Role of matrix metalloproteinase-9 in apoptosis of hippocampal neurons in rats during early brain injury after subarachnoid hemorrhage

Оперативное вмешательство - один из основных методов лечения глаукомы. Однако развитие избыточного рубцевания созданных путей оттока определяет результат хирургического лечения в отдаленные сроки. Процессы рубцевания на данный момент недостаточно изучены. Цель исследования - оценка роли матриксной металлопротеиназы-9, ее ингибиторов в процессах рубцевания у больных с первичной открытоугольной глаукомой после оперативного лечения. Методика. Для выявления возможных маркеров избыточного рубцевания методом твердофазного иммуноферментного анализа определяли содержание матриксных металлопротеиназ-9, тканевых ингибиторов металлопротеиназ 2 и -3 в слезной жидкости у 37 пациентов с активной стадией первичной остроугольной глаукомы в динамике послеоперационного периода. Средний возраст пациентов составил 52,8 лет. В зависимости от исхода оперативного вмешательства все пациенты были разделены на 2 группы - с благоприятным исходом (без избыточного рубцевания) и с неблагоприятным исходом (с избыточным рубцеванием) на месте сформированных дополнительных путей оттока внутриглазной жидкости в послеоперационном периоде. Группа контроля включала 20 человек в возрасте от 50 до 66 лет без сопутствующей офтальмологической и соматической патологии в стадии обострения. Результаты. В динамике показано изменение концентрации матриксной металлопротеиназы-9 и ее ингибиторов в послеоперационном периоде. Анализ данных свидетельствует об обратной зависимости уровня матриксной металлопротеиназы-9 и тканевых ингибиторов металлопротеиназы 2 и 3 типов с исходом операции - чем выше концентрация металлопротеиназы-9 и ниже концентрация тканевых ингибиторов металлопротеиназ 2, -3 в слезной жидкости, тем выше вероятность неблагоприятного исхода в виде рубцевания сформированных дополнительных путей оттока внутриглазной жидкости в послеоперационном периоде. Заключение. Мониторинг уровня металлопротеиназ и их тканевых ингибиторов после проведения хирургического лечения пациентов с первичной открытоугольной глаукомой позволяет прогнозировать раннее рубцевание, дает возможность разработки новых методов лечения как в раннем, так и в позднем послеоперационном периоде. Surgery is one of the major treatments for glaucoma; however excessive scarring of created outflow patways affects the long-term outcome. At the present time, scarring processes are not sufficiently studied. Aim. To evaluate the role of matrix metalloproteinase 9 and its inhibitors in scarring after surgical treatment of open-angle glaucoma. Methods. Concentrations of matrix metalloproteinase 9 and tissue inhibitors of metalloproteinases 2 and 3 were measured in tear fluid of 37 patients (mean age, 52.8) with active primary open-angle glaucoma in dynamics during the postoperative period to identify possible markers of excessive scarring. Based on the surgery outcome, all patients were divided into two groups, with a favorable outcome (without excessive scarring) and an unfavorable outcome (with excessive scarring) in the created additional outflow pathways for the intraocular fluid in the postoperative period. The control group included 20 subjects aged 50-66 without eye disease or somatic disease at exacerbation stage. Results. Analysis of changes in concentrations of matrix metalloproteinase 9 and its inhibitors in the postoperative period showed their inverse relationship with the surgery outcome. The higher was the metalloproteinase 9 level and the lower the level of tissue inhibitors of metalloproteinases 2 and 3 the higher was the probability of unfavorable outcome evident as excessive scarring of the formed additional pathways for tear fluid outflow in the postoperative period. Conclusion. Postoperative monitoring of metalloproteinases and their tissue inhibitors allows to predict early scarring and to develop new treatments both in early and late postoperative periods.

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Role of matrix metalloproteinase-2 and matrix metalloproteinase-9 in patients with recurrent miscarriage

Journal of Reproductive Immunology ◽

10.1016/j.jri.2014.09.049 ◽

2014 ◽

Vol 106 ◽

pp. 20

Author(s):

Y. Obayashi ◽

Y. Ozaki ◽

S. Kurakane ◽

S. Goto ◽

K. Kumagai ◽

...

