scholarly journals Gelatinases Increase in Bleomycin-induced Systemic Sclerosis Mouse Model

2019 ◽  
Author(s):  
Fatemeh Vafashoar ◽  
Kazem Mousavizadeh ◽  
Hadi Poormoghim ◽  
Abbas Tavasoli ◽  
Tahereh Musavi Shabestari ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Mouse Model ◽  
Matrix Metalloproteinase ◽  
Gelatin Zymography ◽  
Gelatinolytic Activity ◽  
Matrix Metalloproteinase 2 ◽  
Control Group ◽  
Tissue Sections ◽  
Tissue Homogenates ◽  
And Control

Systemic sclerosis is a fibrotic autoimmune disease in which aberrant remodeling of the extracellular matrix in organs disturbs their functionalities. The aim of this study was to investigate the expression of gelatinases on systemic sclerosis. Consequently, a mouse model of systemic sclerosis was employed and the gelatinolytic activity of gelatinases was evaluated on the fibrotic tissues of this model. Two groups of ten mice were considered in this work: a group of systemic sclerosis model and control group. For the generation of systemic sclerosis model, mice received bleomycin, while the control group was subjected to phosphate buffered saline (PBS) reception. Mice were tested for fibrosis by using trichrome staining, hydroxyproline measurement and α-SMA detection in tissue sections. Additionally, the gelatinolytic activity of matrix metalloproteinase 2 and matrix metalloproteinase 9 were measured using gelatin zymography in lungs and skin tissue homogenates. The obtained results indicated that subcutaneous injection of bleomycin-induced fibrosis in skin and lung tissues of mice. Pro and active forms of matrix methaloproteinase 9 were increased in fibrotic lung tissues (p<0.05 and p<0.01, respectively), while, the gelatinolytic activity of MMP2 was unaffected in these tissues. Additionally, in skin tissues of bleomycin-treated animals, both pro and active forms of MMP9 and MMP2 were increased (p<0.05). Pro and active forms of gelatinases increase differently in skin and lung tissues of bleomycin-induced scleroderma.  

scholarly journals Matrix metalloproteinases 2 and 9 activity after intra-articular injection of autologous platelet-rich plasma for the treatment of osteoarthritis in dogs

2018 ◽  
Vol 87 (2) ◽  
pp. 127-135 ◽  
Author(s):  
Mustafa Arican ◽  
Atilla Şimşek ◽  
Kurtuluş Parlak ◽  
Kamil Atli ◽  
Gonca Sönmez
Keyword(s):  
Synovial Fluid ◽  
Matrix Metalloproteinase ◽  
Platelet Rich Plasma ◽  
Gelatin Zymography ◽  
Brief Pain Inventory ◽  
Experimental Period ◽  
Matrix Metalloproteinase 2 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Metalloproteinase 9

Intra-articular injection of platelet-rich plasma offers a promising potential for treatment of osteoarthritis in dogs. Twenty dogs weighing 25 to 50 kg (mean 38 kg) with unilateral stifle osteoarthritis were used for the study. Fourteen dogs were given intra-articular platelet rich plasma treatment and 6 dogs were used as controls. Double centrifuge method was used to obtain platelet-rich plasma. Radiography and ultrasonography of the affected joint were carried out and scores for lameness severity and pain severity were assigned by the attending clinicians. Synovial fluid was collected under sterile conditions at pre-treatment and on the 1st, 3rd, 5th, 7th, 15thdays, and 4, 8 and 12 weeks after treatment. Gelatin zymography and Enzyme-linked Immunosorbent Assay were used to determine the synovial fluid levels of matrix metalloproteinase-2 (MMP-2) and metalloproteinase-9 (MMP-9). No adverse effects associated with the injection of the platelet concentrate or saline were observed. Hudson Visual Analog Scale and Canine Brief Pain Inventory scores for all components were non-significantly different between weeks 0, 4, 12 for control dogs. Matrix metalloproteinase-9 was totally and MMP-2 was partially inhibited in the platelet-rich plasma group. In the control group, MMP-9 was partially inhibited during the first month and activation started later. Matrix metalloproteinase-2 was constant in control samples throughout the experimental period. Platelet-rich plasma is a safe and effective method for treatment of dogs with osteoarthritis, possibly more useful for early cases with mild and moderate osteoarthritis. It is suggested that plasma rich platelet should be injected several times at regular intervals instead of a single application.

The analysis of surface saccharide profiles through fluorescein-labelled lectins in a rat pancreatic tissue with established metabolic syndrome model

2018 ◽  
Vol 44 (1) ◽  
pp. 98-104
Author(s):  
Yosun Mater ◽  
Sule Beyhan-Ozdas
Keyword(s):  
Metabolic Syndrome ◽  
Metabolic Diseases ◽  
Pancreatic Tissue ◽  
Control Group ◽  
High Fructose Diet ◽  
Tissue Sections ◽  
Membrane Surfaces ◽  
High Fructose ◽  
A Cell ◽  
And Control

Abstract“Glycans”, which are generally referred as oligosaccharides and polysaccharides, are structures that are present on all cellular surfaces with proteins and lipids being attached to their basic chain structures. Many studies in the field of glycobiology have identified the various and complicated biological roles of these glycans which make them perfect molecules to use in labelling and selecting body cells specifically. This study aims at analyzing the modifications in saccharide units of glycans on a cell membrane surfaces of the pancreatic tissue of rats to which normal and metabolic syndrome (MetS) are established. To this end, a MetS model was created through a high fructose diet in Spraque Dawley breed of rats and the pancreatic tissue sections of the group with MetS and control group animals were evaluated comparatively. The targeted saccharide units were examined with Fluorescent Microscope by using two different Fluorescein (FITC) labelled lectins, namely Maackia amurensis-1 lectin [FITC-(MAL-I)] and the Wheat Germ Agglutinin (FITC-WGA). It was observed that FITC-MAL-1-labelled Galβ4GlcNAc units did not change much due to high- fructose diet. On the other hand, more GlcNAc, Neu5Ac and β-GlcNAc units which are labelled with FITC-WGA lectin increase in numbers in pancreatic sections of high fructose diet, compared to control group. Thus, a rapid and specific labelling method, which can identify surface saccharide sequences specifically, was developed. The method can be used in early diagnosis and/or treatment for metabolic diseases.

scholarly journals Lidocaine Alleviates Sepsis-Induced Acute Lung Injury in Mice by Suppressing Tissue Factor and Matrix Metalloproteinase-2/9

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Binbin Zheng ◽  
Hongbo Yang ◽  
Jianan Zhang ◽  
Xueli Wang ◽  
Hao Sun ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Matrix Metalloproteinase ◽  
Gelatin Zymography ◽  
Neutrophil Infiltration ◽  
Negative Regulator ◽  
Matrix Metalloproteinase 2 ◽  
Cytokine Signaling

Acute lung injury (ALI) is one of the fatal symptoms of sepsis. However, there were no effective clinical treatments. TF accumulation-induced fibrin deposit formations and coagulation abnormalities in pulmonary vessels contribute to the lethality of ALI. Suppressor of cytokine signaling 3 (SOCS3) acts as an endogenous negative regulator of the TLR4/TF pathway. We hypothesized that inducing SOCS3 expression using lidocaine to suppress the TLR4/TF pathway may alleviate ALI. Hematoxylin and eosin (H&E), B-mode ultrasound, and flow cytometry were used to measure the pathological damage of mice. Gelatin zymography was used to measure matrix metalloproteinase-2/9 (MMP-2/9) activities. Western blot was used to assay the expression of protein levels. Here, we show that lidocaine could increase the survival rate of ALI mice and ameliorate the lung injury of ALI mice including reducing the edema, neutrophil infiltration, and pulmonary thrombosis formation and increasing blood flow velocity. Moreover, in vitro and in vivo, lidocaine could increase the expression of p-AMPK and SOCS3 and subsequently decrease the expression of p-ASK1, p-p38, TF, and the activity of MMP-2/9. Taken together, our study demonstrated that lidocaine could inhibit the TLR4/ASK1/TF pathway to alleviate ALI via activating AMPK-SOCS3 axis.

scholarly journals Kallikrein‐1 Blockade Inhibits Aortic Expansion in a Mouse Model and Reduces Prostaglandin E2 Secretion From Human Aortic Aneurysm Explants

2021 ◽  
Vol 10 (5) ◽  
Author(s):  
Corey S. Moran ◽  
Erik Biros ◽  
Smriti M. Krishna ◽  
Susan K. Morton ◽  
Daniel J. Sexton ◽  
...  
Keyword(s):  
Aortic Aneurysm ◽  
Mouse Model ◽  
Matrix Metalloproteinase ◽  
Cyclooxygenase 2 ◽  
Matrix Metalloproteinase 2 ◽  
Prostaglandin E ◽  
Blocking Antibody ◽  
Active Matrix ◽  
Suprarenal Aorta ◽  
Metalloproteinase 9

Background Abdominal aortic aneurysm (AAA) is an important cause of mortality in older adults. The kinin B2 receptor agonist, bradykinin, has been implicated in AAA pathogenesis through promoting inflammation. Bradykinin is generated from high‐ and low‐molecular‐weight kininogen by the serine protease kallikrein‐1. The aims of this study were first to examine the effect of neutralizing kallikrein‐1 on AAA development in a mouse model and second to test how blocking kallikrein‐1 affected cyclooxygenase‐2 and prostaglandin E 2 in human AAA explants. Methods and Results Neutralization of kallikrein‐1 in apolipoprotein E‐deficient ( ApoE −/− ) mice via administration of a blocking antibody inhibited suprarenal aorta expansion in response to angiotensin (Ang) II infusion. Kallikrein‐1 neutralization decreased suprarenal aorta concentrations of bradykinin and prostaglandin E 2 and reduced cyclooxygenase‐2 activity. Kallikrein‐1 neutralization also decreased protein kinase B and extracellular signal‐regulated kinase 1/2 phosphorylation and reduced levels of active matrix metalloproteinase 2 and matrix metalloproteinase 9. Kallikrein‐1 blocking antibody reduced levels of cyclooxygenase‐2 and secretion of prostaglandin E 2 and active matrix metalloproteinase 2 and matrix metalloproteinase 9 from human AAA explants and vascular smooth muscle cells exposed to activated neutrophils. Conclusions These findings suggest that kallikrein‐1 neutralization could be a treatment target for AAA.

scholarly journals Steps involved in activation of the complex of pro-matrix metalloproteinase 2 (progelatinase A) and tissue inhibitor of metalloproteinases (TIMP)-2 by 4-aminophenylmercuric acetate

1995 ◽  
Vol 308 (2) ◽  
pp. 645-651 ◽  
Author(s):  
Y Itoh ◽  
S Binner ◽  
H Nagase
Keyword(s):  
Matrix Metalloproteinase ◽  
Noncovalent Complex ◽  
The Other ◽  
Gelatinolytic Activity ◽  
Matrix Metalloproteinase 2 ◽  
Tissue Inhibitor Of Metalloproteinases ◽  
Tissue Inhibitor ◽  
Sh Group ◽  
Inhibitory Domain ◽  
Interstitial Collagenase

