Уважаемые пользователи!

Данный сайт содержит информацию для людей с медицинским образованием и специалистов здравоохранения.
Входя на сайт, Вы подтверждаете свое согласие с Условиями использования и Политикой конфиденциальности.



Dear visitor!
This site contains medical information for healthcare professionals.
You can go further, if you agree with Terms and Conditions and Privacy Policy on this site.

Matrix metalloproteinases-1, -13 and their tissue inhibitor-1 in endocrine ophthalmopathy

Cover Page
Open Access Open Access
Restricted Access Subscription Access

Abstract


Effective regeneration of damaged soft orbital tissues in Graves’ ophthalmopathy (GO) requires coordinated remodeling of the extracellular matrix. Matrix metalloproteinases (MMPs) play an important role in the synthesis and degradation homeostasis of extracellular matrix components in various physiological and pathological conditions. Their proteolytic activity is inhibited by tissue inhibitors of metalloproteinases (TIMP). The biochemical processes taking place in extraocular muscles and retrobulbar tissue fibrogenesis in GO are not fully understood.

Aims — to assess some biochemical mechanisms of extraocular muscles and retrobulbar tissue fibrogenesis in GO patients.

Material and methods. The study included 65 people (130 eyes) at the age of 43 (35–50) years. Three groups of subjects were formed: 32 patients with a moderate GO severity (clinical group), 18 patients with autoimmune thyroid pathology without GO (comparison group), and 15 healthy persons (control). The diagnosis was based on clinical, laboratory, and instrumental data. A comprehensive ophthalmologic examination and blood sampling for determination of MMP-1, -13, TIMP-1, sulfated glycosaminoglycans (sGAG) and antibodies to thyroid-stimulating hormone receptor (TSHRAbs) were conducted. The data were statistically processed using the program Statistica 10.0.

Results. An elevated level of MMP-13, observed in all GO patients (p<0.05). For the active phase of GOP, the comparison with the control group showed a 3.5-fold increase in MMP-13 (p<0.001) and 1.17-fold rise in TIMP-1 (p>0.05). Pulse glucocorticoid therapy reduced MMP-13 by 48.6% (p<0.001), TIMP-1 by 2.7% (p<0.001), and TSHRAbs — by 93% (p<0.001) compared with active GO, but these indicators were higher than the reference limits of control (p>0.05). In inactive GO, despite increased MMP-13, TIMP-1 decreased to the reference values (p=0.533). There were no significant differences in MMP-1 in groups of subjects (p=0.865).

Conclusions. We have found imbalance between MMP-13 and TIMP-1 production in different activity phases of GO. Active GO is characterized by an increase in serum MMP-13 and TIMP-1. Dysregulation of intercellular matrix remodeling, possibly, underlies the development of extraocular muscles and retrobulbar tissue fibrosis in GO.


Elizaveta S. Taskina

Chita State Medical Academy

Author for correspondence.
Email: taskins@yandex.ru
ORCID iD: 0000-0002-6223-8888
SPIN-code: 5687-2122

