Role Of Matrix Metalloproteinases Research Articles

The role of matrix metalloproteinases in the pathogenetic mechanisms of ischemic stroke

The role of matrix metalloproteinases in the pathogenetic mechanisms of ischemic stroke

Slow-velocity eccentric-only resistance training improves symptoms of type 2 diabetic mellitus patients by regulating plasma MMP-2 and -9.

This study investigated the intervention effect of slow-velocity eccentric-only resistance training on type 2 diabetic mellitus (T2DM) patients based on the role of matrix metalloproteinase-2 and -9 (MMP-2 and -9) in regulating extracellular matrix homeostasis. 50 T2DM patients were randomly divided into the slow-velocity eccentric-only resistance training group (E) and control group (C). The E group performed eccentric-only resistance training 3 times a week, every other day for 10 weeks, while the C group did not. Blood samples were collected before and after training, and subjects were tested for changes in clinical parameters, insulin resistance indices [fasting insulin, homeostatic model assessment insulin resistance (HOMA-IR)], MMP-2 and -9, and hydroxyproline, and muscle strength (12-RM), respectively. After 10 weeks of training, the E group showed significant decreases in fasting glucose (P < .05), insulin (P < .05), insulin resistance indices (P < .05), hemoglobin A1c (HbA1c) (P < .01), triglycerides (P = .06) and MMP-2 (P < .05), while total cholesterol (P < .05), MMP-9 (P < .05), hydroxyproline (P < .01), Creatine Kinase (CK) (P < .05), and muscle strength (P < .001) significantly increased. There were no significant changes in the count of neutrophil, lymphocyte and platelet, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c). Compared with the C group, the E group showed a trend of a significant decrease in triglyceride (P < .05), lymphocyte count (P < .05), fasting glucose (P = .07), and plasma MMP-2 (P < .05), while MMP-9 (P < .05), hydroxyproline (P < .001), and muscle strength (P < .01) significantly increased. However, no significant changes were observed in insulin and insulin resistance indices, HbA1c, total cholesterol, HDL-c, LDL-c, CK, and other inflammatory indicators. Slow-velocity eccentric-only resistance training was beneficial for T2DM, but the potential role of MMP-2 and -9 in regulating extracellular matrix homeostasis is very different in T2DM patients.

The Role of Matrix Metalloproteinase-2 (MMP2) in Colorectal Cancer Progression: Correlation With Clinicopathological Features and Impact on Cellular Processes.

Background Colorectal cancer (CRC) is a prevalent and deadly disease characterized by significant molecular complexity. Matrix metalloproteinase-2 (MMP2) has been implicated in cancer progression due to its role in extracellular matrix degradation, yet comprehensive studies linking MMP2 expression to CRC progression and its molecular mechanisms remain needed. Methodology This study involved 90 CRC patients, with tumor and adjacent normal tissues analyzed via immunohistochemistry (IHC) to assess MMP2 expression. The human CRC cell line SW480 was treated with an MMP2 inhibitor, ARP100, and evaluated for changes in cell migration, invasion, proliferation, and apoptosis using various assays, including MTT, wound-healing, transwell, caspase activity, and western blot analysis. Results High MMP2 expression was significantly associated with advanced tumor stages, lymph node involvement, and metastasis in CRC patients. Compared to normal tissues, MMP2 expression was markedly higher in cancerous tissues. Inhibition of MMP2 in SW480 cells resulted in reduced migration, invasion, and proliferation, and induced apoptosis, evidenced by increased caspase 3 and 9 activities and higher levels of cleaved caspase proteins. Conclusion Elevated MMP2 expression is correlated with advanced CRC and aggressive tumor characteristics. MMP2 inhibition can suppress CRC cell invasiveness, migration, and proliferation while promoting apoptosis, suggesting its potential as a therapeutic target in CRC treatment.

Role of matrix-metalloproteinases and COL4A in type 2 diabetes mellitus and diabetic nephropathy progression

Role of matrix-metalloproteinases and COL4A in type 2 diabetes mellitus and diabetic nephropathy progression

The role of Matrix Metalloproteinase-2 and Galectin-3 as predictive biomarkers for all-cause mortality in patients undergoing transfemoral transcatheter aortic valve implantation

Background Currently available risk scores fail to accurately predict morbidity and mortality in patients with severe symptomatic aortic stenosis who undergo transcatheter aortic valve implantation (TAVI). In this context, biomarkers like matrix metalloproteinase-2 (MMP-2) and Galectin-3 (Gal-3) may provide additional prognostic information. Methods Patients with severe aortic stenosis undergoing consecutive, elective, transfemoral TAVI were included. Baseline demographic data, functional status, echocardiographic findings, clinical outcomes and biomarker levels were collected and analysed. Results The study cohort consisted of 89 patients (age 80.4 ± 5.1 years, EuroScore II 7.1 ± 5.8%). During a median follow-up period of 526 d, 28 patients (31.4%) died. Among those who died, median baseline MMP-2 (alive: 221.6 [170.4; 263] pg/mL vs. deceased: 272.1 [225; 308.8] pg/mL, p < 0.001) and Gal-3 levels (alive: 19.1 [13.5; 24.6] pg/mL vs. deceased: 25 [17.6; 29.5] pg/mL, p = 0.006) were higher than in survivors. In ROC analysis, MMP-2 reached an acceptable level of discrimination to predict mortality (AUC 0.733, 95% CI [0.62; 0.83], p < 0.001), but the predictive value of Gal-3 was poor (AUC 0.677, 95% CI [0.56; 0.79], p = 0.002). Kaplan–Meier and Cox regression analyses showed that patients with MMP-2 and Gal-3 concentrations above the median at baseline had significantly impaired long-term survival (p = 0.004 and p = 0.02, respectively). Conclusions In patients with severe aortic stenosis undergoing transfemoral TAVI, MMP-2 and to a lesser extent Gal-3, seem to have additive value in optimizing risk prediction and streamlining decision-making.

Roles of Matrix Metalloproteinases 2 and 9 in Uterine Leiomyosarcoma.

Uterine leiomyosarcoma (uLMS) is a rare, highly malignant, and invasive cancer, with early metastasis. Mismatch repair (MMR) proteins and matrix metalloproteinases (MMPs) are associated with the occurrence, proliferation, and invasion of most malignant cancers; however, their abnormal expression in uLMS remains poorly clarified. Immunohistochemistry was performed to assess MMR protein and MMP2/9 expression as well as Ki67 marker proliferation in benign and malignant uterine smooth muscle tumors. Data from 28 cases of uterine leiomyoma and 31 cases of uLMS were analyzed. Tumor tissues from patients with uLMS had higher expression levels of MMP2 (p<0.001), MMP9 (p<0.05), and Ki67 (p<0.001) than those from patients with uterine leiomyoma; MMR protein expression showed the opposite trend (p<0.05). uLMS proliferation and metastasis correlated positively with MMP2 (p=0.012 and 0.015, respectively) but negatively with MMP9 (p=0.021 and 0.04, respectively). MMR protein expression did not correlate with uLMS proliferation or metastasis (p>0.05). Expression levels of MMP2 and MMP9 were upregulated in malignant uLMS tumors when compared with those in benign uterine leiomyoma tumors. Increased MMP2 expression might promote uLMS invasion and migration. MMP9 overexpression might be related to uLMS occurrence; however, it protects against uLMS invasion and metastasis. MMP2 and MMP9 may be potential predictors of uLMS cell proliferation, metastasis, and prognosis. These findings could be helpful in developing new strategies for diagnosing and treating uLMS.

The role of matrix metalloproteinase-9 and the tissue inhibitor of metalloproteinase — 1 in endogenous uveitis in children

Purpose: to determine the content of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases — 1 (TIMP-1) in the tear and blood serum (BS) and to analyze how these parameters correlate with the clinical course of endogenous uveitis in children.Materials and methods. 131 eyes with uveitis of 74 patients aged 3 to 17 (mean age 10.57 ± 3.29 years) were examined. The content of MMP-9 was found in 281 samples of the tear and 48 samples of BS. The dynamics of MMP-9 in the tear was studied in 55 patients (100 eyes), in BS — in 9 children. The content of TIMP-1 was studied in 173 tear samples and 25 BS samples. The dynamics of TIMP-1 was studied in the tear of 31 patients (56 eyes). The concentration of MMP-9 and TIMP-1 was determined by enzyme immunoassay (ELISA) using the kits ELISA for MMP-9/ELISA for tissue metalloproteinase inhibitor 1 (Cloud clone corporation, USA).Results. The content of MMP-9 in the tear dropped compared to the control group (p = 0.09). The highest content of MMP-9 in panuveitis was found in the tear as compared to the anterior and intermediate uveitis (p = 0.01). The highest MMP-9 concentration was found in cases of 3rd degree of proliferation, in contrast to the 1st and 2nd degrees (p = 0.16). An increased content of TIMP-1 was found in the tear in subactive/intermediate uveitis in contrast to inactive uveitis (p=0.08). An imbalance of MMP-9 was revealed in relation to TIMP-1 in the tears. In the early postoperative period, an increase in the content of MMP-9 and a decrease in TIMP-1 in the tear returning to the initial level was noted, which corresponds to normal wound healing.Conclusion. An increase in the content of TIMP-1 in the tear is associated with subactive/intermediate uveitis. The content of MMP-9 in the tear correlates with the proliferative process stage. A higher MMP-9 content in the tear in panuveitis, in contrast to the anterior and intermediate uveitis is associated with the involvement of all sections of the choroid of the eye into the inflammatory process. The decrease in the content of MMP-9 in the tears is probably explained by the inhibitory effect of glucocorticosteroid (GCS) therapy.

The Role of Matrix Metalloproteinases in Thoracic Aortic Disease: Are They Indicators for the Pathogenesis of Dissections?

The pathogenesis of aortic aneurysm and dissection continues to be under discussion. Extracellular matrix (ECM) remodeling processes in the aortic wall are hypothesized to be involved in the development of the disorders. Therefore, in a histological study, we investigated the expression of metalloproteases 1 and 9 (MMP1 and MMP9) and their inhibitors (TIMP 1 and TIMP 2) in cardiac surgery patients. In parallel, we studied the aortic roots by echocardiography. Clinical reports of 111 patients (30 women and 81 men) who suffered from aortic aneurysms and aortic dissection were evaluated and studied by transesophageal echocardiography. Seven patients who had coronary heart disease served as "healthy controls". All patients underwent the necessary surgical procedure according to the diagnosed aortic disease in the period from 2007 to 2015. A tissue sample of the aortic biopsies was collected from each patient during surgery. Immunohistochemical staining was performed for MMP1 and MMP9 and TIMP1 and TIMP2 as well. Vascularization was monitored by a CD 31 antibody. In direct comparison, the expressions are not homogeneous. We found the smallest changes in the intima area at all. TIMP 1 and TIMP 2 distribution increases from the lumen of the vessel outward in the wall layers of the aorta. In the case of arteriosclerotic changes, intima had a capillarization, but not in the media. An opposite pattern was found in the dissected aortas. There are differences in the vascularization between the aneurysm and dissection and the different layers, respectively. A different remodeling process of the ECM in comparison to the vascular layers must be hypothesized. Reading the patterns of staining and with regard to the known inhibitory effect of MMP9 on ECM remodeling, but especially TIMP 2 on neoangiogenesis, disturbed nutrition, and dysfunctional vasa vasorum remodeling must be assumed as causes of dissection.

The role of matrix metalloproteinase-2 and miR-196a2 in bronchial asthma pathogenesis and diagnosis

BackgroundBronchial asthma is a persistent inflammatory respiratory condition that restricts the passage of air and causes hyperresponsiveness. Chronic asthma can be classified into three categories: mild, moderate, and severe. Remodeling took place as the extracellular matrix accumulated in the walls of the airways. Inflammation occurs as a result of the damage caused by matrix metalloproteinase-2 (MMP-2) to basement membrane type IV collagen. The severity of asthma may be associated with miR-196a2. The objective of our study was to investigate the underlying mechanisms and clinical relevance of miR-196a2 and MMP-2 serum levels in relation to the severity of asthma. MethodsThis study recruited 85 controls and 95 asthmatics classified as mild, moderate, or severe. Expression of miR-196a2 was measured by quantitative reverse transcriptase PCR. Using the enzyme-linked immunosorbent assay (ELISA), MMP-2, IL-6, and total immunoglobulin E (IgE) levels in the serum of asthmatics of various grades were compared to a control group. MMP-2's diagnostic and prognostic potential was determined using ROC curve analysis. This study also measured blood Eosinophils and PFTs. We examined MMP-2's connections with IgE, blood Eosinophils, and PFTs. ResultsThe current investigation found that miR-196a2 expression was significantly higher in the control group than in asthmatic patients as a whole. The study found that severe asthmatics had higher MMP-2, IL-6, and IgE serum levels than healthy controls. We identified the MMP-2 serum concentration cutoff with great sensitivity and specificity. Significant relationships between MMP-2 serum level and miR-196a2 expression in the patient group with severe asthmatics were found. The MMP-2, IL-6, and IgE serum levels were considerably higher in mild, moderate, and severe asthmatics than controls. The miR-196a2 expression and MMP-2 serum concentration correlated positively with IgE and blood eosinophils % and negatively with all lung function tests in the asthmatic patient group.Conclusion: the study revealed that the elevated miR-196a2 expression and serum concentration of MMP-2, IL-6, and IgE associated with elevated blood eosinophils % is associated with pathophysiology and degree of asthma severity. The miR-196a2 expression and MMP-2 serum concentration have a promising diagnostic and prognostic ability in bronchial asthma.

The role of matrix metalloproteinase-2 in the metastatic cascade: a review

Abstract Matrix metalloproteinase-2 (MMP-2) is a gelatinase and is involved in multiple steps of the metastatic cascade. More than a decade ago an increased expression of MMP-2 in tumour cells or higher serum levels was reported to be a prognostic biomarker for a lower disease-free and overall survival rate. In recent years new evidence has indicated that MMP-2 has an important role in the tumour ecosystem. It is one of the many players in the onco-sphere, involved in interacting between tumour cells, host cells and the microenvironment. It plays a role in the dissemination of tumour cells, the epithelial–mesenchymal and mesenchymal–epithelial transitions, the formation of the pre-metastatic and metastatic niches, dormancy of tumour cells and modulating the immune system. The aim of this review is to highlight these multiple roles in the metastatic cascade and how many signalling pathways can up or down-regulate MMP-2 activity in the different stages of cancer progression and the effect of MMP-2 on the onco-sphere. Research in head and neck cancer is used as an example of these processes. The use of non-specific MMP inhibitors has been unsuccessful showing only limited benefits and associated with high toxicity as such that none have progressed past Phase III trials. Preclinical trials are undergoing using antibodies directed against specific matrix metalloproteinases, these targeted therapies may be potentially less toxic to the patients.

Contribution of Matrix Metalloproteinase-2 Genotypes to Taiwan Pterygium Risk.

In the literature, the studies about the role of matrix metalloproteinase-2 (MMP-2) in pterygium diagnosis are mainly based on its protein expression. The role of MMP-2 variants has never been examined. The aim of this study was to examine the association of MMP-2 genotypes with pterygium risk. MMP-2 rs243865 and rs2285053 were genotyped in 140 pterygium cases and 280 non-pterygium controls by typical polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) genotyping technology. The genotypic frequency of MMP-2 rs243865 CC, CT and TT were 86.4%, 12.9% and 0.7% in the pterygium group and 81.1%, 17.1% and 1.8% in the non-pterygium group (p for trend=0.3389). The variant CT and TT carriers had a 0.70- and 0.38-fold pterygium risk (95%CI=0.39-1.26 and 0.04-3.25, p=0.2982 and 0.6686, respectively). As for MMP-2 rs2285053, the genotypic frequency of CC, CT and TT were 67.1%, 28.6% and 4.3% in the pterygium group, non-significantly different from those in non-pterygium group (p for trend=0.7081). The CT and TT carriers had a 0.88- and 0.71-fold pterygium risk (95%CI=0.56-1.38 and 0.27-1.88, p=0.6612 and 0.6456, respectively). The allelic analysis results showed that MMP-2 rs243865 variant T allele was not associated with pterygium risk (7.1% versus 10.4%, OR=0.67, 95%CI=0.39-1.13, p=0.1649). As for MMP-2 rs2285053, the T allele was not associated with pterygium risk either (18.6% versus 21.1%, OR=0.85, 95%CI=0.59-1.23, p=0.4136). The genotypes at MMP-2 rs243865 or rs2285053 played minor role in determining individual susceptibility for pterygium among Taiwanese.

