Topical synthetic inhibitor of matrix metalloproteinases delays epidermal regeneration of human wounds
- PMID: 11589731
- DOI: 10.1034/j.1600-0625.2001.100506.x
Topical synthetic inhibitor of matrix metalloproteinases delays epidermal regeneration of human wounds
Abstract
Matrix metalloproteinases (MMPs) degrade extracellular proteins during epithelialization of wounds. To evaluate the biological significance of MMPs in epidermal healing, the synthetic broad-spectrum MMP inhibitor GM 6001 (also called Galardin and Ilomastat) was applied topically to standardized human wounds. GM 6001 (10 microg/microl) or vehicle alone was applied every second day onto 4 de-roofed 6 mm suction blister wounds on the volar forearm of healthy male volunteers for 12 days. GM 6001 delayed healing by 2-4 days as assessed macroscopically and microscopically. In situ hybridization or immunohistochemistry showed that MMP-1 (interstitial collagenase) was present in and MMP-2 (gelatinase A) close to laterally migrating keratinocytes whereas MMP-9 (gelatinase B) was seen during maturation of new epidermis. MMP-1 was undetectable in blister roofs (normal epidermis) and found in low levels in normal skin. Total MMP-1 activities increased about 100-fold in wounds, independent of treatment, compared to normal skin as analyzed by specific ELISA-based activity assay. By gelatin zymography, MMP-2, but not MMP-9, was detected in blister roofs and wound healing was associated with increased active MMP-2 and latent MMP-9 levels. GM 6001 prevented activation of MMP-2 and increased latent MMP-9 levels. GM 6001 delayed re-appearance of laminin-5, the synthesis of which correlated with epidermal regeneration. Restoration of stratum corneum, measured indirectly by transepidermal water loss, was also impaired (P<0.05) in the GM 6001 group. In conclusion, pharmacological MMP inhibition delayed epidermal regeneration in vivo, suggesting that MMPs are required to restore epidermis after epidermal ablation in humans.
Similar articles
-
Effect of smoking, abstention, and nicotine patch on epidermal healing and collagenase in skin transudate.Wound Repair Regen. 2009 May-Jun;17(3):347-53. doi: 10.1111/j.1524-475X.2009.00479.x. Wound Repair Regen. 2009. PMID: 19660042 Clinical Trial.
-
Salvianolic acid B in vitro inhibited matrix metalloproteinases-1, -2, and -9 activities.Zhong Xi Yi Jie He Xue Bao. 2009 Feb;7(2):145-50. doi: 10.3736/jcim20090210. Zhong Xi Yi Jie He Xue Bao. 2009. PMID: 19216858
-
Matrix metalloproteinase inhibitor BB-3103 unlike the serine proteinase inhibitor aprotinin abrogates epidermal healing of human skin wounds ex vivo.J Invest Dermatol. 2002 Jan;118(1):55-64. doi: 10.1046/j.0022-202x.2001.01652.x. J Invest Dermatol. 2002. PMID: 11851876
-
Role of matrix metalloproteinases and their inhibition in cutaneous wound healing and allergic contact hypersensitivity.Ann N Y Acad Sci. 1999 Jun 30;878:12-24. doi: 10.1111/j.1749-6632.1999.tb07671.x. Ann N Y Acad Sci. 1999. PMID: 10415717 Review.
-
Patterns of matrix metalloproteinase and TIMP expression in chronic ulcers.Arch Dermatol Res. 1998 Jul;290 Suppl:S47-54. doi: 10.1007/pl00007453. Arch Dermatol Res. 1998. PMID: 9710383 Review.
Cited by
-
Targeting Macrophages: Therapeutic Approaches in Diabetic Kidney Disease.Int J Mol Sci. 2024 Apr 15;25(8):4350. doi: 10.3390/ijms25084350. Int J Mol Sci. 2024. PMID: 38673935 Free PMC article. Review.
-
Gene Expression Linked to Reepithelialization of Human Skin Wounds.Int J Mol Sci. 2022 Dec 12;23(24):15746. doi: 10.3390/ijms232415746. Int J Mol Sci. 2022. PMID: 36555389 Free PMC article.
-
Role of matrix metalloproteinases in diabetic foot ulcers: Potential therapeutic targets.Front Pharmacol. 2022 Oct 20;13:1050630. doi: 10.3389/fphar.2022.1050630. eCollection 2022. Front Pharmacol. 2022. PMID: 36339630 Free PMC article. Review.
-
Biomarkers of Skin Graft Healing in Venous Leg Ulcers.Acta Derm Venereol. 2022 Jul 7;102:adv00749. doi: 10.2340/actadv.v102.201. Acta Derm Venereol. 2022. PMID: 35604238 Free PMC article.
-
Effect of Stabilized Hypochlorous Acid on Re-epithelialization and Bacterial Bioburden in Acute Wounds: A Randomized Controlled Trial in Healthy Volunteers.Acta Derm Venereol. 2022 May 31;102:adv00727. doi: 10.2340/actadv.v102.1624. Acta Derm Venereol. 2022. PMID: 35578822 Free PMC article. Clinical Trial.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous