The role of the tetraspanin CD151 in primary keratinocyte and fibroblast functions: implications for wound healing.
Previous studies showed that CD151-null mice have a skin wound healing deficit. To gain an understanding of the role of CD151 in re-epithelialisation and dermal contraction, keratinocyte and fibroblast functions were assayed. Primary CD151-null keratinocytes displayed defective migration on Matrigel (a basement membrane equivalent) and laminin-332, the primary adhesion component of basement membranes, but not on collagen-I. Adhesion, spreading and proliferation were also deficient on laminin-332, but not collagen-I. The data suggest that loss of CD151 impairs the function of its primary interaction partners, integrin alpha3beta1- and/or alpha6beta4 which bind to laminin-332. Skin fibroblasts also produce CD151 mRNA. CD151-null fibroblasts migrated significantly faster on collagen I than wild type fibroblasts, confirming that they possess functional collagen receptors. However, no significant decrease in the ability of CD151-null fibroblasts to cause contraction in floating collagen gel assays in response to transforming growth factor beta-1 (TGF-beta1) or platelet derived growth factor (PDGF-BB) was observed, nor was there an effect on fibroblast adhesion or proliferation on collagen-I. The data implicate CD151 as a facilitator of laminin-332-mediated keratinocyte functions that impact on the re-epithelialisation process intrinsic to wound healing and further suggest a potential novel role for CD151 in fibroblast migration.
School of Biomedical Sciences, University of Newcastle, New South Wales, Australia.
Sean M
SM
Geary
Allison J
AJ
Cowin
Ben
B
Copeland
Rosa M
RM
Baleato
Kaoru
K
Miyazaki
Leonie K
LK
Ashman
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D004338:Drug Combinations; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D006801:Humans; D039201:Integrin alpha3beta1 / Q000378:metabolism; D039161:Integrin alpha6beta4 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology*; D007797:Laminin / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011509:Proteoglycans / Q000378:metabolism; D060185:Tetraspanin 24; D014945:Wound Healing; D000097794:Kalinin
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D003094:Collagen; D024042:Collagen Type I; D004338:Drug Combinations; D039201:Integrin alpha3beta1; D039161:Integrin alpha6beta4; D007797:Laminin; D011509:Proteoglycans; D060185:Tetraspanin 24; D000097794:Kalinin; C554715:CD151 protein, human; C554716:Cd151 protein, mouse; C059485:matrigel