The role of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) Expression in pelvic organ prolapse: A literature review

Link of Video Abstract: https://youtu.be/Zv9b2Zj96yk Menopause is a physiological process as women get older. Urogenital syndrome, sexual difficulties, and pelvic organ prolapse (POP) are all common complaints among postmenopausal women, and these conditions can negatively impact their quality of life. There are still many unknowns regarding the pathophysiology and mechanisms of POP. Pelvic organ prolapse has been linked to the equilibrium of the extracellular matrix (ECM), which is controlled by matrix metalloproteinases and tissue inhibitors of metalloproteinases. Menopausal women experience a variety of symptoms due to hormonal changes, from urinary tract disturbance, vaginal atrophy, vaginal shortening, up to genital prolapse. Due to the collagen's diminished contractility, POP happens. Matrix metalloproteinase is responsible for breaking down collagen, but TIMP prevents MMP from doing its job. In women with POP caused by the breakdown of the collagen network, MMP-9 exhibits the greatest rise. In order to preserve the health of fibroblasts and collagen in postmenopausal women, increased expression of MMP-9 and decreased expression of TIMP-1 are necessary, which results in a decreased incidence of POP. The expression of MMP-9 in prolapse patients was significantly higher than control patients. In addition, TIMP-1 expression levels were significantly decreased in prolapse patients. Damage to the ECM's equilibrium is caused by increased MMP-9 expression and decreased expression of timp-1, which leads to clinical signs of pelvic organ prolapse.

The possibilities of using the inhibitors of matrix metalloproteinases for keratoplasty

Introduction. The review is devoted to the actual problem of treating patients with keratolysis. The role of matrix metalloproteinases in the pathogenesis of cornea and corneal graft melting is discussed as well as the practical experience of using synthetic metalloproteinase inhibitors in various branches of medicine and in ophthalmology, in particular. In the field of eye diseases, the search for effective methods for the treatment of corneal injuries of various origins, as well as its post-transplant complications, has been underway for a long time. Recent studies have shown that local imbalance of matrix metalloproteinases and their inhibitors system, as well as the immune system status, may play the main role in the outcome of urgent keratoplasty, and the use of synthetic metalloproteinase inhibitors can significantly improve the biological result of the donor cornea transplant. The role of platelets in the regulation of the proteolytic system has not been fully studied. However, some literature data on the platelet-associated inhibitor of metalloproteinases and the use of platelet-rich plasma to correct the collagenolytic activity of enzymes are of great interest to ophthalmologists, due to therapeutic efficacy and simple method of producing its production the autologous platelet-rich plasma.The present brief literature review covers the pathogenesis and clinical features of keratolysis, factors which can affect the outcome of urgent keratoplasty, describes the features of matrix metalloproteinases, their inhibitors, and the plateletrich plasma as a potential endogenous source of a tissue inhibitor of matrix metalloproteinases.Aim. To evaluate the possibility of using inhibitors of matrix metalloproteinases for keratoplasty based on a literature review.Material and methods. To write the review article, we have made the search in the homeland eLibrary.RU database and in the PubMed resource database to select the articles on the topic published in the period from 1985 to 2022.

The Role of Matrix Metalloproteinases in Hemorrhagic Transformation in the Treatment of Stroke with Tissue Plasminogen Activator.

Ischemic stroke is a leading cause of disability and mortality worldwide. The only approved treatment for ischemic stroke is thrombolytic therapy with tissue plasminogen activator (tPA), though this approach often leads to a severe complication: hemorrhagic transformation (HT). The pathophysiology of HT in response to tPA is complex and not fully understood. However, numerous scientific findings suggest that the enzymatic activity and expression of matrix metalloproteinases (MMPs) in brain tissue play a crucial role. In this review article, we summarize the current knowledge of the functioning of various MMPs at different stages of ischemic stroke development and their association with HT. We also discuss the mechanisms that underlie the effect of tPA on MMPs as the main cause of the adverse effects of thrombolytic therapy. Finally, we describe recent research that aimed to develop new strategies to modulate MMP activity to improve the efficacy of thrombolytic therapy. The ultimate goal is to provide more targeted and personalized treatment options for patients with ischemic stroke to minimize complications and improve clinical outcomes.

Sleep deprivation disturbs uterine contractility and structure in pregnant rats: role of matrix metalloproteinase 9 and transforming growth factor-β.

