Effect of ANKRD49 on migration of human lung adenocarcinoma cells and its mechanism / 中国生物制品学杂志

@#Objective To study the effect of ankyrin repeat domain 49(ANKRD49)on the migration of human lung adenocarcinoma cell line NCI-H1299 and its mechanism.Methods NCI-H1299 cells were infected with lentivirus vector carrying ANKRD49 gene and shRNA targeting ANKRD49 to construct the cell models stably overexpressing and knocking down ANKRD49. Meanwhile,the control cell models infected with empty lentivirus vector and lentivirus vector with scramble sequences were constructed respectively. The expression levels of ANKRD49 mRNA and protein were detected by real-time fluorescence quantitative PCR and Western blot. The effect of ANKRD49 on cell migration was measured by scratch test. The mRNA and protein levels of matrix metalloproteinase(MMP)-2/9 and tissue inhibitor of metalloproteinase(TIMP)-1/2 were detected by real-time fluorescence quantitative PCR and Western blot. The protein expression levels of p65,p-p65,IκBα and p-IκBα were detected by Western blot.Results The levels of ANKRD49 mRNA and protein in the ANKRD49 overexpression group were significantly higher than those in the control group(t = 70. 02 and 45. 68,respectively,each P < 0. 001). Compared with the control group,the migration ability of cells in the ANKRD49 overexpression group significantly increased at 24 h and 48 h(t = 5. 343 and 3. 282,P = 0. 005 9 and 0. 030 4,respectively);The mRNA transcription levels and protein expression levels of MMP-2 and MMP-9 significantly increased(t = 9. 304 and 6. 193,P =0. 000 7 and 0. 003 5,respectively),while the mRNA and protein expression of TIMP-1 and TIMP-2 decreased significantly(t = 3. 858 and 3. 517,P = 0. 018 2 and 0. 024 5,respectively),and the values of MMP-2/TIMP-1 and MMP-9/TIMP-2 significantly increased(t = 17. 7 and 9. 682,P < 0. 001 and < 0. 01,respectively);The expression of p-p65 and pIκBα significantly increased,the total protein levels of p65 and IκBα showed no obvious change,and the values of p-p65/p65 and p-IκBα/IκBα significantly increased(t = 3. 962 and 5. 370,P = 0. 016 7 and 0. 005 8,respectively). However,knocking down of ANKRD49 presented the opposite results.Conclusion ANKRD49 promotes the migration of NCI-H1299cells by enhan-cing the expression of MMP-2/9,the values of MMP-9/TIMP-1 and MMP-2/TIMP-2 via activating NF-κB/p65 signa-ling pathway.

Effects of miR-143 on the migration and invasion of osteosarcoma cells by regulating MMP-13 expression / 中国骨伤

OBJECTIVE@#To explore the effect of miR-143 regulating matrix metalloproteinase(MMP)-13 expression on migration and invasion of osteosarcoma cells.@*METHODS@#The mouse osteosarcoma cell line 143B cells were cultured in 96-well plates, and blank group, negative group, positive group, and intervention group were set up. Then, the blank group did no treatment 50 μg miR-143 mimic was added to positive group, negative group added equal mimic NC (control sequence of miR-143 mimic), the intervention group was added 50 μg miR-143 mimic and 10 μg MMP-13 protein, all groups continued to culture for 3 to 6 hours, and finally the serum was aspirated to treat for half an hour. The protein expressions of miR-143 and MMP-13 in each group were measured by fluorescence quantitative PCR experiment and Western blot experiment, respectively, and the invasion and migration abilities of cells were measured by Transwell and scratch experiments.@*RESULTS@#The expression of MMP-13 protein in the positive group and the intervention group was significantly lower than that in the blank group, and the positive group was lower than the intervention group (P<0.05);The mean numbers of invasive cells in blank group, negative group, positive group and intervention group were (1 000.01±44.77), (959.25±46.32), (245.04±4.33), (634.06±33.78) cells/field, respectively;the scratch healing rate of the positive group and the intervention group was significantly lower than that of the blank group, and the positive group was lower than the intervention group (P<0.05).@*CONCLUSION@#MMP-13 is a target of miR-143, which can reduce the migration and invasion ability of osteosarcoma cells by inhibiting the expression of MMP-13.

