue, whereas infiltration of other inflammatory cells was not impaired. Interestingly, ablation of alpha2beta1 resulted in strong enhancement of neovascularization of granulation tissue and sponge implants. Both ultrastructurally and functionally, these new blood vessels appeared intact. In conclusion, our data show unique and overlapping functions of alpha2beta1 integrin during murine cutaneous wound healing.
Zweers
Manon C
MC
Department of Dermatology, University of Cologne, Cologne, Germany. manonzweers@gmail.com
Davidson
Jeffrey M
JM
Pozzi
Ambra
A
Hallinger
Ralf
R
Janz
Katharina
K
Quondamatteo
Fabio
F
Leutgeb
Barbara
B
Krieg
Thomas
T
Eckes
Beate
B
D000818:Animals; D002478:Cells, Cultured; D002921:Cicatrix / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D004848:Epithelium / Q000503:physiopathology; D005347:Fibroblasts; D038982:Integrin alpha2beta1 / Q000172:deficiency / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism; D008407:Mast Cells / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic; D012867:Skin / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology; D014945:Wound Healing; D014950:Wounds, Penetrating / Q000473:pathology / Q000503:physiopathology*
D038982:Integrin alpha2beta1; D016023:Integrins; D003094:Collagen