Accelerated wound repair in ADAM-9 knockout animals.
ADAM-9 belongs to a family of transmembrane, disintegrin-containing metalloproteinases (ADAMs) involved in protein ectodomain shedding and cell-cell and cell-matrix interactions. Although the functions of many ADAM family members are known, the specific biological function of ADAM-9 is still unclear. In this study, we have analyzed ADAM-9 temporal and spatial distribution during wound healing. We showed increased ADAM-9 transcript expression during the first 7 days post-wounding and, by immunolocalization, detected ADAM-9 in all migrating and proliferating keratinocytes from days 3 to 7. In older 14-day-old wounds, ADAM-9 expression was restored. We have investigated the role of this protein in the healing process following excisional wounding. Animals deficient in ADAM-9 showed accelerated wound repair compared with control littermates. No alterations in neutrophil, leukocyte, and macrophage infiltration were observed. However, re-epithelialization was significantly faster in Adam-9 -/- than control wounds. Although no differences in proliferation were observed in vivo and in vitro, increased migration of keratinocytes was responsible for this effect. These results show the previously unreported role of ADAM-9 in wound repair by regulating keratinocyte migration through modulation of collagen XVII shedding.
Mauch
Cornelia
C
Department of Dermatology and Center for Molecular Medicine (CMMC), University of Cologne, Cologne, Germany.
Zamek
Jan
J
Abety
Anna N
AN
Grimberg
Gundula
G
Fox
Jay W
JW
Zigrino
Paola
P
D051722:ADAM Proteins / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001324:Autoantigens / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D002908:Chronic Disease; D000078404:Epidermal Cells; D015870:Gene Expression / Q000502:physiology; D006097:Granulation Tissue / Q000502:physiology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024041:Non-Fibrillar Collagens / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000293:injuries*; D012883:Skin Ulcer / Q000473:pathology / Q000503:physiopathology; D014945:Wound Healing / Q000502:physiology*; D000097805:Collagen Type XVII
D051722:ADAM Proteins; D001324:Autoantigens; D008565:Membrane Proteins; D024041:Non-Fibrillar Collagens; D012333:RNA, Messenger; D000097805:Collagen Type XVII; C498316:Adam9 protein, mouse