Inhibition of cell proliferation and migration by Oroxylum indicum extracts on breast cancer cells via Rac1 modulation / 药物分析学报

In this study, we investigated how Oroxylum indicum leaf and fruit extracts affect the viability and migration of MCF-7 breast cancer cells and the mechanisms of action responsible for these effects. MCF-7 cells treated with the extracts were examined using the sulforhodamine B, colony formation and caspase 3 activity assays, and by Western blotting. O. indicum extracts were found to inhibit MCF-7 cell growth in a concentration-and time-dependent manner, with 48 h IC50 values of 57.02 ± 2.85μg/mL and 131.3 ± 19.2μg/mL for leaf and fruit extracts, respectively. Further, the O. indicum leaf extract caused a reduction in MCF-7 cell viability, induction of MCF-7 cell apoptosis and ROS formation, and an increase in caspase 3 activity. Also, the two extracts inhibited MCF-7 cell migration and reduced both MMP 9 and ICAMP1 gene expression and MMP9 protein expression. Additionally, O. indicum extracts greatly reduced expression of the cell cycle regulatory protein Rac1 in the mevalonate pathway. In summary, O. indicum leaf and fruit extracts reduce breast cancer cell growth, cell viability and cell migration. O. indicum constituents could, therefore, be useful for augmenting the activity of chemotherapeutic drugs employed to treat breast cancer.

Expressions of matrix metalloproteinases and their inhibitors in steroid-induced necrosis of rat femoral head / 西安交通大学学报(医学版)

Objective To study the protein expression levels of matrix metalloproteinases (MMPs)and their inhibitors in bone tissues of rat femoral head and to explore the relationship between necrosis of femoral head and glucocorticoid.Methods Twenty healthy adult SD rats were randomly divided into glucocorticoid group and control group,with 10 rats in each.Glucocorticoid group was treated with intramuscular injection of hydrocortisone twice a week.The control group received normal saline of the same volume.Four weeks later,bone tissues of left femoral head were collected from each group of rats for HE determination of femoral head necrosis.The expressions of matrix metalloproteinase-1 (MMP-1 ), matrix metalloproteinase-2 (MMP-2 ), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1 ),and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2 )at mRNA and protein levels were detected by RT-PCR and Western blot techniques,respectively.Results The expressions of MMP-1 and MMP-2 at mRNA and protein levels were higher in glucocorticoid group than those in the control group. However,TIMP-1 and TIMP-2 gene and protein expression levels were lower in glucocorticoid group (all P<0.05). Conclusion The expressions of MMPs in bone tissues of rat femoral head in early necrosis were increased,but their inhibitors had decreased expressions. We can draw the conclusion that glucocorticoid-induced necrosis of femoral head may be related to its regulation of the expression levels of MMPs and their related inhibitors.

Effects of PRDX1 gene silencing on invasion and migration of human colorectal cancer SW480 cells / 中国免疫学杂志

Objective:To investigate the effects of RNA interference(RNAi)-mediated silencing of Peroxiredoxin 1(PRDX1)gene on the invasion and migration of human colorectal cancer SW480 cells.Methods: Lentiviruses negative control vector and PRDX1 RNAi were transfected respectively into colorectal cancer SW480 cells.The transfected cells were divided into PRDX1 silencing group(si-PRDX1)and negative control group(Vector).The expressions of PRDX1 mRNA and protein in SW480 cells were exa mined by quantitative real-time PCR(qRT-PCR)and immunoblotting(Western blot),respectively.The cell migration and invasion capabilities were evaluated with transwell chamber assay and transwell chamber,respectively.The protein expressions of TIMP-2,MMP-2 and MMP-9 were detected by Western blot.Results: Compared with control group,the expressions of PRDX1 mRNA and protein were significantly decreased in PRDX1 silencing group(P<0.01),PRDX1 gene silencing cell line was successfully constructed.The levels of invasion and migration capacities of SW480 cells transfected with si-PRDX1 were lower than those in the cells transfected with control-siRNA(vector)(P<0.01).The expression of TIMP-2 was significantly increased,while the expressions of MMP-2 and MMP-9 were significantly decreased(P<0.05).Conclusion: Silencing of PRDX1 inhibits the invasion,migration and metastasis of human colorectal cancer SW480 cells by regulating the expressions of TIMP-2,MMP-2 and MMP-9.

Berberine regulates MMPs/TIMP via inhibition of P38 MAPK/NF-κB phosphorylation and anti-inflammation in rat experimental periodontitis / 西安交通大学学报(医学版)

ABSTRACT:Objective To investigate the effects of berberine on matrix metalloproteinases/tissue inhibitors of matrix metalloproteinases (MMPs/TIMPs) in rat periodontitis .Methods Adult male Sprague‐Dawley rats were subjected to thread ligation and porphyromonas gingivalis ( P . gingivalis ) inoculation resulting in periodontitis . Berberine [150 mg/(kg · d)] or vehicle was administered by oral gavage for 4 weeks .Alveolar bone loss and soft‐tissue destruction were determined by micro‐computed tomography (μ‐CT) and HE staining .The contents of tumor necrosis factor‐α(TNF‐α) and interleukin‐1β(IL‐1β) of gingival tissue were examined by ELISA .The expressions of MMP‐2 ,MMP‐9 and TIMP‐2 as well as the phosphorylation of P38 MAPK and NF‐κB were determined by Western blot .Results Significant increases were observed in alveolar bone loss and periodontal soft‐tissue destruction with higher levels of TNF‐α, IL‐1β and MMP‐2/9 expressions and the activities of P38 MAPK and NF‐κB in the experiment periodontitis group .Berberine of [150 mg/(kg · d)] not only improved the periodontal tissue and decreased alveolar bone loss ,but also reduced the contents of TNF‐α,IL‐1βand MMP‐2/9 and increased TIMP‐2 .In addition ,berberine inhibited the phosphorylation of P38 MAPK/NF‐κB .Conclusion Berberine protects against periodontal tissue damage via decreasing MMP‐2 and MMP‐9 expressions but increasing TIMP‐2 expression , which may be induced by inhibition of P38 MAPK/NF‐κB and the anti‐inflammatory effect on rat periodontitis .

Effect of oxymatrine treatment on the invasion of human cervical cancer cells / 西安交通大学学报(医学版)

Objective To investigate the anticancer effect of oxymatrine on cervical cancer cell line (HeLa). Methods MTT assay was used to detect the anti-proliferative effect of oxymatrine.Transwell chamber was used to detect the anti-metastatic effect of oxymatrine.Real-time PCR was used to detect the mRNA levels of MMP-2 and MMP-9.Western blot was used to detect the protein levels of MMP-2,MMP-9,AKT,p-AKT and GADPH. Results We found that application of oxymatrine significantly inhibited the growth of HeLa cells at the concentration above 0.8 mg/mL.We also found that oxymatrine (0.1,0.2 and 0.4 mg/mL)inhibited the invasion of HeLa cells under cytotoxic dose,which was (77.07±20.43)%,(53.95±18.17)% and (20.35±11.20)% of cells that migrated through the matrigel when compared with those of non-oxymatrine treatment group (P<0 .0 5 ). Further research found that oxymatrine (0.1,0.2 and 0.4 mg/mL)could reduce the expression of MMP-2 at the mRNA level,i.e.(82.76±8.71)%,(39.51±12.79)% and (21.53±5.38)% of the expression level when compared with that of non-oxymatrine treatment group (P<0 .0 5 ).The protein expression level of MMP-2 in 0 .4 mg/mL group was (64.69 ±16.52)% of non-oxymatrine treatment group (P<0.05).The phosphorylation level of AKT in 0.4 mg/mL group was (41.27±7.13)% of non-oxymatrine treatment group (P<0.05).Conclusion Oxymatrine can inhibit the invasion of HeLa cells by reducing the expression of MMP-2 via inhibiting the activity of AKT signal pathway.All together,our findings bring new insights into the mechanism of the anticancer effects induced by oxymatrine treatment.

