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Objective:To investigate the expressions of tissue inhibitor of matrix metalloproteinase-1 (TIMP1) and fibronectin 1 (FN1) in pregnancy associated breast cancer (PABC) and their correlations with expression of E-cadherin (E-cad).Methods:The clinicopathological data of 55 PABC patients in Binzhou People's Hospital Affiliated to Shandong First Medical University from January 2011 to December 2020 were retrospectively analyzed. Immunohistochemistry was used to detect expressions of TIMP1, FN1 and E-cad in cancer tissues and corresponding paracancerous tissues (>3 cm from the edge of the tumor foci). The expressions of TIMP1 and FN1 proteins in fresh intraoperative frozen cancer tissues and paracancerous tissues of 10 PABC patients were detected by Western blotting. The correlations of TIMP1 and FN1 expressions with clinicopathological characteristics of patients were analyzed by χ2 test, the correlation of TIMP1 and FN1 expressions with E-cad expression was analyzed by Spearman method, and the correlation of TIMP1 and FN1 expressions with survival was analyzed by Kaplan-Meier method. Results:The positive rates of TIMP1 and FN1 in PABC tissues were 72.7% (40/55) and 58.2% (32/55), and 25.5% (14/55) and 18.2% (10/55) in paracancerous tissues, and the differences were statistically significant ( χ2 values were 24.59 and 18.64, both P < 0.001). The results of Western blotting showed that the relative expressions of TIMP1 and FN1 proteins in the fresh cancer tissues of 10 PABC patients was higher than those in the corresponding paracancerous tissues (1.60±0.76 vs. 0.62±0.29, 1.31±0.62 vs. 0.44±0.15), and the differences were statistically significant ( t values were 5.92 and 4.86, both P < 0.001). The expressions of TIMP1 and FN1 in PABC tissues were correlated with estrogen receptor expression, Ki-67 positivity index, TNM stage and lymph node metastasis (all P < 0.05). The expressions of TIMP1 and FN1 were negatively correlated with expression of E-cad in PABC ( r values were -0.471 and -0.432, both P < 0.001). Five cases were lost to follow-up, and the remaining 50 cases had a median follow-up time of 43 months (12-90 months). Among the 50 cases, 36 cases were TMP1-positive and 29 cases were FN1-positive. The overall survival of TIMP1-negative group and FN1-negative group were better than those of the corresponding positive group ( χ2 values were 4.49 and 6.06, both P < 0.05); the median overall survival time of TIMP1-positive group and FN1-positive group were 51 months (95% CI 37-65 months) and 43 months (95% CI 32-53 months), while that of TIMP1-negative group and FN1-negative group were 89 months (95% CI 84-93 months) and 87 months (95% CI 85-92 months). Conclusions:TIMP1 and FN1 expressions are elevated in PABC tissues and negatively correlated with E-cad expression, TIMP1 and FN1 may be involved in PABC invasion through epithelial-mesenchymal transition and affect the prognosis of patients.
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Objective: To observe the effects of different combinations of Gentianae Macrophyllae Radix (Qinjiao) on the ankle joint matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) of rheumatoid arthritis (RA) model rats with wind-cold-dampness arthralgia.Method: Eighty healthy SD rats were randomly divided into 8 groups, namely blank control group, collage Ⅱ model group, wind-cold-dampness syndrome model group, positive control group, single-taste Gentianae Macrophyllae Radix group, Gentianae Macrophyllae Radix-Clematidis Radix et Rhizoma group (GC group), Gentianae Macrophyllae Radix-Taxilli Herba group (GT group), Gentianae Macrophyllae Radix-Stephanlae Tetrandrae Radix group (GS group), with 10 rats in each group. Rat model of wind-cold-dampness RA was induced through the injection with type Ⅱ collagen emulsion and wind-cold-dampness stimulation. After the establishment of the model, the blank control group, collage Ⅱ model group and wind-cold-dampness syndrome model group were given normal saline, and the corresponding liquid medicine was given to each administration group. In the experiment, the thickness of the left posterior metatarsal of rats was measured every 3 days, and the swelling degree of metatarsal was calculated. The arthritis index (AI) was evaluated on the 38th day of the experiment. The serum rheamatoid factor(RF) content of rats was detected by enzyme linked immunosorbent assay (ELISA). The expressions of MMP-3 and TIMP-1 in ankle joint were detected by Western blot. The expressions of MMP-3 and TIMP-1 mRNA in ankle joint were detected by real-time fluorescence quantitative PCR (Real-time PCR).Result: Compared with the blank group, the swelling degree, AI score, serum RF content, MMP-3 protein expression and MMP-3 mRNA expression in ankle joints of coll age Ⅱ model group and model wind-cold-dampness syndrome group were significantly increased (PPPPPPConclusion: For rheumatoid arthritis with wind-cold-dampness arthralgia, mild and warm traditional Chinese medicine (TCM) has a better effect than the combination of mild and cold TCM or mild TCM drugs. The experimental results are basically consistent with the principle of "treating cold diseases with hot medicine". The mechanism of the compatibility in treating rheumatoid arthritis due to wind-cold-dampness arthralgia may be related to the reduction of MMP-3, the increase of TIMP-1 expression and the reduction of articular cartilage damage.
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Objective To observe the effects of ShenGuiBaoXin decoction on matrix metalloproteinases-2 (MMP-2), the tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), brain natriuretic peptide (BNP) levels, and cardiac histopathology in rats with heart failure, and to investigate the mechanism of the inhibition effect on ventricular remodeling in rats with heart failure. Methods Ninety male SD rats were randomly divided into two groups, with 15 rats in the control group and 75 rats in the model group. Normal saline was injected in the normal control group. The model group was given an intraperitoneal injection of isoprenaline 3 mg/ (kg·d). After 4 weeks, an ejection fraction of ≤50％ on echocardiography was considered a successful model. Seventy-five rats were randomly divided into the model, Qiliqiangxin, and ShenGuiBaoXin groups (high, medium, and low doses), with 15 rats in each group. Eight weeks later, the cardiothoracic ratio and BNP level were measured, hematoxylin-eosin staining was performed, and the MMP-2 and TIMP-1 protein expressions in the myocardium was detected. Results In terms of cardiothoracic ratio and BNP level, all the groups showed decreases after treatment, especially the Qiliqiangxin and high-dose groups. The MMP-2 protein expression level was decreased in all the groups after the treatment, and the high-dose group was superior to the Qiliqiangxin group. Conclusion ShenGuiBaoXin decoction functions by reducing the MMP-2 expression level, regulating MMP-2/TIMP-1 dynamic balance, maintaining the balance of synthesis and degradation of the extracellular matrix, inhibiting ventricular remodeling, and improving cardiac function.
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Objective To observe the effects of prazosin on matrix metalloproteinase‐1(MMP‐1) and tissue inhibitor of met‐alloproteinase 1 (TIMP‐1) expression in atherosclerosis plaque of ApoE knock‐out(ApoE-/- ) mice model and to explore its anti‐atherosclerotic effect and mechanism .Methods Twenty‐four 8‐week‐old ApoE-/- mice were randomly divided into the normal diet group ,high‐fat diet group and prazosin group ,8 cases in each group .The normal diet group was fed by common fodder ,while the high fat group and prazosin group were fed by high fat diet ;on the basis of the high fat diet ,the prazosin group was started to con‐duct gavage of prazosin hydrochloride 1 mg/kg every day ,while the normal diet group and the high fat diet group were daily ga‐vaged by the same volume of normal saline .The abdominal aortic venous blood after 12 weeks in each group was collected for detec‐ting the blood lipid levels .The aorta arterial blood sample was collected for detecting MMP‐1 and TIMP‐1 expression levels by im‐munohistochemistry .Results Compared with the high fat diet group ,the levels of serum TG ,TC and LDL‐C in the prazosin group were significantly decreased ,and the HDL‐C level was increased ,the differences were statistically significant (P< 0 .01 or P<0 .05);the area of aorta arterial atherosclerotic plaque and intima thickness were significantly increased ,while prazosin could signif‐icantly inhibit the plaque formation and intima hyperplasia ;compared with the normal diet group ,the expression level of MMP‐1 protein in the high fat diet group and prazosin group was significantly increased ,while the TIMP‐1 protein expression level was de‐creased ,moreover the MMP‐1 protein expression level in the prazosin group was lower than that in the high fat diet group ,while the TIMP‐1 protein expression level was higher than that in the high fat diet group ,the differences were statistically significant (P<0 .05) .Conclusion Prazosin can decrease the level of TC and LDL‐C ,increase the HDL‐C level and has certain anti‐atherosclerotic effect ,its mechanism may be related with the decrease of the MMP‐1 level and the increase of the TIMP‐1 level in plaque .
