Immunohistochemical characteristics of MMP-9 and TIMP-1 markers expression in the cerebral cortex in diabetes mellitus type 2
DOI:
https://doi.org/10.14739/2310-1210.2020.4.208355Keywords:
diabetes mellitus, angiogenesis, MMP-9, TIMP-1, MMP-9/TIMP-1Abstract
Aim – to study the features of immunohistochemical expression of MMP-9, TIMP-1, MMP/TIMP ratio in the cerebral cortex in diabetes mellitus type 2.
Materials and methods. A pathomorphological and immunohistochemical study of the section material of brain tissue conducted in 3 groups of observations: group I – control without diabetes and cerebrovascular pathology, group II – deceased patients with dyscirculatory-ischemic encephalopathy (DIE), group III – deceased patients with diabetes mellitus type 2 (DM).
Results. Increased expression of MMP-9 in DIE group and in deceased patients with DM type 2 (MMP-9 in the control group – 0.434 (0.399; 0.792) %, in DIE group – 0.652 (0.398; 1.103) %, in DM type 2 group – 0.829 (0.636; 1.034) % has been found. A significant decrease in TIMP-1 expression was detected in DM type 2 (TIMP-1 – in the control group 0.449 (0.254; 0.601) %, in group of DIE – 0.444 (0.306; 0.688) %, in DM type 2 group – 0.278 (0.196; 0.554) %. A statistically significant increase in the MMP/TIMP ratio (Р ˂ 0.05) was observed in DM, the median was 2.732 (1.665; 4.643); this indicator was 1.386 (0.618; 2.29) in the control group and 1.528 (0.619; 3.056) (Р ˃ 0.05) in DIE group.
Conclusions. An increase in the level of MMP-9 expression and a decrease in the expression level of TIMP-1 in the cerebral cortex in diabetes mellitus type 2 promote increased blood-brain barrier permeability and is an important link in the pathogenesis of diabetic microangiopathy.
References
Rempe, R. G., Hartz, A. M. S., & Bauer, B. (2016). Matrix metalloproteinases in the brain and blood-brain barrier: Versatile breakers and makers. Journal of Cerebral Blood Flow & Metabolism, 36(9), 1481-1507. https://doi.org/10.1177/0271678X16655551
Reinhard, S. M., Razak, K., & Ethell, I. M. (2015). A delicate balance: role of MMP-9 in brain development and pathophysiology of neurodevelopmental disorders. Frontiers in cellular neuroscience, 9, Article 280. https://doi.org/10.3389/fncel.2015.00280
Wadood, S. A., Shawk, R., & Hashem, R. (2015). Variants of MMP-9 and TIMP-1 levels could be a predictor of an early development of cardiovascular diseases in type 2 Diabetes among Iraqi patients. Iraqi Journal of Science, 56(1C), 622-632.
de Senna, P. N., Xavier, L. L., Bagatini, P. B., Saur, L., Galland, F., Zanotto, C., Bernardi, C., Nardin, P., Gonçalves, C. A., & Achaval, M. (2015). Physical training improves non-spatial memory, locomotor skills and the blood brain barrier in diabetic rats. Brain research, 1618, 75-82. https://doi.org/10.1016/j.brainres.2015.05.026
Setyopranoto, I., Malueka, R. G., Panggabean, A. S., Widyadharma, I., Sadewa, A. H., Lamsudin, R., & Wibowo, S. (2018). Association between Increased Matrix Metalloproteinase-9 (MMP-9) Levels with Hyperglycaemia Incidence in Acute Ischemic Stroke Patients. Open access Macedonian journal of medical sciences, 6(11), 2067-2072. https://doi.org/10.3889/oamjms.2018.459
Zhang, J.-X., Zhang, Z.-Y., & Cheng, Y. (2017). Elevated MMP-1 and TIMP-1 are related with acute cerebral infarction patients with diabetes mellitus. International Journal of Clinical and Experimental Medicine, 10(12), 16555-16561.