Tissue inhibitor of metalloproteinases (TIMP)-2 forms a noncovalent complex with the precursor of matrix metalloproteinase 2 (proMMP-2, progelatinase A) through interaction of the C-terminal domain of each molecule. We have isolated the proMMP-2-TIMP-2 complex from the medium of human uterine cervical fibroblasts and investigated the processes involved in its activation by 4-aminophenylmercuric acetate (APMA). The treatment of the complex with APMA-activated proMMP-2 by disrupting the Cys73-Zn2+ interaction of the zymogen. This is triggered by perturbation of the proMMP-2 molecule, but not by the reaction of the SH group of Cys73 with APMA. The ‘activated’ proMMP-2 (proMMP-2*) formed a new complex with TIMP-2 by binding to the N-terminal inhibitory domain of the inhibitor without processing the propeptide. Thus the APMA-treated proMMP-2*-TIMP-2 complex exhibited no gelatinolytic activity. In the presence of a small amount of free MMP-2, however, proMMP-2* in the complex was converted into the 65 kDa MMP-2 by proteolytic attack of MMP-2, but the complex did not exhibit gelatinolytic activity. The gelatinolytic activity detected after APMA treatment was solely derived from the activation of free proMMP-2. The removal of the propeptide of the proMMP-2* bound to TIMP-2 was also observed by MMP-3 (stromelysin 1), but not by MMP-1 (interstitial collagenase). MMP-3 cleaved the Asn80-Tyr81 bond of proMMP-2*. On the other hand, when MMP-3 was incubated with the proMMP-2-TIMP-2 complex, it bound to TIMP-2 and rendered proMMP-2 readily activatable by APMA. These results indicate that the blockage of TIMP-2 of the complex with an active MMP is essential for the activation of proMMP-2 when it is complexed with TIMP-2.

Expression of Vascular Endothelial Growth Factor, Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9 in Polycystic Ovarian Syndrome Rats and Its Implication

2021 ◽  
Vol 11 (5) ◽  
pp. 841-846
Author(s):  
Wei Li ◽  
Yufang Zhang ◽  
Fuping Li ◽  
Yufen Shi ◽  
Yan Wang
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Matrix Metalloproteinase ◽  
Polycystic Ovary ◽  
Ovarian Tissue ◽  
Matrix Metalloproteinase 2 ◽  
Control Group ◽  
Vaginal Smear ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Polycystic ovary syndrome (PCOS) is a female endocrine disorder and frequently leads to infertility. Vascular endothelial growth factor (VEGF) has crucial roles and matrix metalloproteinase (MMPs) is correlated with cell migration. Both of them are involved in the occurrence and progression of PCOS. This study established a rat PCOS model using letrozole to measure the expression of VEGF, MMP-2 and MMP-9 (MMP-2/9), to analyze its correlation with PCOS. Letrozole was applied by gavage to establish rat PCOS model. General condition and ovarian tissue morphology were observed under a light field microscope. ELISA and immunohistochemistry (IHC) were used to detect serum or tissue expression of VEGF, MMP-2/9. Estrous cycle of rats was disrupted after 12 d for using letrozole. Vaginal smear showed abundant leukocytes with sparse keratinocytes. Ovary showed whitening and increased volume, with early phase small follicles plus lower granular cells or corpus luteum. Compared to control group, experimental group had significantly higher VEGF, MMP-2/9 (P < 0.05), which were higher in antral follicles than those in preantral follicle with higher expressions than primordial follicle (P < 0.05). In conclusion, VEGF, MMP-2/9 are abundantly expressed in both serum and tissues of PCOS rats.

Grifolin Inhibits Proliferation, Migration, and Invasion of Lung Cancer A549 Cells by Regulating miRNA-1251-5p

2020 ◽  
Vol 12 (3) ◽  
pp. 376-382
Author(s):  
Xiao Liu ◽  
Yuanlan Chen ◽  
Zhijiao Jiang
Keyword(s):  
Lung Cancer ◽  
Matrix Metalloproteinase ◽  
Cellular Proliferation ◽  
A549 Cells ◽  
Matrix Metalloproteinase 2 ◽  
Migration And Invasion ◽  
Control Group ◽  
Inhibitory Influence ◽  
Proliferation Inhibition ◽  
Inhibition Rate

