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MMP-8 Is the Predominant Collagenase in Healing Wounds and Nonhealing Ulcers
Abstract
Background The initial cleavage of collagen by collagenase represents the rate-limiting step in the degradation of this central extracellular matrix protein. Chronic nonhealing ulcers, especially pressure ulcers, typically contain elevated levels of collagenolytic activity. However, there have been no detailed attempts to identify the source of these collagenases and their activity either in normal healing wounds or in chronic nonhealing ulcers.Materials and methods Levels of the matrix metalloproteinases, MMP-1 and MMP-8, and the tissue inhibitor of matrix metalloproteinases, TIMP-1, were measured in fluids and tissues of healing human wounds and nonhealing ulcers by ELISA. Relative MMP-1 and MMP-8 levels were also analyzed by substrate preference in a functional assay.Results The patterns of the collagenases MMP-1 and MMP-8 in healing wounds were distinct, with MMP-8 appearing in significantly greater amounts than MMP-1. Chronic nonhealing ulcers were characterized by significantly higher levels of MMP-1 and MMP-8, and lower levels of TIMP-1, than in healing wounds. Levels of both MMP-1 and MMP-8 varied greatly in chronic ulcers, although MMP-8 was always the predominant collagenase present in these wounds. Interestingly, these collagenases were present almost exclusively in their inactive forms in healing wounds, whereas nonhealing ulcers possessed significant levels of the active forms of these enzymes.Conclusions These results clearly demonstrate that the neutrophil-derived MMP-8 is the predominant collagenase present in normal healing wounds and suggest that overexpression and activation of this collagenase may be involved in the pathogenesis of nonhealing chronic ulcers. In addition, excessive collagenolytic activity in chronic ulcers is made possible, partly because of the reduced levels of the inhibitor, TIMP-1.
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“Specifically, MMP‐1 and MMP‐8 are important, as they have been found to be active during wound healing and remodeling.”
From Unraveling and Harnessing the Immune Response at the Cell–Biomaterial Interface for Tissue Engineering Purposes (2024) · cites this paper as [257]
In the citing paper
“Both are used in the cleavage of collagen, with MMP‐1 being more proficient in the cleavage of collagen type III, while MMP‐8 is more efficient in degrading collagen type I and is the main collagenase active in regular healing.”
From Unraveling and Harnessing the Immune Response at the Cell–Biomaterial Interface for Tissue Engineering Purposes (2024) · cites this paper as [257]
In the citing paper
“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 [55]
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Wound healing: an overview of acute, fibrotic and delayed healing
Diegelmann, R. (2004) · Frontiers in Bioscience · doi:10.2741/1184 · Cited by 2,147
“The neutrophils release significant amounts of enzymes such as collagenase (matrix metalloproteinase8) that is responsible for destruction of the connective tissue matrix (57, 58).”
BackgroundAdvanced Therapeutic Dressings for Effective Wound Healing—A Review
Boateng, J. S., & Catanzano, O. (2015) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.24610 · Cited by 983
Concise Review: Role of Mesenchymal Stem Cells in Wound Repair
Maxson, S., Lopez, E. A., Yoo, D. S., Danilkovitch‐Miagkova, A., & LeRoux, M. A. (2012) · Stem Cells Translational Medicine · doi:10.5966/sctm.2011-0018 · Cited by 830
Oxygen in acute and chronic wound healing
Schreml, S., Szeimies, R., Prantl, L., Karrer, S., Landthaler, M., & Babilas, P. (2010) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2010.09804.x · Cited by 817
Menke, N. B., Ward, K. R., Witten, T. M., Bonchev, D. G., & Diegelmann, R. F. (2007) · Clinics in Dermatology · doi:10.1016/j.clindermatol.2006.12.005 · Cited by 792
Re-epithelialization of adult skin wounds: Cellular mechanisms and therapeutic strategies
Rousselle, P., Braye, F., & Dayan, G. (2018) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2018.06.019 · Cited by 679
“In chronic wounds, protease levels exceed that of their respective inhibitors, leading to destruction of the ECM and degradation of growth factors and their receptors [123-125].”
BackgroundThe molecular biology of chronic wounds and delayed healing in diabetes
Blakytny, R., & Jude, E. (2006) · Diabetic Medicine · doi:10.1111/j.1464-5491.2006.01773.x · Cited by 632
Ellis, S., Lin, E. J., & Tartar, D. (2018) · Current Dermatology Reports · doi:10.1007/s13671-018-0234-9 · Cited by 625
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
Lobmann, R., Ambrosch, A., Schultz, G. S., Waldmann, K., Schiweck, S., & Lehnert, H. (2002) · Diabetologia · doi:10.1007/s00125-002-0868-8 · Cited by 628
“Accordingly the expression of TIMPs by keratinocytes is reduced in chronic wounds [28, 42, 43].”
BackgroundProteases and Delayed Wound Healing
McCarty, S. M., & Percival, S. L. (2013) · Advances in Wound Care · doi:10.1089/wound.2012.0370 · Cited by 498
“In comparison, MMP-8 has been shown to be an important collagenase in the nonhealing wound; Nwomeh et al.37 demonstrated an elevated level of active MMP-8 in chronic wound fluids compared with acute wound fluids.”
InfluentialThe proteolytic environment of chronic wounds
Yager, D. R., & Nwomeh, B. C. (1999) · Wound Repair and Regeneration · doi:10.1046/j.1524-475x.1999.00433.x · Cited by 399
Self-citationMostow, E. N., Haraway, G. D., Dalsing, M. C., Hodde, J. P., & King, D. W. (2005) · Journal of Vascular Surgery · doi:10.1016/j.jvs.2005.01.042 · Cited by 387
LADWIG, G. P., Robson, M. C., Liu, R., Kuhn, M. A., Muir, D., & Schultz, G. S. (2002) · Wound Repair and Regeneration · doi:10.1046/j.1524-475x.2002.10903.x · Cited by 355
The Role of Matrix Metalloproteinases in Wound Healing
Armstrong, D. G., & Jude, E. B. (2002) · Journal of the American Podiatric Medical Association · doi:10.7547/87507315-92-1-12 · Cited by 347
Foot ulcers in the diabetic patient, prevention and treatment.
Wu, S., Driver, V. R., Wrobel, J. S., & Armstrong, D. G. (2007) · PubMed Central · Cited by 335
Saleh, B., Dhaliwal, H. K., Lara, R. P., Sani, E. S., Abdi, R., Amiji, M. M., & Annabi, N. (2019) · Small · doi:10.1002/smll.201902232 · Cited by 326
Raffetto, J. D., Ligi, D., Maniscalco, R., Khalil, R. A., & Mannello, F. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm10010029 · Cited by 356
Muller, M., Trocmé, C., Lardy, B., Morel, F., Halimi, S., & Benhamou, P. (2008) · Diabetic Medicine · doi:10.1111/j.1464-5491.2008.02414.x · Cited by 316
Attinger, C. E., Janis, J. E., Steinberg, J. S., Schwartz, J. S., Alattar, A. A., & Couch, K. S. (2006) · Plastic & Reconstructive Surgery · doi:10.1097/01.prs.0000225470.42514.8f · Cited by 294
A Dual‐Cross‐Linked Hydrogel Patch for Promoting Diabetic Wound Healing
Liu, J., Qu, M., Wang, C., Xue, Y., Huang, H., Chen, Q., Sun, W., Zhou, X., Xu, G., & Jiang, X. (2022) · Small · doi:10.1002/smll.202106172 · Cited by 290
Increased inflammation delays wound healing in mice deficient in collagenase‐2 (MMP‐8)
Gutiérrez‐Fernández, A., Inada, M., Balbı́n, M., Fueyo, A., Pitiot, A. S., Astudillo, A., Hirose, K., Hirata, M., Shapiro, S. D., Noël, A., et al. (2007) · The FASEB Journal · doi:10.1096/fj.06-7860com · Cited by 289
CULLEN, B., Smith, R., McCulloch, E., Silcock, D., & Morrison, L. (2002) · Wound Repair and Regeneration · doi:10.1046/j.1524-475x.2002.10703.x · Cited by 273
Engineered Nanomaterials for Infection Control and Healing Acute and Chronic Wounds
Parani, M., Lokhande, G. K., Singh, A. K., & Gaharwar, A. K. (2016) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.6b00291 · Cited by 269
Owen, 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
“In addition, MMP-8 has been implicated in the pathogenesis of several chronic inflammatory diseases characterized by excessive influx and activation of polymorphonuclear cell (PMN), including cystic fibrosis (6), rheumatoid arthritis (7), periodontal disease (8), and chronic skin wounds (9).”
