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Ectopic localization of matrix metalloproteinase-9 in chronic cutaneous wounds.

Mirastschijski, Ursula LU ; Impola, Ulla; Jahkola, Tiina; Karlsmark, Tonny; AGren, Magnus S and Saarialho-Kere, Ulpu (2002) In Human Pathology 33(3). p.355-364
Abstract
It has been hypothesized that excessive activity of matrix metalloproteinases (MMPs), in particular the gelatinases MMP-9 and MMP-2, contributes to poor healing of chronic skin ulcers. We compared MMP-9 and MMP-2 in wound margin biopsies of standardized acute partial-thickness wounds in healthy volunteers (n = 6) and in venous leg ulcer patients (n = 12) with those of chronic wounds of different etiologies (n = 34) by a combination of specific analyses of activity and protein localization. We also studied MMP-14 by immunohistochemistry and in situ hybridization in parallel. Neither MMP-9 (P =.814) nor MMP-2 (P =.742) endogenous activities differed significantly between acute and chronic wound tissues. Acute wound healing was characterized... (More)
It has been hypothesized that excessive activity of matrix metalloproteinases (MMPs), in particular the gelatinases MMP-9 and MMP-2, contributes to poor healing of chronic skin ulcers. We compared MMP-9 and MMP-2 in wound margin biopsies of standardized acute partial-thickness wounds in healthy volunteers (n = 6) and in venous leg ulcer patients (n = 12) with those of chronic wounds of different etiologies (n = 34) by a combination of specific analyses of activity and protein localization. We also studied MMP-14 by immunohistochemistry and in situ hybridization in parallel. Neither MMP-9 (P =.814) nor MMP-2 (P =.742) endogenous activities differed significantly between acute and chronic wound tissues. Acute wound healing was characterized by induction of MMP-9 in the advancing epithelium. In chronic wounds, prominent MMP-9 immunostaining was seen in neutrophils and macrophages in the ulcer bed, but virtually no MMP-9 was detected in wound edge keratinocytes. MMP-2 was increased and activated with acute wound age. MMP-2 was found abundantly in dermal fibroblasts and endothelial cells beneath, but not in new epithelium of acute and chronic wounds. MMP-14 mRNA or protein was detected solely in the stroma of both acute and chronic wounds. In conclusion, the overall activity of gelatinases MMP-9 and MMP-2 was not increased in chronic wounds compared to normally healing wound tissues. Chronic nonhealing wounds may not be caused by excessive gelatinase activity, but are distinguished from healing wounds by an unfavorable distribution and persistance of MMP-9. (Less)
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keywords
Gelatinase A : genetics, Female, Chronic Disease, Cultured, Cells, 80 and over, Aged, Adult, Acute Disease, Leg Ulcer : pathology, Male, Metalloendopeptidases : genetics, Metalloendopeptidases : metabolism, Middle Age, Messenger : metabolism, RNA, Skin : enzymology, Skin : injuries, Skin : pathology, Support, Non-U.S. Gov't, Wounds and Injuries : pathology, Wound Healing : physiology, Wounds and Injuries : enzymology, Gelatinase A : metabolism, Gelatinase B : genetics, Gelatinase B : metabolism, Human, Immunohistochemistry, In Situ Hybridization, Leg Ulcer : enzymology
in
Human Pathology
volume
33
issue
3
pages
355 - 364
publisher
Elsevier
external identifiers
  • wos:000175340300014
  • pmid:11979378
  • scopus:0036239786
ISSN
1532-8392
DOI
10.1053/hupa.2002.32221
language
English
LU publication?
yes
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f08c4f3e-69df-49f5-a131-646b02aff3d2 (old id 107853)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11979378&dopt=Abstract
date added to LUP
2007-07-26 13:56:45
date last changed
2017-10-22 03:46:59
@article{f08c4f3e-69df-49f5-a131-646b02aff3d2,
  abstract     = {It has been hypothesized that excessive activity of matrix metalloproteinases (MMPs), in particular the gelatinases MMP-9 and MMP-2, contributes to poor healing of chronic skin ulcers. We compared MMP-9 and MMP-2 in wound margin biopsies of standardized acute partial-thickness wounds in healthy volunteers (n = 6) and in venous leg ulcer patients (n = 12) with those of chronic wounds of different etiologies (n = 34) by a combination of specific analyses of activity and protein localization. We also studied MMP-14 by immunohistochemistry and in situ hybridization in parallel. Neither MMP-9 (P =.814) nor MMP-2 (P =.742) endogenous activities differed significantly between acute and chronic wound tissues. Acute wound healing was characterized by induction of MMP-9 in the advancing epithelium. In chronic wounds, prominent MMP-9 immunostaining was seen in neutrophils and macrophages in the ulcer bed, but virtually no MMP-9 was detected in wound edge keratinocytes. MMP-2 was increased and activated with acute wound age. MMP-2 was found abundantly in dermal fibroblasts and endothelial cells beneath, but not in new epithelium of acute and chronic wounds. MMP-14 mRNA or protein was detected solely in the stroma of both acute and chronic wounds. In conclusion, the overall activity of gelatinases MMP-9 and MMP-2 was not increased in chronic wounds compared to normally healing wound tissues. Chronic nonhealing wounds may not be caused by excessive gelatinase activity, but are distinguished from healing wounds by an unfavorable distribution and persistance of MMP-9.},
  author       = {Mirastschijski, Ursula and Impola, Ulla and Jahkola, Tiina and Karlsmark, Tonny and AGren, Magnus S and Saarialho-Kere, Ulpu},
  issn         = {1532-8392},
  keyword      = {Gelatinase A : genetics,Female,Chronic Disease,Cultured,Cells,80 and over,Aged,Adult,Acute Disease,Leg Ulcer : pathology,Male,Metalloendopeptidases : genetics,Metalloendopeptidases : metabolism,Middle Age,Messenger : metabolism,RNA,Skin : enzymology,Skin : injuries,Skin : pathology,Support,Non-U.S. Gov't,Wounds and Injuries : pathology,Wound Healing : physiology,Wounds and Injuries : enzymology,Gelatinase A : metabolism,Gelatinase B : genetics,Gelatinase B : metabolism,Human,Immunohistochemistry,In Situ Hybridization,Leg Ulcer : enzymology},
  language     = {eng},
  number       = {3},
  pages        = {355--364},
  publisher    = {Elsevier},
  series       = {Human Pathology},
  title        = {Ectopic localization of matrix metalloproteinase-9 in chronic cutaneous wounds.},
  url          = {http://dx.doi.org/10.1053/hupa.2002.32221},
  volume       = {33},
  year         = {2002},
}