Protective effects of tumor necrosis factor-α blockade by adalimumab on articular cartilage and subchondral bone in a rat model of osteoarthritis

We aimed to investigate the effects of an anti-tumor necrosis factor-α antibody (ATNF) on cartilage and subchondral bone in a rat model of osteoarthritis. Twenty-four rats were randomly divided into three groups: sham-operated group (n=8); anterior cruciate ligament transection (ACLT)+normal saline (NS) group (n=8); and ACLT+ATNF group (n=8). The rats in the ACLT+ATNF group received subcutaneous injections of ATNF (20 μg/kg) for 12 weeks, while those in the ACLT+NS group received NS at the same dose for 12 weeks. All rats were euthanized at 12 weeks after surgery and specimens from the affected knees were harvested. Hematoxylin and eosin staining, Masson's trichrome staining, and Mankin score assessment were carried out to evaluate the cartilage status and cartilage matrix degradation. Matrix metalloproteinase (MMP)-13 immunohistochemistry was performed to assess the cartilage molecular metabolism. Bone histomorphometry was used to observe the subchondral trabecular microstructure. Compared with the rats in the ACLT+NS group, histological and Mankin score analyses showed that ATNF treatment reduced the severity of the cartilage lesions and led to a lower Mankin score. Immunohistochemical and histomorphometric analyses revealed that ATNF treatment reduced the ACLT-induced destruction of the subchondral trabecular microstructure, and decreased MMP-13 expression. ATNF treatment may delay degradation of the extracellular matrix via a decrease in MMP-13 expression. ATNF treatment probably protects articular cartilage by improving the structure of the subchondral bone and reducing the degradation of the cartilage matrix.

Variations in Matrix Metalloproteinase Expression by Disc Location in Patients with Sequestrated Lumbar Disc Herniation

STUDY DESIGN: In vivo study OBJECTIVES: To evaluate variations in matrix metalloproteinase (MMP) expression levels according to the disc location in patients with sequestrated lumbar disc herniation. SUMMARY OF LITERATURE REVIEW: MMPs are considered to be the major catabolic enzymes in the intervertebral disc. MMPs have been known to be the primary mediators of extracellular matrix (ECM) degradation, to play major roles in disc degeneration by changing the collagens and the extracellular matrix, and to be involved in the processes of apoptosis and autoresorption of herniated disc materials by inducing inflammatory cytokines. MATERIALS AND METHODS: The sequestered and contained disc materials were removed from seven patients with sequestered lumbar disc herniations. The materials from the contained discs were classified into group 1 and those of the sequestered discs into group 2. Immunochemistry tests were conducted for the tissues of both groups. The expression levels of MMP-1, 3, and 13 were checked using a fluorescence microscope. The amount of expression of each MMP was calculated using the percentage of expressed cells and analyzed statistically. RESULTS: In the histological study, increased expression of MMP-1, 3, and 13 was found in group 2. In the statistical analysis after the quantification of MMP expression, the expression of all MMPs was found to have increased significantly in group 2 (p<0.05). CONCLUSIONS: The increased expression of MMP-1, 3, and 13 indicated that the inflammation and degeneration processes, and the spontaneous resorption by the surrounding tissues were more active in the sequestered disc group than in the contained disc group.

Intermittent Cold Stress Reducing the Collagen Content of Atherosclerotic Plaque in Experimental ApoE-/-Mice / 中国循环杂志

Objective: To investigate the influence of intermittent cold stress on collagen content of atherosclerotic plaque in experimental ApoE-/-mice. Methods: A total of 20 male ApoE-/-mice at 8 weeks of age were divided into 2 groups:Experimental group, the mice had intermittent cold exposure at (4 ± 1)°C from 8am to 12noon and Control group, the mice were living at (24 ± 2) °C. All animals were treated for 12 weeks, n=10 in each group. The collagen content of atherosclerotic plaque at the aortic root in ApoE-/-mice was observed by Masson staining, the protein expressions of aortic MMP-2, MMP-9 and TIMP-1 were examined by Western blot analysis. Results: Compared with Control group, the Experimental group presented the lower collagen content of atherosclerotic plaque at the aortic root, higher protein expressions of MMP-2, MMP-9 and lower protein expression of TIMI 1. Conclusion: Intermittent cold stress may disturb the balance of MMP/TIMP and decrease collagen content of atherosclerotic plaque to form vulnerable plaque in experimental ApoE-/-mice which may cause acute coronary syndrome.