Sleep deprivation (SD) during pregnancy can impact the delivery procedure, with prolongation of the labor duration. Matrix metalloproteinase-9 (MMP9) and transforming growth factor-β (TGF-β) are regulators of uterine remodeling. Their dysregulation is vital for abnormal placentation and uterine enlargement in complicated pregnancies. Therefore, this study aims to explore the outcome of SD throughout pregnancy on ex vivo uterine contractility, MMP9 and TGF-β, and uterine microscopic structure. A total of 24 pregnant rats were divided into two groups. From the first day of pregnancy, animals were exposed to partial SD/6h/day. Uterine in vitro contractile responses to oxytocin, acetylcholine, and nifedipine were assessed. Additionally, uterine levels of superoxide dismutase and malondialdehyde and uterine mRNA expression of MMP9, TGF-β, and apoptotic biomarkers were analyzed. The results showed that SD significantly reduced uterine contractile responses to oxytocin and acetylcholine, while it augmented the relaxing effect of nifedipine. In addition, it significantly increased oxidative stress status, MMP9, TGF-β, and apoptotic biomarkers' mRNA expression. All were accompanied by degeneration of endometrial glands, vacuolization with apoptotic nuclei, and increased area% of collagen fibers. Finally, increased uterine MMP9 and TGF-β mRNA expression during SD clarified their potential role in modulating uterine contractility and structure.

Roles of Matrix Metalloproteinases and Their Natural Inhibitors in Metabolism: Insights into Health and Disease

Matrix metalloproteinases (MMPs) are a family of zinc-activated peptidases that can be classified into six major classes, including gelatinases, collagenases, stromelysins, matrilysins, membrane type metalloproteinases, and other unclassified MMPs. The activity of MMPs is regulated by natural inhibitors called tissue inhibitors of metalloproteinases (TIMPs). MMPs are involved in a wide range of biological processes, both in normal physiological conditions and pathological states. While some of these functions occur during development, others occur in postnatal life. Although the roles of several MMPs have been extensively studied in cancer and inflammation, their function in metabolism and metabolic diseases have only recently begun to be uncovered, particularly over the last two decades. This review aims to summarize the current knowledge regarding the metabolic roles of metalloproteinases in physiology, with a strong emphasis on adipose tissue homeostasis, and to highlight the consequences of impaired or exacerbated MMP actions in the development of metabolic disorders such as obesity, fatty liver disease, and type 2 diabetes.

A functional MMP-9-1562C>T polymorphism, MMP-9 serum levels and nephrolithiasis risk in a southern Chinese population.

The role of matrix metalloproteinase 9 (MMP-9) in the pathophysiology of chronic kidney disease (CKD), which is associated with a nearly two-fold greater risk for urinary calculi compared to people without CKD, has been demonstrated. The aim of the research is to evaluate the association between MMP-9-1562C>T polymorphism, MMP-9 serum levels and nephrolithiasis risk. A hospital-based case-control study involving 302 kidney stone patients and 408 controls without kidney stone from southern China was conducted. Sanger sequencing was used to genotype the MMP-9-1562C>T polymorphism. The serum MMP-9 was measured in 105 kidney stone patients and 77 controls by enzyme-linked immunosorbent assay. Compared to the control group, the CT genotype was more frequent in nephrolithiasis patients (adjusted OR = 1.60, 95% CI = 1.09-2.37: the risk of developing nephrolithiasis in individuals with CT genotype compared to CC genotype). Moreover, there was also a higher frequency of CT/TT genotypes among patients with nephrolithiasis (adjusted OR = 1.49, 95% CI = 1.02-2.19: the risk of developing nephrolithiasis in individuals with CT/TT genotypes compared to CC genotype). The risk remained for the subgroups of patients aged >53, smokers with pack-years of smoking >20, non-drinkers, non-diabetic patients, patients with hypertension, recurrent episodes and calcium oxalate stones (OR = 2.26, 95% CI = 1.31-3.91; OR = 5.47, 95% CI = 1.10-27.30; OR = 1.76, 95% CI = 1.14-2.72; OR = 1.54, 95% CI = 1.03-2.30; OR = 1.97, 95% CI = 1.01-3.82; OR = 1.67, 95% CI = 1.06-2.62; OR = 1.54, 95% CI = 1.02-2.32, respectively). Biochemical parameters did not differ between genotypes. Compared to controls (18.57 ± 5.80 ng/mL), nephrolithiasis patients had significantly higher serum MMP-9 levels (30.17 ± 6.78 ng/mL, p < 0.001). The serum MMP-9 levels of patients with CT/TT genotypes of MMP-9-1562C>T were significantly higher than those with CC genotype (32.00 ± 6.33 vs. 29.13 ± 6.85 ng/mL, p = 0.037). The MMP-9-1562C>T polymorphism in association with its soluble protein increased the risk of kidney stone, thus suggesting it could be used as a susceptibility biomarker for nephrolithiasis. Further functional studies and larger studies that include environmental exposure data are needed to confirm the findings.