BackgroundMatrix metalloproteinases and epidermal wound repair
Martins, V., Caley, M. P., & O’Toole, E. A. (2012) · Cell and Tissue Research · doi:10.1007/s00441-012-1410-z · Cited by 261
“Wound fluid of chronic ulcers shows increased levels of MMPs such as MMP-1, -2, -8 and -9 (Nwomeh et al. 1999; Wysocki et al. 1993; Yager et al. 1996), as well as increased activity of the gelatinases MMP-2 and -9 (Bullen et al. 1995; Widgerow 2011).”
BackgroundSbardella, D., Fasciglione, G. F., Gioia, M., Ciaccio, C., Tundo, G. R., Marini, S., & Coletta, M. (2011) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2011.10.015 · Cited by 251
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Oxidative stress in chronic venous leg ulcers
Wlaschek, M., & Scharffetter‐Kochanek, K. (2005) · Wound Repair and Regeneration · doi:10.1111/j.1067-1927.2005.00065.x · Cited by 241
Matrix metalloproteinase-8: Cleavage can be decisive
VANLINT, P., & Libert, C. (2006) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2006.04.001 · Cited by 238
“However, activated MMP-8 is more prominent in chronic than in healing wounds [29], a difference that was linked to the large number of neutrophils present in chronic wounds [30].”
BackgroundThe innate immune system, toll-like receptors and dermal wound healing: A review
Portou, M. J., Baker, D., Abraham, D., & Tsui, J. C. S. (2015) · Vascular Pharmacology · doi:10.1016/j.vph.2015.02.007 · Cited by 233
“Neutrophils in particular appear to contribute to these destructive wound conditions through upregulated release of MMP-8 and downregulated release of the MMP inhibitor TIMP1 in chronic wounds [54].”
BackgroundRegular debridement is the main tool for maintaining a healthy wound bed in most chronic wounds
Wolcott, R. D., Kennedy, J. P., & Dowd, S. E. (2009) · Journal of Wound Care · doi:10.12968/jowc.2009.18.2.38743 · Cited by 218
Effects of Hydrogen Peroxide on Wound Healing in Mice in Relation to Oxidative Damage
Loo, A. E. K., Wong, Y. T., Ho, R., Wasser, M., Du, T., Ng, W. T., & Halliwell, B. B. (2012) · PLoS ONE · doi:10.1371/journal.pone.0049215 · Cited by 216
“MMP-8 is the predominant collagenase in acute wounds and chronic wounds [32] while MMP-9 is the most abundant gelatinase in chronic wounds [31].”
BackgroundPathophysiology 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 205
Proteases and the Diabetic Foot Syndrome: Mechanisms and Therapeutic Implications
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“For example, the expression of MMP-1 is typically associated with the migra t ion o f ke ra t inocy t e s (24,56,57).”
BackgroundProteinases in cutaneous wound healing
Toriseva, M., & Kähäri, V. (2008) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-008-8388-4 · Cited by 220
Gottrup, F., Ågren, M. S., & Karlsmark, T. (2000) · Wound Repair and Regeneration · doi:10.1046/j.1524-475x.2000.00083.x · Cited by 199
Gabriel, A., Shores, J. T., Heinrich, C. A., et al. (2008) · International Wound Journal · doi:10.1111/j.1742-481x.2007.00423.x · Cited by 198
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Acosta, J. B., del Barco, D. G., Cibrián, D., Savigne, W., López-Saura, P. A., Nieto, G. G., & Schultz, G. S. (2008) · International Wound Journal · doi:10.1111/j.1742-481x.2008.00457.x · Cited by 192
Proteases and pH in chronic wounds
Greener, B., Hughes, A., Bannister, N. P., & Douglass, J. (2005) · Journal of Wound Care · doi:10.12968/jowc.2005.14.2.26739 · Cited by 189
Cullen, B., Watt, P. W., Lundqvist, C., Silcock, D., Schmidt, R. J., Bogan, D. P., & Light, N. D. (2002) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(02)00054-7 · Cited by 190
Lazaro, J. L., Izzo, V., Meaume, S., Davies, A. H., Lobmann, R., & Uccioli, L. (2016) · Journal of Wound Care · doi:10.12968/jowc.2016.25.5.277 · Cited by 185
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BackgroundClinical implications of matrix metalloproteinases
Mandal, M., Mandal, A., Das, S. K., Chakraborti, T., & Chakraborti, S. (2003) · Molecular and Cellular Biochemistry · doi:10.1023/a:1025526424637 · Cited by 173
Reduction of scar formation in full‐thickness wounds with topical celecoxib treatment
Wilgus, T. A., Vodovotz, Y., Vittadini, E., Clubbs, E. A., & Oberyszyn, T. M. (2003) · Wound Repair and Regeneration · doi:10.1046/j.1524-475x.2003.11106.x · Cited by 168
Activity of mesenchymal stem cells in therapies for chronic skin wound healing
Nuschke, A. (2013) · Organogenesis · doi:10.4161/org.27405 · Cited by 173
Excessive neutrophils characterize chronic pressure ulcers
Diegelmann, R. F. (2003) · Wound Repair and Regeneration · doi:10.1046/j.1524-475x.2003.11617.x · Cited by 168
Matrix metalloproteinases and tissue inhibitor of metalloproteinase-1 in sarcoidosis and IPF
Henry, M. T., McMahon, K., Mackarel, A. J., Prikk, K., Sorsa, T. A., Maisi, P., Sepper, R., FitzGerald, M. X., & O'CONNOR, C. M. (2002) · European Respiratory Journal · doi:10.1183/09031936.02.00022302 · Cited by 163
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BackgroundNatarajan, V., Krithica, N., Madhan, B., & Sehgal, P. K. (2012) · Journal of Biomedical Materials Research Part B Applied Biomaterials · doi:10.1002/jbm.b.32856 · Cited by 161
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Rutkowski, J. M., Boardman, K. C., & Swartz, M. A. (2006) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00038.2006 · Cited by 159
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Xue, M., Le, N. T., & Jackson, C. (2006) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.10.1.143 · Cited by 153
“In contrast to their precise temporal and spatial expression in normal wound healing, MMP levels are markedly elevated in chronic ulcers [69-75,59].”
BackgroundWound healing and TIME; new concepts and scientific applications
Schultz, G. S., Mozingo, D. W., Romanelli, M., & Claxton, K. (2005) · Wound Repair and Regeneration · doi:10.1111/j.1067-1927.2005.1304s1.x · Cited by 152
Armstrong, D. G., Lavery, L. A., Nixon, B. P., & Boulton, A. J. M. (2004) · Clinical Infectious Diseases · doi:10.1086/383269 · Cited by 144
“portant as off-loading in reducing the prevalence of chronic inflammatory by-products in a wound [6–8] and, thus, in converting a chronic wound to an acute one [9].”
