Collagenase‐2 (MMP‐8) and matrilysin‐2 (MMP‐26) expression in human wounds of different etiologies
Abstract
Wound healing involves highly controlled events including reepithelialization, neoangiogenesis, and reformation of the stromal compartment. Matrix metalloproteinases (MMPs) are a family of neutral zinc‐dependent endopeptidases known to be essential for the wound‐healing process. MMP‐8 (collagenase‐2) is a neutrophil‐derived highly effective type I collagenase, recently indicated to be important for acute wound healing. MMP‐26 is a more recent and less well‐studied member of the MMP family. Our aim was to study the expression of MMP‐8 and MMP‐26 in human cutaneous wound repair and chronic wounds using histological methods and cell culture. MMP‐8 expression was associated with epithelial cells, neutrophils, and other inflammatory cells in chronic human wounds. MMP‐26 was prominently expressed in the extracellular compartment of most chronic wounds in close vicinity to the basement membrane area. MMP‐26 was also expressed in acute day 1 wounds with declining expression thereafter. In vitro wound experiments showed that both MMP‐8 and MMP‐26 were expressed by migrating human mucosal keratinocytes. Inhibiting MMP‐26 resulted in aberrant keratinocyte migration and proliferation. We conclude that MMP‐8 and MMP‐26 are differentially expressed in acute and chronic wounds.
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Neutrophil-derived proteases such as elastase and matrix metalloproteinases can degrade healthy extracellular matrix, and increased levels of these proteases have been repeatedly detected in chronic wounds.
“neutrophil-derived proteases, such as elastase and matrix metalloproteinases (MMPs), can degrade healthy extracellular matrix (ECM), and increased levels of these proteases have been repeatedly detected in chronic wounds [52–56].”
From Immunology of Wound Healing (2018) · cites this paper as [56]
Cites
Wound Healing--Aiming for Perfect Skin Regeneration
Martin, P. B. (1997) · Science · doi:10.1126/science.276.5309.75 · Cited by 4,814 · see citing works
Human and mouse proteases: a comparative genomic approach
Puente, X. S., Sánchez, L. M., Overall, C. M., & López-Otı́n, C. (2003) · Nature Reviews Genetics · doi:10.1038/nrg1111 · Cited by 940 · see citing works
Protease degradomics: A new challenge for proteomics
López-Otı́n, C., & Overall, C. M. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm858 · Cited by 748 · see citing works
Lobmann, R., Ambrosch, A., Schultz, G. S., Waldmann, K., Schiweck, S., & Lehnert, H. (2002) · Diabetologia · doi:10.1007/s00125-002-0868-8 · Cited by 616 · see citing works
The Activity of Collagenase-1 Is Required for Keratinocyte Migration on a Type I Collagen Matrix
Pilcher, B. K., Dumin, J. A., Sudbeck, B. D., Krane, S. M., Welgus, H. G., & Parks, W. C. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.137.6.1445 · Cited by 613 · see citing works
Tumor targeting with a selective gelatinase inhibitor
Koivunen, E., Arap, W., Valtanen, H., Rainisalo, A., Medina, O. P., Heikkilä, P., Kantor, C., Gahmberg, C. G., Salo, T. A., Konttinen, Y. T., et al. (1999) · Nature Biotechnology · doi:10.1038/11703 · Cited by 567 · see citing works
Self-citationLoss of collagenase-2 confers increased skin tumor susceptibility to male mice
Balbı́n, M., Fueyo, A., Tester, A. M., Pendás, A. M., Pitiot, A. S., Astudillo, A., Overall, C. M., Shapiro, S. D., & López-Otı́n, C. (2003) · Nature Genetics · doi:10.1038/ng1249 · Cited by 536 · see citing works
Matrix Metalloproteinase-8 Is Expressed in Rheumatoid Synovial Fibroblasts and Endothelial Cells
Hanemaaijer, R., Sorsa, T. A., Konttinen, Y. T., Ding, Y., Sutinen, M. M., Visser, H., van Hinsbergh, V. W. M., Helaakoski, T., Kainulainen, T., Rönkä, H., et al. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.50.31504 · Cited by 489 · see citing works
Self-citationExpression of matrix metalloproteinase-2 and -9 during early human wound healing.