Expressions of MMP2,COX-2,VEGF and MVD in papillary thyroid carcinoma and their clinical significance / 西安交通大学学报(医学版)

Objective To investigate the expressions of cycloxygenase-2 (COX-2 ),vascular endothelial growth factor (VEGF),matrix metalloproteinase (MMP2 )and micro-vessel density (MVD)in papillary thyroid carcinoma (PTC)and the relationship between their expressions and clinicopathological features,so as to evaluate the malignancy and prognosis of PTC.Methods The expressions of COX-2,MMP2 and VEGF and MVD count in 32 cases of PTC and 18 cases of normal thyroid tissues were detected by immunohistochemical staining.Their relationship with clinicopathological characteristics was analyzed.Results ① The expression of COX-2,MMP2, VEGF and MVD in PTC was as follows:M(Q 3 -Q 1 )=5(1),M(Q 3 -Q 1 )=5.5(2),M(Q 3 -Q 1 )=5.5(1)and M (Q 3 -Q 1 )= 28 (5.75 ),respectively.It differed significantly from that in control group (P 0.5).Conclusion The high expressions of COX-2, VEGF and MMP2 in thyroid tissues may result in the occurrence of PTC and lymph node metastasis,which is related to the regulation of tumor new vessels.Detecting these expressions are of value in evaluating the malignancy and prognosis of PTC.

APRIL mediates migration and invasion of colorectal cancer cells via regulation of matrix metalloproteinases / 中华微生物学和免疫学杂志

Objective To investigate the effects of a proliferation-inducing ligand(APRIL) on migration and invasion of colorectal cancer (CRC) and matrix metalloproteinases (MMPs) expression in order to observe the role of APRIL in CRC metastasis.Methods The siRNA plasmid vector targeting APRIL gene (siRNA-APRIL) was transfected into SW480 cells and recombinant human APRIL(rhAPRIL) was used to stimulate HCT-116 cells.Tumor cell migration and invasion were measured by Transwell chambers.RT-PCR and ELISA were applied to examine the expression level of MMPs.Results Metastatic and invasive capacities of siRNA-APRIL transfected SW480 were significantly inhibited,and these capacities of APRIL stimulated HCT-116 cells were significantly enhanced compared with their respective controls( all P＜0.05 ),accompanied with the alterations of MMPs mRNA and secreted protein expression( P＜0.05).The number of invading cells of SW480 control and rhAPRIL stimulated HCT-116 was significantly decreased by a MMP inhibitor GM6001 ( P＜0.05 ).Conclusion APRIL facilitates migration and invasion of CRC via regulation of MMPs,which suggests that APRIL might be used as a new target for the intervention and treatment of CRC metastasis.

Effect of Haobie Yangyin Ruanjian Decoction on rats with hepatic fibrosis induced by CCl4 composited factor / 中草药

Objective: To observe the effect of Haobie Yangyin Ruanjian Decoction (HYRD) on rats with hepatic fibrosis induced by CCl4 composited factor. Methods: Wistar rats were randomly divided into seven groups: control group, model group, HYRD groups of low, medium, and high doses, positive groups of Fufang Biejia Rungan Tablets, and colchicin. Model of hepatic fibrosis was induced by CCl4 composited factor. Malondialdehyde (MDA), total protein (TP), albumin (ALB) in serum and hydroxyproline (Hyp) in liver were detected by chromatometry; MMP-2 and MMP-9 activities in liver were detected by gelatin zymography; α-SMA expression in liver was evaluated by immunohistochemical method. Results: MDA in serum and Hyp in liver were decreased gradually in HYRD groups compared with those of model group; TP and ALB in serum were increased gradually in HYRD groups compared with those of model group; MMP-2 activity in liver was decreased in HYRD groups compared with those of model group; MMP9 activity had no significant change in each group and α-SMA expression was decreased gradually in HYRD groups compared with those of model group. Conclusion: HYRD can antagonize the hepatic fibrosis induced by CCl4 composited factor.