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Wong, T. T. L., Sethi, C. S., Daniels, J. T., Limb, G. A., Murphy, G., & Khaw, P. T. (2002) · Survey of Ophthalmology · doi:10.1016/s0039-6257(02)00287-4 · Cited by 140
Moseley, R., Stewart, J. E., Stephens, P., Waddington, R. J., & Thomas, D. W. (2004) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2004.05845.x · Cited by 127
Xue, M., Zhao, R., Lin, H., & Jackson, C. (2018) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2018.03.002 · Cited by 124
Overview: Acute and Chronic Wounds
Whitney, J. D. (2005) · Nursing Clinics of North America · doi:10.1016/j.cnur.2004.09.002 · Cited by 128
Hart, J., Silcock, D., Gunnigle, S., Cullen, B., Light, N. D., & Watt, P. W. (2002) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(02)00062-6 · Cited by 116
Predicting delayed pressure ulcer healing using thermography: a prospective cohort study
Nakagami, G., Sanada, H., Iizaka, S., Kadono, T., Higashino, T., Koyanagi, H., & Haga, N. (2010) · Journal of Wound Care · doi:10.12968/jowc.2010.19.11.79695 · Cited by 116
Schönfelder, U., Abel, M., Wiegand, C., Klemm, D., Elsner, P. U., & Hipler, U. (2005) · Biomaterials · doi:10.1016/j.biomaterials.2005.04.030 · Cited by 117
Toward a common language: surgical wound bed preparation and debridement
Granick, M. S., Boykin, J. V., Gamelli, R. L., Schultz, G. S., & Tenenhaus, M. (2006) · Wound Repair and Regeneration · doi:10.1111/j.1524-475x.2005.00096.x · Cited by 113
“Two groups of proteases in particular are elevated in chronic wounds: the matrix metalloproteinases, and the serine protease, elastase.(7,8) At the same time, the inhibitors of these proteases are suppressed, causing a cycle of further tissue damage, destruction of growth factors and other tissue proteins necessary fo…”
BackgroundToriseva, M., Laato, M. K., Carpén, O., Ruohonen, S. T., Savontaus, E., Inada, M., Krane, S. M., & Kähäri, V. (2012) · PLoS ONE · doi:10.1371/journal.pone.0042596 · Cited by 117
“Increased expression of MMP-8 (neutrophil collagenase) has been suggested to cover the lack of the proteolytic activity of MMP-13 in skin wound in MMP-13 deficient mice [27].”
BackgroundWong, T. T. L., Mead, A. L., & Khaw, P. T. (2003) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.02-0366 · Cited by 113
Wiegand, C., Schönfelder, U., Abel, M., et al. (2009) · Archives of Dermatological Research · doi:10.1007/s00403-009-1011-1 · Cited by 113
“In chronic wounds, a massive and constant inWltration of inXammatory cells has been shown [4, 47], which release a number of proteases [2, 24 ] and pro-inXammatory cytokines [3].”
BackgroundDonato-Trancoso, A., Monte-Alto-Costa, A., & Romana-Souza, B. (2016) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2016.03.012 · Cited by 112
“Pressure ulcers present a massive invasion of numerous neutrophils, and their destructive enzymes, leading to tissue destruction [12,13].”
BackgroundThe Role of Doxycycline as a Matrix Metalloproteinase Inhibitor for the Treatment of Chronic Wounds
Stechmiller, J. K., Cowan, L. J., & Schultz, G. S. (2009) · Biological Research For Nursing · doi:10.1177/1099800409346333 · Cited by 112
Proteinases, their inhibitors, and cytokine profiles in acute wound fluid
Baker, E. A., & Leaper, D. J. (2000) · Wound Repair and Regeneration · doi:10.1111/j.1524-475x.2000.00392.x · Cited by 116
Role of matrix metalloproteinases in non‐healing venous ulcers
Amato, B., Coretti, G., Compagna, R., et al. (2013) · International Wound Journal · doi:10.1111/iwj.12181 · Cited by 104
Wound Fluids: A Window Into the Wound Environment?
Yager, D. R., Kulina, R. A., & Gilman, L. A. (2007) · The International Journal of Lower Extremity Wounds · doi:10.1177/1534734607307035 · Cited by 108
“Evidence for the presence or expression of all 3 interstitial collagenases has been found in chronic wounds.(4,8,11,46,65,67) However, quantitatively, neutrophil collagenase is found in significantly higher levels than either MMP-1 or MMP-13 in both acute and chronic wounds.”
BackgroundSelf-citationHolopainen, J. M., Moilanen, J., Sorsa, T. A., Kivelä‐Rajamäki, M. J., Tervahartiala, T. I., Vesaluoma, M. H., & Tervo, T. (2003) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.02-1190 · Cited by 105
“Furthermore, expression of MMP-8 is also upregulated in wound healing and tissue remodeling.(52,53) Overexpression of MMP-8 has been attributed to nonhealing chronic ulcers(52) suggesting that corneal regulation of the activity of MMP-8 is important.”
BackgroundSyk, I., Ågren, M. S., Adawi, D., et al. (2001) · British journal of surgery · doi:10.1046/j.1365-2168.2001.01649.x · Cited by 101
Matrix metalloproteinase8 has a central role in inflammatory disorders and cancer progression
Dejonckheere, E., Vandenbroucke, R. E., & Libert, C. (2011) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2011.02.002 · Cited by 100
“chronic wounds in humans [99], especially in epithelial cells, neutrophils and other inflammatory cells [100].”
