Production and activation of matrix metalloproteinase-2 in proliferative diabetic retinopathy - PubMed (original) (raw)
. 2003 May;44(5):2163-70.
doi: 10.1167/iovs.02-0662.
Affiliations
- PMID: 12714657
- DOI: 10.1167/iovs.02-0662
Production and activation of matrix metalloproteinase-2 in proliferative diabetic retinopathy
Kousuke Noda et al. Invest Ophthalmol Vis Sci. 2003 May.
Abstract
Purpose: To investigate the matrix metalloproteinase (MMP) species and their activation associated with the pathogenesis of proliferative diabetic retinopathy (PDR).
Methods: Sandwich enzyme immunoassays were used to measure concentrations of MMP-1, -2, -3, -7, -8, -9, and -13 in vitreous samples from patients with PDR and nondiabetic vitreoretinal diseases. To evaluate activation ratios of the zymogen of MMP-2 (proMMP-2) and -9 (proMMP-9) in the vitreous samples and fibrovascular tissues, gelatin zymography was performed. Production and tissue localization of MMP-2, membrane type 1-MMP (MT1-MMP), tissue inhibitor of metalloproteinases (TIMP)-2, and MMP-9 in the fibrovascular tissues were examined by immunohistochemistry. mRNA expression of MT1-MMP in the tissues was determined by reverse transcription-polymerase chain reaction (RT-PCR).
Results: Among the seven different MMPs examined in the vitreous samples, only the levels of MMP-2 and -9 were significantly higher in the PDR samples than in the control. However, activation ratios of proMMP-2 (10.6% +/- 11.8%) and proMMP-9 (2.5% +/- 5.1%) in PDR vitreous samples were low and not significantly different from those of the control. In contrast, high activation ratios of proMMP-2 (54.3% +/- 13.6%) and notable activation of proMMP-9 (19.5% +/- 7.8%) were observed in the fibrovascular tissues. Immunohistochemical study demonstrated the localization of MMP-2 and -9 in the endothelial cells and glial cells of the fibrovascular tissues. MMP-2 was colocalized with MT1-MMP and TIMP-2, which are an activator and an activation-enhancing factor, respectively, for proMMP-2. RT-PCR analysis indicated the gene expression of MT1-MMP in the tissues.
Conclusions: These data demonstrate that proMMP-2 is efficiently activated in the fibrovascular tissues of PDR, probably through interaction with MT1-MMP and TIMP-2, and suggest the possibility that the activity of MMP-2 and MT1-MMP is involved in the formation of the fibrovascular tissues.
Similar articles
- Enhanced production and activation of progelatinase A mediated by membrane-type 1 matrix metalloproteinase in human papillary thyroid carcinomas.
Nakamura H, Ueno H, Yamashita K, Shimada T, Yamamoto E, Noguchi M, Fujimoto N, Sato H, Seiki M, Okada Y. Nakamura H, et al. Cancer Res. 1999 Jan 15;59(2):467-73. Cancer Res. 1999. PMID: 9927064 - Effect of retinal laser photocoagulation on the activity of metalloproteinases and the alpha(2)-macroglobulin proteolytic state in the vitreous of eyes with proliferative diabetic retinopathy.
Sánchez MC, Luna JD, Barcelona PF, Gramajo AL, Juarez PC, Riera CM, Chiabrando GA. Sánchez MC, et al. Exp Eye Res. 2007 Nov;85(5):644-50. doi: 10.1016/j.exer.2007.07.018. Epub 2007 Aug 6. Exp Eye Res. 2007. PMID: 17826767 - Lysyl oxidase activity in the ocular tissues and the role of LOX in proliferative diabetic retinopathy and rhegmatogenous retinal detachment.
Coral K, Angayarkanni N, Madhavan J, Bharathselvi M, Ramakrishnan S, Nandi K, Rishi P, Kasinathan N, Krishnakumar S. Coral K, et al. Invest Ophthalmol Vis Sci. 2008 Nov;49(11):4746-52. doi: 10.1167/iovs.07-1550. Epub 2008 Jun 19. Invest Ophthalmol Vis Sci. 2008. PMID: 18566459 - MT1-MMP and MMP-7 in invasion and metastasis of human cancers.
Shiomi T, Okada Y. Shiomi T, et al. Cancer Metastasis Rev. 2003 Jun-Sep;22(2-3):145-52. doi: 10.1023/a:1023039230052. Cancer Metastasis Rev. 2003. PMID: 12784993 Review. - Matrix metalloproteinases in diabetic retinopathy: potential role of MMP-9.
Kowluru RA, Zhong Q, Santos JM. Kowluru RA, et al. Expert Opin Investig Drugs. 2012 Jun;21(6):797-805. doi: 10.1517/13543784.2012.681043. Epub 2012 Apr 23. Expert Opin Investig Drugs. 2012. PMID: 22519597 Free PMC article. Review.
Cited by
- Release of Pro-Inflammatory/Angiogenic Factors by Retinal Microvascular Cells Is Mediated by Extracellular Vesicles Derived from M1-Activated Microglia.
Beltramo E, Mazzeo A, Porta M. Beltramo E, et al. Int J Mol Sci. 2023 Dec 19;25(1):15. doi: 10.3390/ijms25010015. Int J Mol Sci. 2023. PMID: 38203187 Free PMC article. - Comparison between metalloproteinases-2 and -9 in healthy subjects, diabetics, and subjects with acute coronary syndrome.
Derosa G, D'Angelo A, Scalise F, Avanzini MA, Tinelli C, Peros E, Fogari E, Cicero AF. Derosa G, et al. Heart Vessels. 2007 Nov;22(6):361-70. doi: 10.1007/s00380-007-0989-6. Epub 2007 Nov 26. Heart Vessels. 2007. PMID: 18043992 - Endothelial glycocalyx in retina, hyperglycemia, and diabetic retinopathy.
Kaur G, Harris NR. Kaur G, et al. Am J Physiol Cell Physiol. 2023 May 1;324(5):C1061-C1077. doi: 10.1152/ajpcell.00188.2022. Epub 2023 Mar 20. Am J Physiol Cell Physiol. 2023. PMID: 36939202 Free PMC article. Review. - The Role of Microglia in Diabetic Retinopathy: Inflammation, Microvasculature Defects and Neurodegeneration.
Altmann C, Schmidt MHH. Altmann C, et al. Int J Mol Sci. 2018 Jan 1;19(1):110. doi: 10.3390/ijms19010110. Int J Mol Sci. 2018. PMID: 29301251 Free PMC article. Review. - Mechanical force enhances MMP-2 activation via p38 signaling pathway in human retinal pigment epithelial cells.
Hou X, Han QH, Hu D, Tian L, Guo CM, Du HJ, Zhang P, Wang YS, Hui YN. Hou X, et al. Graefes Arch Clin Exp Ophthalmol. 2009 Nov;247(11):1477-86. doi: 10.1007/s00417-009-1135-1. Epub 2009 Jul 10. Graefes Arch Clin Exp Ophthalmol. 2009. PMID: 19590887
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Molecular Biology Databases
Research Materials
Miscellaneous