To investigate the effect and molecular mechanism of grifolin on the proliferation, transfer, and infiltration of lung cancer (LC) cells. A control group, low grifolin group, midium grifolin group and high grifolin group, anti-miRNA-NC group, anti-miRNA-1251-5p group, grifolin + miRNA-NC group, and grifolin + miRNA-1251-5p group were established based on LC A549 cells. MTT was employed to detect cellular proliferation inhibition rate; Transwell assay was used to detect cellular transfer and infiltration; Western blot was used to test Cyclin D1, cyclin-dependent kinase inhibitor 1A (p21), matrix metalloproteinase 2 (MMP-2), and matrix metalloproteinase 9 (MMP-9) protein expression; and finally RT-qPCR was employed to test miRNA-1251-5p expression. After treatment with different concentrations of grifolin, an increase in proliferation inhibition rate of A549 cells, a decrease in migrating and invading cells, a decrease in CyclinD1, MMP-2, and MMP-9 expression, an increase in p21 expression, and a decrease in miRNA-1251-5p expression in a manner of concentration dependence was observed (P < 0.05). Inhibiting miRNA-1251-5p expression led to an increase in cellular proliferation inhibition rate, a decrease in migrating and invading cells, a decrease in CyclinD1, MMP-2, and MMP-9 expression, and an increase in p21 expression (P < 0.05). Overexpression of miRNA-1251-5p reversed the inhibitory influence of grifolin on the proliferation, transfer, and infiltration of A549 cells. Grifolin likely inhibits the proliferation, transfer, and infiltration of LC A549 cells by down-regulating miRNA-1251-5p.

scholarly journals Anti-endometriotic effect of Angelica sinensis (Oliv.) Diels extract in human endometriotic cells and rats

2020 ◽  
Vol 19 (4) ◽  
pp. 817-821
Author(s):  
Qi-Xiang Xiong ◽  
Xiao-Yun Ruan ◽  
Al-Ping Deng ◽  
Jue Liu ◽  
Qing Zhou
Keyword(s):  
Matrix Metalloproteinase ◽  
Female Rats ◽  
Matrix Metalloproteinase 2 ◽  
Inflammatory Factors ◽  
Ca 125 ◽  
Angelica Sinensis ◽  
Control Group ◽  
High Dose ◽  
Cancer Antigen ◽  
Tnf Α

Purpose: To study the anti-endometriotic effect of Angelica sinensis (Oliv.) Diels extract (ASDE) in human endometriotic cells and rats.Method: Forty female rats were randomly divided into four groups (10 rats/group): control, endometriosis+danazol, endometriosis+high dose of ASDE and low dose of ASDE. The rats were orally administered either vehicle (200 μL of PBS) alone or ASDE (140, 280 and 560 mg/kg/day) for 5 weeks. Danazol was used as the control drug. After induction of endometriosis for 4 weeks, the rats were sacrificed by cervical dislocation and the peritoneum and visceral organs examined visually to measure the number of endometriotic lesions. Serum levels of cancer antigen 125 (CA-125) and interleukin 13 (IL-13), interleukin 18 (IL-18) and tumor necrosis factor-alpha (TNF-α) of peritoneal fluids of rats were measured using ELISA kits. Western blot assay was performed to measure the levels of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9)  expressions after 24 h of treatment with ASDE (30, 60, and 120 μg/mL).Results: ASDE-treated rats displayed reduced numbers of total endometriotic lesions when compared with vehicle-treated controls (p < 0.01). When the rats were treated with high dose of ASDE, serum CA-125 level, as well as IL-18 and TNF-α levels in peritoneal fluids were significantly lower than that of the control group (p < 0.01); however, IL-13 level in peritoneal fluids was significantly higher than that of the control group (p < 0.01). ASDE treatment significantly suppressed the levels of MMP-2 and MMP-9 protein in 11Z cell (p < 0.01).Conclusion: The results reveal that ASDE exhibits significant anti-endometriotic effect by inhibiting inflammatory factors in rats. Thus, the plant extract can potentially be developed for the clinical management of endometriosis. Keywords: Angelica sinensis, Endometriosis, Cancer antigen, Endometriotic lesions, Matrix metalloproteinase

scholarly journals Regulation of microRNA-33, SREBP and ABCA1 genes in a mouse model of high cholesterol

