Potential role of metalloproteinase inhibitors from radiation‑sterilized amnion dressings in the healing of venous leg ulcers

Litwiniuk,Małgorzata; Bikowska,Barbara; Niderla-Bielińska,Justyna; Jóźwiak,Jarosław; Kamiński,Artur; Skopiński,Piotr; Grzela,Tomasz

doi:10.3892/mmr.2012.983

Potential role of metalloproteinase inhibitors from radiation‑sterilized amnion dressings in the healing of venous leg ulcers

Authors:
- Małgorzata Litwiniuk
- Barbara Bikowska
- Justyna Niderla-Bielińska
- Jarosław Jóźwiak
- Artur Kamiński
- Piotr Skopiński
- Tomasz Grzela
View Affiliations

Affiliations: Department of Histology and Embryology, Warsaw Medical University, Warsaw, Poland, Department of Transplantology and Central Tissue Bank, Warsaw Medical University, Warsaw, Poland, 2nd Department of Ophthalmology, Warsaw Medical University, Warsaw, Poland
Published online on: July 11, 2012 https://doi.org/10.3892/mmr.2012.983
Pages: 723-728

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Chronic wounds are a significant socio-economic problem, thus, the improvement of the effectiveness of their treatment is an important objective for public health strategies. The predominant stage of the chronic wound is the inflammatory reaction which is associated with the damage of tissues, possibly due to the excessive secretion and activation of matrix metalloproteinases (MMPs). Several reports have suggested that amnion dressing inhibits tissue destruction and accelerates wound healing. Our recent study revealed that sterilized amnion stimulates keratinocyte proliferation in vitro, while the present study focused on the clinical application of radiation-sterilized amnion in chronic venous leg ulcers and aimed to explain the possible mechanism of its in vivo action. The study involved 25 individuals suffering from venous leg ulceration with a surface area of 10-100 cm2 and a healing rate below 10% per week, as verified during a 2-week screening period. The effectiveness of the amnion dressing was estimated following 4 weeks of treatment. The wound assessment, based on a modified Bates-Jensen Questionnaire, revealed a good and satisfactory response to the treatment in 23 of the 25 patients. The measurement of MMP-2 and MMP-9 activities in wound exudates revealed a decrease in activity in response to amnion application. This effect resulted from the presence of the potent MMP inhibitors, tissue inhibitor of metalloproteinases-1 (TIMP-1), type-1 plasminogen activator inhibitor (PAI-1) and thrombospondin-1 (TSP-1) in the amnion dressings, as shown by real-time fluorescence zymography and protein microarrays. Thus, unlike modern synthetic dressing materials, radiation-sterilized amnion dressings may have a multidirectional beneficial effect on chronic wounds.