BackgroundSarkar, P. R., & Ballantyne, S. (2000) · Postgraduate Medical Journal · doi:10.1136/pmj.76.901.674 · Cited by 100
“MMP8 is the predominant collagenase in healing wounds and non-healing ulcers.”
BackgroundWall, S. J., Bevan, D., Thomas, D. W., Harding, K. G., Edwards, D. R., & Murphy, G. (2002) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.2002.01779.x · Cited by 100
Xu, L., Zhang, Z., Jorgensen, A. M., Yang, Y., Jin, Q., Zhang, G., Cao, G., Fu, Y., Zhao, W., Ju, J., et al. (2023) · Materials Today Bio · doi:10.1016/j.mtbio.2023.100550 · Cited by 101
“The main proteolytic enzyme involved in wound healing is type II collagenase (matrix metalloproteinase-8 [MMP-8]) [39].”
BackgroundTarget molecules for anti-angiogenic therapy: from basic research to clinical trials
Hagedorn, M., & Bikfalvi, A. (2000) · Critical Reviews in Oncology/Hematology · doi:10.1016/s1040-8428(00)00056-1 · Cited by 102
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Määttã, M., Kari, O., Tervahartiala, T. I., Peltonen, S., Kari, M., Saari, M., & Sorsa, T. A. (2006) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/s00417-005-0212-3 · Cited by 99
“Levels and activation of MMP-8 are upregulated in many inflammatory diseases, such as rheumatoid arthritis, bronchial asthma, periodontitis and non-healing chronic ulcers [17, 22, 25, 27] and is also actively secreted by inflammatory cells [44].”
Randomized controlled trial on collagen/oxidized regenerated cellulose/silver treatment
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O’Brien, T. P., Li, Q. J., Sauerburger, F., et al. (2001) · Ophthalmology · doi:10.1016/s0161-6420(00)00590-x · Cited by 95
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Collagenase‐2 (MMP‐8) and matrilysin‐2 (MMP‐26) expression in human wounds of different etiologies
Pirilä, E., Korpi, J. T., Korkiamäki, T., Jahkola, T., Gutierrez‐Fernandez, A., Lopez‐Otin, C., Saarialho‐Kere, U., Salo, T., & Sorsa, T. (2007) · Wound Repair and Regeneration · doi:10.1111/j.1524-475x.2006.00184.x · Cited by 92
“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…”
BackgroundImpola, 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
Stadlmann, S., Pollheimer, J., Moser, P. L., et al. (2003) · European Journal of Cancer · doi:10.1016/j.ejca.2003.08.011 · Cited by 89
Antioxidant, Wound Healing Potential and In Silico Assessment of Naringin, Eicosane and Octacosane
Balachandran, A., Choi, S. B., MORAK-MŁODAWSKA, B. I., Jeleń, M., Froemming, G. R. A., Lavilla, C. A., Billacura, M. P., Siyumbwa, S. N., & Okechukwu, P. N. (2023) · Molecules · doi:10.3390/molecules28031043 · Cited by 95
Roles of Matrix Metalloproteinases in Cutaneous Wound Healing
Nguyen, T. T., Mobashery, S., & Chang, M. (2016) · InTech eBooks · doi:10.5772/64611 · Cited by 97
“Once the cutaneous injury happens, up-regulation and expression of many MMPs have been reported, including collagenases (MMP-1 [83], MMP-8 [60, 61], and MMP-13 [70]), gelatinases (MMP-2 [51] and MMP-9 [51, 60]), stromelysins (MMP-3 and MMP-10 [54]), and other MMPs such as MMP-7 [58], MMP-12 [50], and MMP-14 [51].”