Piccardi, B., Palumbo, V., Nesi, M., Nencini, P., Gori, A. M., Giusti, B., Pracucci, G., Tonelli, P., Innocenti, E., Sereni, A., Sticchi, E., Toni, D., Bovi, P., Guidotti, M., Tola, M. R., Consoli, D., Micieli, G., Tassi, R., Orlandi, G., Perini, F., … Inzitari, D. (2015). Unbalanced Metalloproteinase-9 and Tissue Inhibitors of Metalloproteinases Ratios Predict Hemorrhagic Transformation of Lesion in Ischemic Stroke Patients Treated with Thrombolysis: Results from the MAGIC Study. Frontiers in neurology, 6, Article 121. https://doi.org/10.3389/fneur.2015.00121
Moore, C. S., & Crocker, S. J. (2012). An alternate perspective on the roles of TIMPs and MMPs in pathology. The American Journal of Pathology, 180(1), 12-16. https://doi.org/10.1016/j.ajpath.2011.09.008
Turner, R. J., & Sharp, F. R. (2016). Implications of MMP9 for Blood Brain Barrier Disruption and Hemorrhagic Transformation Following Ischemic Stroke. Frontiers in Cellular Neuroscience, 10, Article 56. https://doi.org/10.3389/fncel.2016.00056
Watanabe, R., Maeda, T., Zhang, H., Berry, G. J., Zeisbrich, M., Brockett, R., Greenstein, A. E., Tian, L., Goronzy, J. J., & Weyand, C. M. (2018). MMP (Matrix Metalloprotease)-9-Producing Monocytes Enable T Cells to Invade the Vessel Wall and Cause Vasculitis. Circulation Research, 123(6), 700-715. https://doi.org/10.1161/circresaha.118.313206
Peres, G. B., Jasiulionis, M. G., & Michelacci, Y. M. (2014). Matrix Metalloproteases in Streptozotocin Model of Diabetes Mellitus. In E. L. Gauther (Ed.), Streptozotocin: Uses, Mechanism of Action and Side Effects (pp. 81-98). Nova Science Publishers.
Zhang, Z., Wu, X., Cai, T., Gao, W., Zhou, X., Zhao, J., Yao, J., Shang, H., Dong, J., & Liao, L. (2015). Matrix Metalloproteinase 9 Gene Promoter (rs 3918242) Mutation Reduces the Risk of Diabetic Microvascular Complications. International Journal of Environmental Research and Public Health, 12(7), 8023-8033. https://doi.org/10.3390/ijerph120708023
Lorente, L., Martín, M. M., Ramos, L., Cáceres, J. J., Solé-Violán, J., Argueso, M., Jiménez, A., Borreguero-León, J. M., Orbe, J., Rodríguez, J. A., & Páramo, J. A. (2015). Serum tissue inhibitor of matrix metalloproteinase-1 levels are associated with mortality in patients with malignant middle cerebral artery infarction. BMC Neurology, 15, Article 111.
https://doi.org/10.1186/s12883-015-0364-7
Kowluru, R. A. (2010). Role of Matrix Metalloproteinase-9 in the Development of Diabetic Retinopathy and Its Regulation by H-Ras. Investigative Opthalmology & Visual Science, 51(8), 4320-4326. https://doi.org/10.1167/iovs.09-4851
Omar, G., Sayed, G., Ghanem, A., Mohamed, N., & El-Kholy, M. (2018). Association of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 levels with diabetic foot ulcer in Egyptians with type 2 diabetes mellitus. Journal of Medicine in Scientific Research, 1(4), 266-270. https://doi.org/10.4103/jmisr.jmisr_80_18
Morishita, T., Uzui, H., Mitsuke, Y., Amaya, N., Kaseno, K., Ishida, K., Fukuoka, Y., Ikeda, H., Tama, N., Yamazaki, T., Lee, J.-D., & Tada, H. (2017). Association between matrix metalloproteinase-9 and worsening heart failure events in patients with chronic heart failure. ESC Heart Failure, 4(3), 321-330. https://doi.org/10.1002/ehf2.12137
Nagy, B., Woth, G., Mérei, Á., Nagy, L., Lantos, J., Menyhei, G., Bogár, L., & Mühl, D. (2016). Perioperative time course of matrix metalloproteinase-9 (MMP-9), its tissue inhibitor TIMP-1 & S100B protein in carotid surgery. Indian Journal of Medical Research, 143(2), 220-226. https://doi.org/10.4103/0971-5916.180212
Ikemoto, S., Matsuura, R., Hamano, S.-I., Daida, A., Kubota, J., Hirata, Y., & Koichihara, R. (2018). Elevated Serum MMP-9 and MMP/TIMP-1 Ratio in Patients with Migrainous Infarction and Hemiplegic Migraine. Journal of Neurology and Neuroscience, 9(6), Article 278. https://doi.org/10.21767/2171-6625.1000278
Downloads
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access)
