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.
Department of Pathology, University of Michigan Medical School, 1301 Catherine Street, SPC 5602, Ann Arbor, MI 48109, USA. varani@umich.edu
James
J
Varani
Patricia
P
Perone
Monica O'Brien
MO
Deming
Roscoe L
RL
Warner
Muhammad N
MN
Aslam
Narasimharao
N
Bhagavathula
Michael K
MK
Dame
John J
JJ
Voorhees
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