Impaired keratinocyte function on matrix metalloproteinase-1 (MMP-1) damaged collagen.
Healing of superficial skin wounds depends on the proliferation and migration of keratinocytes at the wound margin. When human epidermal keratinocytes were incubated on polymerized type I collagen, they rapidly attached and spread. The cells underwent a proliferative response and, over the subsequent 6-day period, covered the collagen surface with a monolayer of cells. When keratinocytes were plated on collagen that had been fragmented by exposure to matrix metalloproteinase-1 (MMP-1, collagenase-1), the cells attached as readily as to intact collagen but spread more slowly and less completely. Growth was reduced by approximately 50%. Instead of covering the collagen surface, the keratinocytes remained localized to the site of attachment. Keratinocytes on fragmented collagen expressed a more differentiated phenotype as indicated by a higher level of surface E-cadherin. Based on these findings, we suggest that damage to the underlying collagenous matrix may impede efficient keratinocyte function and retard wound closure.
Varani
James
J
Department of Pathology, University of Michigan Medical School, 1301 Catherine Street, SPC 5602, Ann Arbor, MI 48109, USA. varani@umich.edu
Perone
Patricia
P
Deming
Monica O'Brien
MO
Warner
Roscoe L
RL
Aslam
Muhammad N
MN
Bhagavathula
Narasimharao
N
Dame
Michael K
MK
Voorhees
John J
JJ
D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation; D048708:Cell Growth Processes / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism*; D017364:Collagenases / Q000378:metabolism / Q000494:pharmacology; D003599:Cytoskeleton; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism* / Q000494:pharmacology; D011108:Polymers / Q000378:metabolism*; D014945:Wound Healing / Q000187:drug effects
D015820:Cadherins; D024042:Collagen Type I; D011108:Polymers; D017364:Collagenases; C417249:collagenase 1; D020781:Matrix Metalloproteinase 1