Russian Federation, 39a, Gorky street, Chita, 672000

post-graduate student at the Department of Ophthalmology

Svetlana V. Kharintseva

Chita State Medical Academy

Email: s.v.19.28@mail.ru
ORCID iD: 0000-0002-8899-5465
SPIN-code: 6788-2110

Russian Federation, 39a, Gorky street, Chita, 672000

MD, PhD, Professor

  1. Дедов И.И., Мельниченко Г.А., Свириденко Н.Ю., и др. Федеральные клинические рекомендации по диагностике и лечению эндокринной офтальмопатии при аутоиммунной патологии щитовидной железы. // Проблемы Эндокринологии. — 2015. — Т. 61. — № 1. — С. 61-74. [Dedov II, Melnichenko GA, Sviridenko NYu, et al. Federal clinical recommendations on diagnostics and treatment of endocrine ophthalmopathy associated with autoimmune thyroid pathology. Problems of Endocrinology. 2015;61(1):61-74. (In Russ.)]. doi: https://doi.org/10.14341/probl201561161-74
  2. Петунина Н.А., Трухина Л.В., Мартиросян Н.С. Эндокринная офтальмопатия: современный взгляд. // Проблемы Эндокринологии. — 2012. — Т. 58. — № 6. — C. 24-32. [Petunina NA, Trukhina LV, Martirosyan NS. Endocrine ophthalmopathy: state-of-the-art approaches. Problems of Endocrinology. 2012;58(6):24-32. (In Russ.)]. doi: https://doi.org/10.14341/probl201258624-32
  3. Таскина Е.С., Харинцева С.В., Харинцев В.В. Современные представления о патогенезе повреждения глазодвигательных мышц и ретробульбарной клетчатки при эндокринной офтальмопатии. // Забайкальский Медицинский Вестник. — 2017. — № 2. — С. 175-184. [Taskina ES, Kharintseva SV, Kharintsev VV. Current insights into the pathogenesis of the extraocular muscles and retrobulbar tissue impairments in endocrine ophthalmopathy. Zabaykal’skiy Meditsinskiy Vestnik. 2017;(2):175-184. (In Russ.)].
  4. Dik WA, Virakul S, Van Steensel L. Current perspectives on the role of orbital fibroblasts in the pathogenesis of graves’ ophthalmopathy. Exp Eye Res. 2016;142:83-91. doi: https://doi.org/10.1016/j.exer.2015.02.007
  5. Харинцев В.В., Серебрякова О.В., Серкин Д.М., и др. Роль некоторых про- и противовоспалительных цитокинов в течении эндокринной офтальмопатии. // Забайкальский Медицинский Вестник. — 2016. — № 2. — С. 33-40. [Kharintsev VV, Serebryakova OV, Serkin DM, et al. The role of some pro- and anti-inflammatory cytokines in the course of endocrine ophthalmopathy. Zabaykal’skiy Meditsinskiy Vestnik. 2016;2:33-40. (In Russ.)].
  6. Bahn RS. Current insights into the pathogenesis of graves’ ophthalmopathy. Horm Metab Res. 2015;47(10):773-778. doi: https://doi.org/10.1055/s-0035-1555762
  7. Apte SS, Parks WC. Metalloproteinases: a parade of functions in matrix biology and an outlook for the future. Matrix Biol. 2015;44-46:1-6. doi: https://doi.org/10.1016/j.matbio.2015.04.005
  8. Шадрина А.С., Плиева Я.З., Кушлинский Д.Н., и др. Классификация, регуляция активности, генетический полиморфизм матриксных металлопротеиназ в норме и при патологии. // Альманах Клинической Медицины. — 2017. — Т. 45. — № 4. — С. 266-279. [Shadrina AS, Plieva YaZ, Kushlinsky DN, et al. Classification, regulation of activity, genetic polymorphism of matrix metalloproteinases in norm and in pathology. Almanac of Clinical Medicine. 2017;45(4):266-279. (In Russ.)]. doi: https://doi.org/10.18786/2072-0505-2017-45-4-266-279
  9. Bartalena L, Baldeschi L, Boboridis K, et al. The 2016 European thyroid association/European group on graves’ orbitopathy guidelines for the management of graves’ orbitopathy. Eur Thyroid J. 2016;5(1):9-26. doi: https://doi.org/10.1159/000443828
  10. Krieger CC, Gershengorn MC. A modified ELISA accurately feasures secretion of high molecular weight hyaluronan (HA) by graves’ disease orbital cells. Endocrinology. 2014;155(2):627-634. doi: https://doi.org/10.1210/en.2013-1890
  11. Krieger CC, Neumann S, Place Rf, et al. Bidirectional TSH and IGF-1 receptor cross talk mediates stimulation of hyaluronan secretion by graves’ disease immunoglobins. J Clin Endocrinol Metab. 2015;100(3):1071-1077. doi: https://doi.org/10.1210/jc.2014-3566
  12. Суфияров И.Ф., Хасанов А.Г., Нуртдинов М.А., и др. Высокий уровень гликозаминогликанов сыворотки крови как независимый предиктор развития спаечной болезни брюшины. // Креативная Хирургия и Онкология. — 2017. — Т. 7. — № 2. — С. 48-53. [Sufiyarov IF, Khasanov AG, Nurtdinov MA, et al. High level of glycosaminoglycans of blood serumas an independent predictor of the developing peritoneum adhesive disease. Creative Surgery and Oncology. 2017;7(2):48-53. (In Russ.)]. doi: https://doi.org/10.24060/2076-3093-2017-7-2-48-53
  13. Рогова Л.Н., Шестернина Н.В., Замечник Т.В., Фастова И.А. Матриксные металлопротеиназы, их роль в физиологических и патологических процессах (обзор). // Вестник Новых Медицинских Технологий. — 2011. — Т. 18. — № 2 — С. 86-89. [Rogova LN, Shesternina NV, Zamechnik TV, Fastova IA. Matrix metalloproteinases, their role in physiological and pathological processes (review). Bulletin of New Medical Technologies. 2011; 18(2):86-89. (In Russ.)].
  14. Говорин А.В., Рацина Е.В., Соколова Н.А. Изменения показателей матриксных металлопротеиназ и их тканевых ингибиторов при различных формах ишемической болезни сердца. // Сибирский Медицинский Журнал. — 2014. — Т. 124. — № 1. — C. 27-32. [Govorin AV, Ratsina EV, Sokolova NA. Changes in matrix metalloproteinases and their tissue inhibitors in different forms of ischemic heart disease. Siberian Medical Journal. 2014;124(1):27-32. (In Russ.)].
  15. Arpino V, Brock M, Gill SE. The role of timps in regulation of extracellular matrix proteolysis. Matrix Biol. 2015;44-46:247-254. doi: https://doi.org/10.1016/j.matbio.2015.03.005
  16. Brew K, Nagase H. The tissue inhibitors of metalloproteinases (TIMPS): an ancient family with structural and functional diversity. Biochim Biophys Acta. 2010;1803(1):55-71. doi: https://doi.org/10.1016/j.bbamcr.2010.01.003
  17. Myśliwiec J, Adamczyk M, Pawłowski P, et al. Serum gelatinases (MMP-2 and MMP-9) and VCAM-1 as a guideline in a therapeutic approach in Graves' ophthalmopathy. Endokrynol Pol. 2007; 58(2):105-109.
  18. Kim H, Choi YH, Park SJ, et al. Antifibrotic effect of pirfenidone on orbital fibroblasts of patients with thyroid-associated ophthalmopathy by decreasing TIMP-1 and collagen levels. Invest Ophthalmol Vis Sci. 2010;51(6):3061-3066. doi: https://doi.org/10.1167/iovs.09-4257
  19. Lei H, Leong D, Smith LR, Barton ER. Matrix metalloproteinase-13 is a new contributor to skeletal muscle regeneration and critical for myoblast migration. Am J Physiol Cell Physiol. 2013;305(5):C529-C538. doi: https://doi.org/10.1152/ajpcell.00051.2013
  20. Wang W, Pan H, Murray K, et al. Matrix metalloproteinase-1 promotes muscle cell migration and differentiation. Am J Pathol. 2009;174(2):541-549. doi: https://doi.org/10.2353/ajpath.2009.080509

Supplementary files

There are no supplementary files to display.

Views

Abstract - 466

PDF (Russian) - 4

Remote (Russian) - 1

PlumX


Copyright (c) 2019 Taskina E.S., Kharintseva S.V.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.