View Figures

View References

1	MacKenzie RK, Brown DA, Allan PL, Bradbury AW and Ruckley CV: A comparison of patients who developed venous leg ulceration before and after their 50th birthday. Eur J Vasc Endovasc Surg. 26:176–178. 2003. View Article : Google Scholar : PubMed/NCBI
2	Mustoe TA, O’Shaughnessy K and Kloeters O: Chronic wound pathogenesis and current treatment strategies: a unifying hypothesis. Plast Reconstr Surg. 117:S35–S41. 2006. View Article : Google Scholar : PubMed/NCBI
3	Litwiniuk M, Grzela T and Brawura-Biskupski-Samaha R: Clinical Immunology: Chronic inflammation in venous leg ulcer - problems and perspectives. Centr Eur J Immunol. 34:247–251. 2009.
4	Tauzin H, Humbert P, Viennet C, Saas P and Muret P: Human amniotic membrane in the management of chronic venous leg ulcers. Ann Dermatol Venereol. 138:572–579. 2011.PubMed/NCBI
5	Litwiniuk M, Bikowska B, Niderla-Bielińska J, JóŸwiak J, Kamiński A, Skopiński P and Grzela T: High molecular weight hyaluronan and stroma-embedded factors of radiation-sterilized amniotic membrane stimulate proliferation of HaCaT cell line in vitro. Centr Eur J Immunol. 36:205–211. 2011.
6	Jiang D, Liang J and Noble PW: Hyaluronan in tissue injury and repair. Ann Rev Cell Dev Biol. 23:435–461. 2007. View Article : Google Scholar : PubMed/NCBI
7	Wolbank S, Hildner F, Redl H, van Griensven M, Gabriel C and Hennerbichler S: Impact of human amniotic membrane preparation on release of angiogenic factors. J Tissue Eng Regen Med. 3:651–654. 2009. View Article : Google Scholar : PubMed/NCBI
8	Russo A and Bonci P and Bonci P: The effects of different preservation processes on the total protein and growth factor content in a new biological product developed from human amniotic membrane. Cell Tissue Bank. 13:353–361. 2012. View Article : Google Scholar
9	Tyszkiewicz JT, Uhrynowska-Tyszkiewicz IA, Kaminski A and Dziedzic-Goclawska A: Amnion allografts prepared in the Central Tissue Bank in Warsaw. Ann Transplant. 4:85–90. 1999.PubMed/NCBI
10	Grzela T, Brawura-Biskupski-Samaha R, Jelenska MM and Szmidt J: Low molecular weight heparin treatment decreases MMP-9 plasma activity in patients with abdominal aortic aneurysm. Eur J Vasc Endovasc Surg. 35:159–161. 2008. View Article : Google Scholar : PubMed/NCBI
11	Niknejad H, Peirovi H, Jorjani M, Ahmadiani A, Ghanavi J and Seifalian AM: Properties of the amniotic membrane for potential use in tissue engineering. Eur Cell Mater. 15:88–99. 2008.PubMed/NCBI
12	Chem PL, Baum CL and Arpey CJ: Biologic dressings: current applications and limitations in dermatologic surgery. Dermatol Surg. 35:891–906. 2009. View Article : Google Scholar : PubMed/NCBI
13	Bjarnsholt T, Kirketerp-Moller, Jensen P, et al: Why chronic wounds will not heal: a novel hypothesis. Wound Repair Regen. 16:2–10. 2008. View Article : Google Scholar : PubMed/NCBI
14	Rayment EA, Upton Z and Shooter GK: Increased matrix metalloproteinase-9 (MMP-9) activity observed in chronic wound fluid is related to the clinical severity of the ulcer. Br J Dermatol. 158:951–961. 2008. View Article : Google Scholar : PubMed/NCBI
15	Wysocki AB, Kusakabe AO, Chang S and Tuan TL: Temporal expression of urokinase plasminogen activator, plasminogen activator inhibitor and gelatinase-B in chronic wound fluid switches from a chronic to acute wound profile with progression to healing. Wound Rep Reg. 7:154–165. 1999. View Article : Google Scholar
16	Saito S, Trovato MJ, You R, et al: Role of matrix metalloproteinases 1, 2, and 9 and tissue inhibitor of matrix metalloproteinase-1 in chronic venous insufficiency. J Vasc Surg. 34:930–938. 2001. View Article : Google Scholar : PubMed/NCBI
17	Grzela T, Bikowska B and Litwiniuk M: Matrix metalloproteinases in aortic aneurysm - executors or executioners? Etiology, Pathogenesis and Pathophysiology of Aortic Aneurysms and Aneurysm Rupture. Grundmann R: Intech Publ; pp. 25–54. 2011, Available from: http://www.intechopen.com/articles/show/title/matrix-metalloproteinases-in-aortic-aneurysm-executors-or-executioners-.
18	Fu X, Parks WC and Heinecke JW: Activation and silencing of matrix metalloproteinases. Semin Cell Dev Biol. 19:2–13. 2008. View Article : Google Scholar : PubMed/NCBI
19	Suzuki K, Nakayama H and Doi K: Kinetics of matrix metalloproteinases and their regulatory factors in mercuric chloride-induced tubulointerstitial fibrosis in Brown Norway rats. Exp Toxic Pathol. 53:337–343. 2001. View Article : Google Scholar
20	Duffy M: The urokinase plasminogen activator system: role in malignancy. Curr Pharm Des. 10:39–49. 2004. View Article : Google Scholar : PubMed/NCBI
21	Bein K and Simons M: Thrombospondin type 1 repeats interact with matrix metalloproteinase 2. Regulation of metalloproteinase activity. J Biol Chem. 275:32167–32173. 2000. View Article : Google Scholar : PubMed/NCBI