Salo, T. A., Mäkelä, M., Kylmäniemi, M., Autio‐Harmainen, H., & Larjava, H. (1994) · PubMed · Cited by 406 · see citing works
Self-citationHasty, K. A., Pourmotabbed, T., Goldberg, G. I., Thompson, J. P., Spinella, D. G., Stevens, R., & Mainardi, C. L. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)38413-3 · Cited by 401 · see citing works
MMP-8 Is the Predominant Collagenase in Healing Wounds and Nonhealing Ulcers
Nwomeh, B. C., Liang, H.-X., Cohen, I. K., & Yager, D. R. (1999) · Journal of Surgical Research · doi:10.1006/jsre.1998.5495 · Cited by 357 · cited 1× · see citing works
“In humans, MMP-8 is 100-fold increased in chronic wound fluids compared with acute wounds, although the implication of this is still unknown.(11) MMP-26 (matrilysin-2) is abundantly expressed in the human placenta, uterus,(12,13) endometrial glandular cells,(14) kidney,(15) the gastrointestinal tract,(16) and epitheli…”
BackgroundVaalamo, M., Mattila, L., Johansson, N., Kariniemi, A., Karjalainen‐Lindsberg, M., Kähäri, V., & Saarialho‐Kere, U. (1997) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12276722 · Cited by 287 · see citing works
Self-citationFunctional overlap between two classes of matrix‐degrading proteases in wound healing
Lund, L. R., Rømer, J., Bugge, T. H., Nielsen, B. S., Frandsen, T. L., Degen, J. L., Stephens, R. W., & Danø, K. (1999) · The EMBO Journal · doi:10.1093/emboj/18.17.4645 · Cited by 270 · see citing works
Matrilysin expression and function in airway epithelium.
Dunsmore, S. E., Saarialho‐Kere, U., Roby, J. D., Wilson, C. L., Matrisian, L. M., Welgus, H. G., & Parks, W. C. (1998) · Journal of Clinical Investigation · doi:10.1172/jci1516 · Cited by 270 · see citing works
Self-citationOwen, C. A., Hu, Z., López-Otı́n, C., & Shapiro, S. D. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.12.7791 · Cited by 257 · see citing works
Tervahartiala, T. I., Pirilä, E., Čeponis, A., Maisi, P., Salo, T. A., Tüter, G., Kallio, P., Törnwall, J., Srinivas, R., Konttinen, Y. T., et al. (2000) · Journal of Dental Research · doi:10.1177/00220345000790120801 · Cited by 226 · see citing works
Self-citationUrı́a, J. A., & López-Otı́n, C. (2000) · PubMed · Cited by 208 · see citing works
Pathophysiology of Chronic Nonhealing Wounds
Medina, A., Scott, P. G., Ghahary, A., & Tredget, E. E. (2005) · Journal of Burn Care & Rehabilitation · doi:10.1097/01.bcr.0000169887.04973.3a · Cited by 204 · see citing works
Vaalamo, M., Weckroth, M., Puolakkainen, P. A., Kere, J., Saarinen, P., Lauharanta, J., & Saarialho‐Kere, U. (1996) · PubMed · Cited by 199 · see citing works
Self-citationPark, H. I., Ni, J., Gerkema, F. E., Liu, D., Belozerov, V. E., & Sang, Q. A. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m002349200 · Cited by 195 · see citing works
A Genomic Analysis of Rat Proteases and Protease InhibitorsPreprint
Puente, X. S., & López-Otı́n, C. (2004) · Genome Research · doi:10.1101/gr.1946304 · Cited by 192 · see citing works
Treatment with human metalloproteinase-8 gene delivery ameliorates experimental rat liver cirrhosis