BackgroundInfluentialArul, V., Kartha, R., & Jayakumar, R. (2007) · Life Sciences · doi:10.1016/j.lfs.2006.09.018 · Cited by 85
The biological and physiological impact of the performance of wound dressings
Cullen, B., & Gefen, A. (2022) · International Wound Journal · doi:10.1111/iwj.13960 · Cited by 94
Li, W., Kandhare, A. D., Mukherjee-Kandhare, A. A., & Bodhankar, S. L. (2018) · EXCLI journal · doi:10.17179/excli2018-1036 · Cited by 91
“Abnormalities in the synthesis of this connective tissue protein at the wound area after an injury delays healing process (Nwomeh et al., 1999).”
Inflammation 2: its role in the healing of chronic wounds
Hart, J. (2002) · Journal of Wound Care · doi:10.12968/jowc.2002.11.7.26416 · Cited by 82
Oliva, N., & Almquist, B. D. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.07.021 · Cited by 81
Shi, L., & Ronfard, V. (2013) · Europe PMC (PubMed Central) · Cited by 97
CONSEQUENCES OF LONG-TERM INFLAMMATION
Homer, R., & Elias, J. A. (2000) · Clinics in Chest Medicine · doi:10.1016/s0272-5231(05)70270-7 · Cited by 77
Exosomal miRNA-26b-5p from PRP suppresses NETs by targeting MMP-8 to promote diabetic wound healing
Rui, S., Dai, L., Zhang, X., He, M. Y., Xu, F., Wu, W., Armstrong, D. G., You, Y., Xiao, X., Ma, Y., et al. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.06.050 · Cited by 79
Matrix metalloproteinase biology applied to vitreoretinal disorders
Sethi, C. S. (2000) · British Journal of Ophthalmology · doi:10.1136/bjo.84.6.654 · Cited by 75
Effect of enzymatic degradation on the mechanical properties of biological scaffold materials
Annor, A. H., Tang, M. E., Pui, C. L., Ebersole, G. C., Frisella, M. M., Matthews, B. D., & Deeken, C. R. (2012) · Surgical Endoscopy · doi:10.1007/s00464-012-2277-5 · Cited by 76
“Collagenases such as MMP-1 and MMP-8 are commonly detected in healing wounds [12].”
BackgroundOrchestrating Wound Healing: Assessing and Preparing the Wound Bed
Hess, C. T., & Kirsner, R. S. (2003) · Advances in Skin & Wound Care · doi:10.1097/00129334-200309000-00015 · Cited by 74
Metalloproteinases in chronic and acute wounds: A systematic review and meta‐analysis
Tardáguila‐García, A., García‐Morales, E., Garcia-Alamino, J. M., Álvaro‐Afonso, F. J., Molines-Barroso, R. J., & Lázaro‐Martínez, J. L. (2019) · Wound Repair and Regeneration · doi:10.1111/wrr.12717 · Cited by 75
Metadata
- Authors
- Nwomeh, B. C., Liang, H.-X., Cohen, I. K., & Yager, D. R.
- Affiliations
- Virginia Commonwealth University (US)
- ORCID
- Nwomeh, Benedict C.
- Venue
- Journal of Surgical Research
- Publisher
- Elsevier BV
- Published
- 1999-02
- Volume
- 81
- Issue
- 2
- Pages
- 189-195
- ISSN
- 0022-4804 (ISSN-L)
- OpenAlex
- W1988325190
- Cited by
- 357
- References
- 0
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 14 · 2023: 8 · 2022: 8 · 2021: 11 · 2020: 13 · 2019: 10 · 2018: 18 · 2017: 18 · 2016: 18 · 2015: 14 · 2014: 9 · 2013: 15 · 2012: 20
- FWCI
- 12.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Surgical Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (GM20298)
- Topics
- Health Sciences › Medicine › Surgery › Wound Healing and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pineapple and bromelain studies
- Keywords
- MMP-8, MMP-1, TIMP-1, collagenase, wound healing, chronic non-healing ulcers, pressure ulcers, collagen degradation, extracellular matrix, neutrophils, matrix metalloproteinases, collagenolytic activity
- MeSH terms
- Adult, Chronic Disease, Pressure Ulcer, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Mastectomy, Middle Aged, Skin, Surgical Flaps, Time Factors, Varicose Ulcer, Wound Healing, Wounds and Injuries, Collagenases, Tissue Inhibitor of Metalloproteinase-1, Matrix Metalloproteinase 1, Matrix Metalloproteinase 8
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