Bone Regeneration with MMP sensitive hyaluronic acid-based hydrogel, rhBMP-2 and nanoparticles in rat calvarial critical size defect(CSD) model

As an efficient controlled release system for rhBMP-2, a functional nanoparticle-hydrogel complex, incorporated with matrix metalloproteinase( MMP) sensitive peptide cross-linker, was developed and used as a bone transplant. In vivo bone formation was evaluated by soft x-ray, histology, alkaline phosphatase(ALP) activity and mineral contents analysis, based on the rat calvarial critical size defect(8mm in diameter) model.Significantly, effective bone regeneration was achieved with the rhBMP-2 loaded MMP sensitive hyaluronic acid(HA) based hydrogel- Nanoparticles(NP) complex, as compared to only MMP HA, the MMP HA-NP without rhBMP-2, or even with the rhBMP-2. These improvements included the formation pattern of bone and functional marrow, the degree of calcium quantification, and the ALP activity. These results indicate that the MMP sensitive HA with nano-particle complex can be a promising candidate for a new bone defect replacement matrix, and an enhanced rhBMP-2 scaffold.

Exploration of Variety of Matrix Metalloproteinase 9 and Blood Brain Barrier in Cardiopulmonary Resuscitation Rats / 中山大学学报(医学科学版)

[Objective] To explore the variety of matrix metalloproteinase 9 (MMP9) and blood brain barrier (BBB) in cardiopulmonary resuscitation rats.[Methods] Eighty rats were randomly divided into 2 groups:the sham-operated group (n ＝ 40) and the resuscitation group (n ＝ 40).The two groups were anaesthetized and endotracheally intubated,the resuscitation group was also induced to cardiac arrest by aphysia.Then the rats were put to death and samples were taken at immediate,3 h,9 h,24 h,and 48 h.After that,the expression of MMP9,MMP9 mRNA,water content and Evans blue content in brain tissue were detected.Ultramicrostructure of brain tissue was observed with electron microscope.[Results] Compared to the sham-operated group,at 3 h,9 h,24 h and 48 h,the expression of MMP9 of resuscitation group was significantly changed.MMP9mRNA significantly increased.Water content statistically increased and so was Evans blue content.The change of ultramicrostructure in the resuscitation group at 3 h,9 h,24 h,and 48 h was obvious.[Conclusion] The expression of MMP9 and MMP9mRNA obviously increased in the cerebral ischemia model with CPR rats,and got to peak at 24 h.Water content and Evans blue content in brain tissue obviously increased in the cerebral ischemia model with CPR rats,BBB was destroyed,and the peak was 24 h.The injury of ultramicrostructure of brain tissue with electron microscope was obvious,and the peak was 24 h.

Role of Matrix Metalloproteinases in Degenerative Lumbar Disc; Molecular and Immunohistochemical Study

OBJECTIVE: Little is known about the comprehensive molecular and biological mechanism on the development of the degeneration of the intervertebral disc. Many kinds of matrix metalloproteinase(MMP) initiate the degradation of the extracellular matrix including several kinds of collagens and proteoglycans. We compared molecular and immunohistochemical features of degenerated intervertebral disc and normal counterparts in order to investigate the role of MMP-1, 2, 3, 9. METHODS: We have evaluated MMP-1, 2, 3, 9 expression in 30 surgically resected lumbar disc from degenerative disc disease patients and 5 normal control cases. RT-PCR(reverse transcriptase-polymerase chain reaction) and immunohistochemistry were performed. RESULTS: By RT-PCR, normal tissue samples showed merely scant expression of MMP-1, 2, 3, 9 mRNA, but degenerated disc samples revealed more pronounced expression. mRNA amplifications were detected in 60%, 63.3%, 70%, 53.3% cases. By immunohistochemistry, normal tissue samples showed minimal protein expression of MMP-1, 2, 3, 9, but degenerated disc samples revealed more pronounced expression. Protein expressions were detected in 73.3%, 63.3%, 76.7%, 63.3% cases. Both the mRNA amplification and protein overexpression rates were significantly higher in degenerated disc than in the normal tissue. Concordance between both the mRNA amplification and protein expressions of MMP-1, 3, 9 were not observed, but there is well correlation in MMP-2 expression. CONCLUSION: We concluded that the over-expressions of the MMP-1, 2, 3, 9 may contribute to the development of degeneration of the intervertebral disc.