Siller-López, F., Sandoval-Rodriguez, A. S., Salgado, S., Salazar, A., Bueno‐Topete, M. R., Garcı́a, J., Vera-Cruz, J. M., Gálvez, J., Hernández‐Cañaveral, I., & Ramos, M. H. (2004) · Gastroenterology · doi:10.1053/j.gastro.2003.12.045 · Cited by 173 · see citing works
Montel, V., Kleeman, J. E., Agarwal, D., Spinella, D. G., Kawai, K., & Tarin, D. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-2047 · Cited by 169 · see citing works
MARCHENKO, G. N., Ratnikov, B. I., Rozanov, D. V., Godzik, A., Deryugina, E. I., & Strongin, A. Y. (2001) · Biochemical Journal · doi:10.1042/0264-6021:3560705 · Cited by 147 · see citing works
Krampert, M., Bloch, W., Sasaki, T., Bugnon, P., Rülicke, T., Wolf, E., Aumailley, M., Parks, W. C., & Werner, S. (2004) · Molecular Biology of the Cell · doi:10.1091/mbc.e04-02-0109 · Cited by 145 · see citing works
[26] Human neutrophil collagenase
Tschesche, H. (1995) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(95)48028-5 · Cited by 131 · see citing works
Zhao, Y.-G., Xiao, A.-Z., Newcomer, R. G., Park, H. I., Kang, T., Chung, L. W. K., Swanson, M. G., Zhau, H. E., Kurhanewicz, J. V., & Sang, Q. A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210975200 · Cited by 129 · see citing works
Overview: Acute and Chronic Wounds
Whitney, J. D. (2005) · Nursing Clinics of North America · doi:10.1016/j.cnur.2004.09.002 · Cited by 122 · see citing works
Ectopic localization of matrix metalloproteinase-9 in chronic cutaneous wounds
Mirastschijski, U., Impola, U., Jahkola, T., Karlsmark, T., Ågren, M. S., & Saarialho‐Kere, U. (2002) · Human Pathology · doi:10.1053/hupa.2002.32221 · Cited by 103 · see citing works
Self-citationMARCHENKO, G. N., Ratnikov, B. I., Rozanov, D. V., et al. (2001) · Biochemical Journal · doi:10.1042/bj3560705 · Cited by 101 · see citing works
Inflammation. A Review of the Process
Trowbridge, H. O., Emling, R. C., & Fornatora, M. L. (1997) · Implant Dentistry · doi:10.1097/00008505-199700630-00025 · Cited by 99 · see citing works
MMP‐Mediated Events in Diabetes
RYAN, M. E., RAMAMURTHY, N. S., Sorsa, T. A., & Golub, L. M. (1999) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1999.tb07692.x · Cited by 99 · see citing works
Self-citationMarchenko, N. D., Marchenko, G. N., Weinreb, R. N., Lindsey, J. D., Kyshtoobayeva, A. S., Crawford, H. C., & Strongin, A. Y. (2004) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2003.12.007 · Cited by 98 · see citing works
Zhao, Y., Xiao, A., Park, H. I., Newcomer, R. G., Mei, Y., Man, Y., Heffelfinger, S. C., & Sang, Q. A. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-1932 · Cited by 97 · see citing works
Bister, V., Salmela, M. T., Karjalainen‐Lindsberg, M., et al. (2004) · Digestive Diseases and Sciences · doi:10.1023/b:ddas.0000026314.12474.17 · Cited by 94 · see citing works
Epidermal Development and Wound Healing in Matrix Metalloproteinase 13-Deficient Mice
Hartenstein, B., Dittrich, B. T., Stickens, D., Heyer, B. S., Vu, T. H., Teurich, S., Schorpp‐Kistner, M., Werb, Z., & Angel, P. E. (2005) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700084 · Cited by 93 · see citing works
Impola, U., Jeskanen, L., Ravanti, L., Syrjänen, S., Baldursson, B. T., Kähäri, V., & Saarialho‐Kere, U. (2005) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2005.06447.x · Cited by 90 · see citing works
