Loss of epidermal MMP-14 expression interferes with angiogenesis but not with re-epithelialization.
Synthesis and activation of matrix metalloproteinases during wound healing are important for remodeling the extracellular matrix and modulating various cellular functions. The membrane-type 1 matrix metalloproteinase (MMP-14) has been shown to play a key role during these processes. To analyze the function of epidermal-derived MMP-14 during skin repair we generated mice lacking MMP-14 expression in the epidermis (MMP-14(ep-/-)). These mice displayed overall normal skin morphology and epidermal differentiation patterns. Wound repair in MMP-14(ep-/-) followed the same kinetics as in wild type mice (MMP-14(ep+/+)), and infiltration of neutrophils, leukocytes, and macrophages into the wound site was comparable. Microscopic analysis showed no altered re-epithelialization in the absence of epidermal MMP-14. Furthermore, epidermal differentiation at the end of the repair process and scar formation was normal. However, at day 14 post wounding, sustained angiogenesis was observed in MMP-14(ep-/-) mice in contrast to control mice. Interestingly, decreased levels of endostatin were detected in wound lysates of MMP-14(ep-/-) mice as well as in cultured keratinocytes. Taken together, these data indicate that MMP-14 expression in keratinocytes is dispensable for skin homeostasis and repair, but plays a crucial role in the epidermal-dermal crosstalk leading to modulation of vessel density.
Department of Dermatology and Venerology, University of Cologne, Germany. Paola.Zigrino@uni-koeln.de
Paola
P
Zigrino
Ouissam
O
Ayachi
Alexander
A
Schild
Jennifer
J
Kaltenberg
Jan
J
Zamek
Roswitha
R
Nischt
Manuel
M
Koch
Cornelia
C
Mauch
D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D003094:Collagen / Q000378:metabolism; D043169:Endostatins / Q000235:genetics / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000201:enzymology / Q000293:injuries / Q000502:physiology*; D015870:Gene Expression; D015603:Keratinocytes / Q000166:cytology / Q000201:enzymology / Q000502:physiology; D007962:Leukocytes / Q000502:physiology; D008264:Macrophages / Q000502:physiology; D053511:Matrix Metalloproteinase 14 / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic; D009504:Neutrophils / Q000502:physiology; D062326:Re-Epithelialization
D043169:Endostatins; C507096:Mmp14 protein, mouse; D003094:Collagen; D053511:Matrix Metalloproteinase 14