Role of Synovial Fibroblasts in Rheumatoid Arthritis / 한양의대학술지

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial tissue proliferation with progressive joint destruction. The etiology of RA remains unknown, but many factors, including autoimmunity, cytokines and genetic factors, participate in its pathogenesis. There is growing evidence that activated fibroblast like synoviocytes (FLS), as part of a complex cellular network, play an important role in the pathogenesis of RA. It has been understood that proinflammatory cytokines secreted from macrophages and lymphocytes may influence the activation of FLS, but invasive and aggressive behaviour of RA-FLS maintained even in the absence of inflammatory stimuli. This kind of partial transformation is characterized by alterations in the expression of regulatory genes such as p53 and signaling cascade, as well as changes in pathway leading to apoptosis. Under the influences of proinflammatory cytokines in rheumatoid joints, RA-FLS is actively involved in the matrix degradation through the production of matrix metalloproteinases (MMP) and cathepsin. In addition, activated RA-FLS exert specific effects on other cell types such as macrophages and lymphocytes. While careful mapping of cytokine networks a decade ago led to the successful development of anti-cytokine therapy, the elucidation of gene mutations and detailed signaling transduction pathways that are specific to RA as well as mechanisms of action of MMP may provide the new targets for novel therapeutic interventions for RA.

The effect of periodontal flap surgery on Matrix metalloproteinases (MMPs) and Tissue inhibitors of matrix metalloproteinase-1 (TIMP-1) levels in gingival crevicular fluids of periodontitis patients / 대한치주과학회지

No abstract available.

Effect of hyperbric oxygen on infarct volume and matrix metalloproteinase after permanent focal cerebral ischemia in adult rats / 中国康复理论与实践

@#ObjectiveTo investigate the effect of hyperbric oxygen (HBO) on infarct volume and relevant mechanism after permanent focal cerebral ischemia in adult rats.MethodsRat model of focal cerebral ischemia induced by intraluminal filament occlusion of middle cerebral artery (MCA) was used. HBO(2.0 ATA) was applied to HBO group. Infarct volume, matrix metalloproteinase 2 (MMP-2) and MMP-9 were detected at 6h, 24h, 48h, 72h,120h and 10d after ischemia.ResultsThe infarct volume obviously decreased at 120h and 10d and expression of MMP-9 lowered at 48—120h in HBO groups. There was no significant change in MMP-2.Conclusion HBO can reduce infarct volume after cerebral ischemia, which may be related to downregulation of MMP-9 levels.

The Effect of Gabexate Mesylate in vivo Model of Intimal Hyperplasia on the Activity of Matrix Metalloproteinase and Proliferation of Smooth Muscle Cell

PURPOSE: Migration and proliferation of vascular smooth muscle cells (VSMCs) are important for neointimal formation after arterial injury. Migration of VSMCs requires the degradation of basement membrane and extracellular matrix surrounding the cell. There is increasing evidence that VSMCs produce extracellular matrix-degradating proteinases, such as matrix metalloproteinases (MMPs) after arterial injury. METHOD: To assess the effect of gabexate mesylate, an MMP inhibitor, in VSMCs proliferation, migration and intimal thickening, the gelatinolytic activity of MMPs and the expression of VSMC alpha-actin mRNA were analyzed in the balloon-injured rat aorta model. Forty male Sprague-Dawley rats, weighing of 250 to 300 g, underwent aortic intimal denudation with a 2 F balloon catheter. The rats were divided into two groups: the control group (n=20: no medication), and the treatment group (n=20: daily intraperitoneal injection of gabexate mesylate (5.0 mg/kg)). The aorta was harvested at various time intervals, 1, 5, 7, and 21 days after the injury. MMP expression was analyzed by using gelatin zymography, the VSMC alpha-actin mRNA expression was analyzed by RT-PCR, and the intima to media area ratio (IMAR) were evaluated microscopically. RESULT: The treatment group showed significant suppression of intimal hyperplasia compared to the control group on day 21 (P<0.05). Mean IMAR on day 21 were 1.18+/-0.2 in the control group and 0.61+/-0.06 in the treatment group. The gelatinolytic activity of MMP-9 on day 1 after injury was significantly lower in the treatment group compared to the control group (P<0.05). The gelatinolytic activity of activated MMP-2 on days 5, 7, and 21 after injury, decreased significantly in the treatment group compared to the control group (P<0.05). The expression of VSMC alpha-actin mRNA increased on days 7 and 21 after injury. Although the expression of VSMC alpha-actin mRNA was lower in the treatment group, it was not statistically significant. CONCLUSION: These results suggest that gabexate mesylate suppresses intimal hyperplasia formation after arterial injury by decreasing activation of MMP.