Role of Matrix Metalloproteinase–9 in the Pathogenesis of Preeclampsia

Objectives: The goal of this research was to investigate whether metalloproteinases could be used as predictors of preeclampsia (PE) during pregnancy. Materials and Methods: This case-control study included 100 pregnant women which they further grouped into PE and control group (each composed of 50 women). Both groups were further subdivided according to their gestational age (GA), using the 37th week of gestation as a divider, as preterm and term infants. Results: In both preterm (P=0.001) and term infants (P=0.001), mean metalloproteinase-9 (MMP-9) was considerably lower in PE mothers compared to controls, with the difference being greater in preterm infants. In ROC analysis, MMP-9 showed excellent ability to predict PE in preterm infants (AUC = 0.980, cut-off ≤26.2) and good ability to predict PE in term infants (AUC 0.770, cut-off ≤ 34.4). Conclusions: The matrix MMP-9 is a non-specific predictor of PE for term and preterm pregnant women, with higher accuracy for preterm pregnant women.

Amelioration of Pulmonary Fibrosis by Matrix Metalloproteinase-2 Overexpression

Idiopathic pulmonary fibrosis is a progressive and fatal disease with a poor prognosis. Matrix metalloproteinase-2 is involved in the pathogenesis of organ fibrosis. The role of matrix metalloproteinase-2 in lung fibrosis is unclear. This study evaluated whether overexpression of matrix metalloproteinase-2 affects the development of pulmonary fibrosis. Lung fibrosis was induced by bleomycin in wild-type mice and transgenic mice overexpressing human matrix metalloproteinase-2. Mice expressing human matrix metalloproteinase-2 showed significantly decreased infiltration of inflammatory cells and inflammatory and fibrotic cytokines in the lungs compared to wild-type mice after induction of lung injury and fibrosis with bleomycin. The computed tomography score, Ashcroft score of fibrosis, and lung collagen deposition were significantly reduced in human matrix metalloproteinase transgenic mice compared to wild-type mice. The expression of anti-apoptotic genes was significantly increased, while caspase-3 activity was significantly reduced in the lungs of matrix metalloproteinase-2 transgenic mice compared to wild-type mice. Active matrix metalloproteinase-2 significantly decreased bleomycin-induced apoptosis in alveolar epithelial cells. Matrix metalloproteinase-2 appears to protect against pulmonary fibrosis by inhibiting apoptosis of lung epithelial cells.

Comparison of MMP-2 and TIMP-2 expressions in yak testes at different ages.

This study aimed to investigate the distribution and expression of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) in yak testes. The testes of healthy yaks at different ages: newborn [3 days], young [1 year], adult [4 years], and old [9 years] were collected for microscopic analyses using hematoxylin and eosin staining, immunohistochemistry and immunofluorescence, as well as western blot to compare the expression of MMP-2 and TIMP-2. Furthermore, the levels of MMP-2mRNA and TIMP-2mRNA was detected by real-time quantitative polymerase chain reaction (qPCR). The results of immunohistochemistry and immunofluorescence demonstrated that MMP-2 and TIMP-2 were mainly located in gonocytes of newborn, Sertoli cells of young, spermatozoa of adult and Leydig cells of old. The protein levels of MMP-2 and TIMP-2 exhibited a downward from newborn to adult, but increased again in old yaks. The analysis of qPCR showed that MMP-2 was higher in young compared with newborn or adult(**P<0.01), but a lower expression was detected in adult compared with old yak testicular tissues (*P<0.05). Compared with adults, TIMP-2 was significantly higher in newborn and young yaks (**P<0.01), and slightly higher in old yaks (*P<0.05). Hence, The location of MMP-2 and TIMP-2 in gonocytes were associated with the development of newborn yak testes. The expression of MMP-2 and TIMP-2 in Sertoli cells at young and adult yaks suggested that they provided a clue for the regulation of spermatogenesis. The positive labeling of MMP-2 and TIMP-2 in Leydig cells in old yaks suggested that both may be involved in the interstitial metabolism of the testes during this period. This study revealed the possible role of MMP-2 and TIMP-2 in testicular functionality of yaks at different ages.