Keyword(s):

Matrix Metalloproteinase ◽

Recurrent Miscarriage ◽

Matrix Metalloproteinase 9 ◽

Matrix Metalloproteinase 2 ◽

Metalloproteinase 9

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The Role of Matricellular Proteins in Experimental Subarachnoid Hemorrhage-Induced Early Brain Injury

Cellular and Molecular Approaches to Regeneration and Repair - Springer Series in Translational Stroke Research ◽

10.1007/978-3-319-66679-2_20 ◽

2017 ◽

pp. 397-407 ◽

Cited By ~ 3

Author(s):

Lei Liu ◽

Hidenori Suzuki

Keyword(s):

Subarachnoid Hemorrhage ◽

Brain Injury ◽

Early Brain Injury ◽

Matricellular Proteins ◽

Experimental Subarachnoid Hemorrhage

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SKIP Downregulation Increases TGF-β1-Induced Matrix Metalloproteinase-9 Production in Transformed Keratinocytes

Scientifica ◽

10.6064/2012/861647 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Jelena Kocić ◽

Victor Villar ◽

Aleksandra Krstić ◽

Juan F. Santibanez

Keyword(s):

Matrix Metalloproteinase ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Regulatory Protein ◽

Mek Inhibitor ◽

Matrix Metalloproteinase 9 ◽

Transformed Cells ◽

Interacting Protein ◽

Metalloproteinase 9

Transforming growth factor-beta (TGF-β1) is a potent inductor of matrix metalloproteinase-9 (MMP-9) in transformed cells. Recently, Ski-interacting protein (SKIP) has been described as a regulator of TGF-β1 signal transduction, but its role in the induction of cell malignance by TGF-β1 has not been fully elucidated so far. In the present study, we analyzed the role of SKIP on TGF-β1-induced MMP-9 production. Mouse transformed keratinocytes (PDV) were stably transfected with SKIP antisense construct. We observed that SKIP depletion provoked an enhancement in the expression of MMP-9 in response to TGF-β1 treatment. The downregulation of SKIP produced an enhancement in TGF-β1-activated ERK1,2 MAP kinase as well as increased transactivation of downstream Elk1 transcription factor. The increased MMP-9 production in response to TGF-β1 was dependent of MAPK activation as PD98059, an MEK inhibitor, reduced MMP-9 expression in SKIP antisense transfected cells. Thus, we propose SKIP as a regulatory protein in TGF-β1-induced MMP-9 expression acting by controlling ERK1,2 signaling in transformed cells.

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Abstract WP288: Inter-Alpha Inhibitor Proteins Reduce the Presence of Neutrophils and Matrix Metalloproteinase-9 Positive Neutrophils in Damaged Brain Regions of Neonates with Hypoxic-Ischemic (HI) Brain Injury

Stroke ◽

10.1161/str.48.suppl_1.wp288 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Adriel Barrios-Anderson ◽

Xiaodi Chen ◽

Yow-Pin Lim ◽

Barbara S Stonestreet

Keyword(s):

Brain Injury ◽

Corpus Callosum ◽

Matrix Metalloproteinase ◽

Right Hemisphere ◽

Brain Regions ◽

Matrix Metalloproteinase 9 ◽

Male Rats ◽

Control Group ◽

Neonatal Rats ◽

Metalloproteinase 9

Introduction: Inter-alpha inhibitor proteins (IAIPs) are immunomodulatory proteins that play a significant anti-inflammatory role in hypoxic ischemic (HI) brain injury. We have shown that administering IAIPs after HI improves histopathological brain injury, brain weight, and behavioral outcomes in neonatal rats. Neutrophils are specialized leukocytes known to infiltrate the brain parenchyma and exacerbate neuronal injury after HI. One molecular mechanism by which neutrophils exert damage on the blood-brain barrier (BBB) and brain tissue after ischemia is by the release of matrix metalloproteinase-9 (MMP9), an enzyme that breaks down the extracellular matrices of surrounding cells. Objective: To determine the effect of IAIPs on neutrophil infiltration and release of MMP9 in neonatal rats after HI. Methods: The Vannucci model was used to induce neonatal HI in postnatal day 7 rats that were assigned to a Non-ischemic sham-control group (Sham, n=12), right-sided carotid ligation with exposure to hypoxia (8% oxygen for 90 min) treated with placebo group (PL-HI, n=17), or an IAIP treated group (IAIP-HI, n=17). Rat sex was recorded. IAIP (30 mg/kg) or PL was given intraperitoneally at 0, 24 and 48 h after HI. We removed the rat brain after 72h and performed immunohistochemistry using MPO (neutrophil selective) and MMP9 fluorescent markers. We performed stereological analyses with the StereoInvestigator 10.0 Fractionator probe without knowledge of group assignment to quantify neutrophils and MMP9 positive cells present within the right hemisphere, cortex, corpus callosum, and hippocampus. Results: MPO positive cells were significantly reduced in male IAIP treated rats compared with PL-HI in the overall damaged hemisphere (p<0.01) and the corpus callosum (p<0.05). Further, we observed MPO and MMP9 co-localization, and IAIP treatment reduced the presence of MMP9 positive neutrophils in the cortex of male rats compared to placebo (P<0.05).

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