2021 ◽  
Vol 64 (1) ◽  
pp. 103-108
Author(s):  
Xianglun Zhang ◽  
Hongbo Zhao ◽  
Qingkai Sheng ◽  
Xiaomu Liu ◽  
Wei You ◽  
...  
Keyword(s):  
Mouse Model ◽  
Cholesterol Homeostasis ◽  
Disease Assessment ◽  
Control Group ◽  
High Cholesterol ◽  
Regulate Gene Expression ◽  
Muscle Tissues ◽  
Potential Biomarker ◽  
Artery Disease ◽  
And Control

Abstract. MicroRNAs are short non-coding RNAs that regulate gene expression. Several microRNAs, useful for coronary artery disease assessment, have previously been identified. MicroRNA-33 is located within SREBP introns and controls cholesterol homeostasis. In order to find the possibility of microRNA-33 as a potential biomarker in high cholesterol disease, we developed a mouse model for coronary heart disease by feeding mice with a high-fat diet. The expression differences of microRNA-33, SREBP and ABCA1 genes in the liver, muscle, and lipid tissues were compared between a high-cholesterol group and control group in mice. The results showed that ABCA1 was up-regulated by high cholesterol conditions in liver, muscle and lipid tissues. SREBP1C was up-regulated by high cholesterol conditions in the liver and lipid tissues and down-regulated by high cholesterol conditions in the muscle tissue. MicroRNA-33 and SREBP2 were down-regulated by high cholesterol conditions in the liver and muscle tissues and up-regulated by high cholesterol conditions in the lipid tissue. Our study suggests that antisense therapeutic targeting of microRNA-33 may be a potential biomarker for cardiovascular disease.

scholarly journals Effect of early body cavity continuous circulation hyperthermia perfusion chemotherapy combined with systemic chemotherapy (and nursing) on survival rate and serum tumor markers in patients with advanced gastric cancer

2020 ◽  
Vol 18 ◽  
pp. 205873922094233
Author(s):  
Xia Liu ◽  
Miao Tang
Keyword(s):  
Survival Rate ◽  
Matrix Metalloproteinase ◽  
Tumor Markers ◽  
Systemic Chemotherapy ◽  
Matrix Metalloproteinase 2 ◽  
Control Group ◽  
Study Group ◽  
Term Survival ◽  
Serum Tumor Markers ◽  
Significant Difference

This study was designed to investigate the effects of early coelom continued circulatory hyperthermic perfusion chemotherapy combined with systemic chemotherapy on the survival and serum tumor markers. A total of 128 patients with advanced gastric carcinoma who have received surgical treatments were selected and were randomly divided into study group (receiving early circulatory intraperitoneal hyperthermic perfusion chemotherapy combined with systemic chemotherapy postoperatively) and control group (receiving chemotherapy alone postoperatively), with 64 cases in each. Comparison of serum tumor markers (CA724, CA242), vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), immune function indexes (CD3+, CD4+, CD8+), and 5-year survival rate was assessed. Before treatment, there was no significant difference in the serum tumor markers (CA724 and CA242) as well as the serum VEGF, MMP-2, and MMP-9 levels among the two groups ( P > 0.05). However, the above parameters in the study group were significantly lower than control group 8 weeks after the treatment ( P < 0.05). Before treatment, there was no significant difference in CD3+, CD4+, CD8+ and CD4+/CD8+ between the two groups ( P > 0.05). Eight weeks after the treatment, the CD3+, CD4+ and CD4+/CD8+ in the study group were significantly higher than those in the control group ( P < 0.05), while the CD8+ levels was significantly lower than the latter group ( P < 0.05). The 2-year recurrence rate in the study group was lower than the control group ( P < 0.05). Furthermore, survival rates (1-year, 3-year and 5-year) of the study group were all higher than control group ( P < 0.05). Early circulatory hyperthermia perfusion chemotherapy combined with systemic chemotherapy contributed to the decrease in the serum tumor markers (CA724, CA242) as well as the serum VEGF, MMP-2, and MMP-9 levels, improved the immune functions. This therapeutic regimen prolonged the long-term survival conditions of the patients as well as proved the safety and effectiveness.

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