Self-citationExpression and regulation of collagenase‐2 (MMP‐8) in head and neck squamous cell carcinomas
Moilanen, M., Pirilä, E., Grenman, R. A., Sorsa, T. A., & Salo, T. A. (2002) · The Journal of Pathology · doi:10.1002/path.1078 · Cited by 86 · see citing works
Self-citationPirilä, E., Ramamurthy, N., Maisi, P. S., McClain, S. A., Kucine, A. J., Wahlgren, J., Golub, L. M., Salo, T. A., & Sorsa, T. A. (2001) · Current Medicinal Chemistry · doi:10.2174/0929867013373552 · Cited by 82 · see citing works
Self-citationVaalamo, M., Weckroth, M., Puolakkainen, P. A., et al. (1996) · British Journal of Dermatology · doi:10.1046/j.1365-2133.1996.d01-932.x · Cited by 80 · see citing works
Ahokas, K., Skoog, T., Suomela, S., Jeskanen, L., Impola, U., Isaka, K., & Saarialho‐Kere, U. (2005) · Journal of Investigative Dermatology · doi:10.1111/j.0022-202x.2005.23640.x · Cited by 71 · see citing works
Self-citationLi, W., Savinov, A. Y., Rozanov, D. V., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-3019 · Cited by 57 · see citing works
Matrix metalloproteinase‐26 is expressed in human endometrium but not in endometrial carcinoma
Isaka, K., Nishi, H., Nakai, H., et al. (2002) · Cancer · doi:10.1002/cncr.11030 · Cited by 51 · see citing works
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Ellis, S., Lin, E. J., & Tartar, D. (2018) · Current Dermatology Reports · doi:10.1007/s13671-018-0234-9 · Cited by 625 · see citing works
Neutrophils and Wound Repair: Positive Actions and Negative Reactions
Wilgus, T. A., Roy, S., & McDaniel, J. C. (2013) · Advances in Wound Care · doi:10.1089/wound.2012.0383 · Cited by 616 · see citing works
- Authors
- Pirilä, E., Korpi, J. T., Korkiamäki, T., Jahkola, T., Gutierrez‐Fernandez, A., Lopez‐Otin, C., Saarialho‐Kere, U., Salo, T., & Sorsa, T.
- Affiliations
- University of Oulu (FI)
- Helsinki University Hospital (FI)
- University of Helsinki (FI)
- Venue
- Wound Repair and Regeneration
- Publisher
- Wiley
- Published
- 2007-01
- Volume
- 15
- Issue
- 1
- Pages
- 47-57
- ISSN
- 1067-1927 (ISSN-L)
- 1524-475X
- OpenAlex
- W2142036444
- Cited by
- 92
- References
- 43
- Citations by year
- 2025: 1 · 2024: 6 · 2023: 3 · 2022: 3 · 2021: 2 · 2020: 2 · 2019: 5 · 2018: 5 · 2017: 6 · 2016: 8 · 2015: 5 · 2014: 6 · 2013: 7 · 2012: 6
- FWCI
- 7.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Wound Repair and Regeneration (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Helsingin ja Uudenmaan Sairaanhoitopiiri
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Macrophage Migration Inhibitory Factor
- Keywords
- MMP-8, MMP-26, matrix metalloproteinases, wound healing, chronic wounds, acute wounds, keratinocyte migration, keratinocyte proliferation, basement membrane, neutrophils, epithelial cells, extracellular matrix
- MeSH terms
- Acute Disease, Aged, Aged, 80 and over, Chronic Disease, Female, Humans, Male, Middle Aged, Skin Ulcer, Varicose Ulcer, Vasculitis, Wound Healing, Matrix Metalloproteinase 8, Diabetes Complications, Matrix Metalloproteinases, Secreted
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