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Objective To detect the concentrations of plasma matrix metalloproteinases-9(MMP-9)and tis- sue inhibitor of matrix metalloproteinase-1(TIMP-1)of patients perioperatively with breast carcinoma,to investigate their relationships with tumor progress,and to could evaluate patients'condition by dynamic detection of plasma MMP-9 and TIMP-1.Methods The perioperative plasma concentrations of MMP-9 and TIMP-1 in patients were detected by ELISA technique in 42 cases breast carcinoma.Results The preoperative concentrations of plasma MMP-9 and TIMP-1 were significantly higher in breast carcinoma than those in normal control(P
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Objective To investigate the expression of the cytosolic phospholipase A2(c-PLA2),interleukin-1 beta(IL-1?),tissue inhibitor of matrix metalloproteinase-1(TMP-1) in rat brain after injury.Methods The model of traumatic brain injury originally described by Feeney was employed.The mRNA was analyzed by RT-PCR.Results The mRNA of cytosolic phospholipase A2 was increased at 2 hour and its peak was at 7 day.At 14 day,the level of cytosolic phosphalipase A2 mRNA was still in high level as compared to the control group.Likely,the enhancement expression of interleukin-1? was seen at the 1 hour and the peak time was from 5 to 8 hour.At 72 hour,it decreased to normal level.The expression of inhibitor of matrix metalloproteinase-1 was increased at the 2 hour,and the highest expression level was seen during 48 to72 hour.It came down to normal level at 14 day after injury.Conclusion The augment of the expression of the cytosolic phospholipase A2,interleukin-1? and tissue inhibitor of matrix metalloproteinase-1 following traumatic brain injury suggested that they participated in the pathogenesis of the traumatic brain injury,and may played roles in this pathophysiological process.
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PURPOSE: Bronchial asthma is an inflammatory respiratory disease characterized by the activation of inflammatory cells and its infiltration. It has been recently reported that MMP- 9 dose an importance role in the movement of inflammatory cells through basal membrane, that the function may be suppressed by TIMP-1. We studied to know the change of MMP-9 and TIMP-1 in sputum before and after corticosteroid (CS) therapy, and the relation with MMP-9/TIMP-1 ratio and improvement of FEV1. METHODS: Seventeen acute moderate to severe asthmatics were selected as was a control group of 17 healthy children. MMP-9 and TIMP-1 in sputum were measured on the 0 day, 7 days and 3 months later and observed as to the flow of time. FEV1 was measured before the CS therapy and 3 months later, and the change of FEV1 & FEV1 at 3 months were compared with the relation of MMP-9/TIMP-1 ratio. RESULTS: Sputum MMP-9 was lowered more at 7 days and 3 months compared with 0 day (P< 0.05). Sputum TIMP-1 was significantly high on 7 days (P< 0.05) and then had a tendency to decrease until 3 months (P< 0.05). MMP-9/TIMP-1 ratio decreased according to the flow of time (P< 0.05). MMP-9/TIMP-1 ratio at 3 months closely correlated with the change of FEV1 (r=0.65, P< 0.05). CONCLUSION: These data suggest that the overproduction of MMP-9 after asthma exacerbation correlates with airway inflammation and TIMP-1 production might contribute to airway fibrosis. MMP-9/TIMP-1 ratio at 3 months correlates with improvement of pulmonary function after CS therapy.
Subject(s)
Child , Humans , Asthma , Fibrosis , Gelatinases , Inflammation , Matrix Metalloproteinase 1 , Matrix Metalloproteinase 9 , Membranes , Prednisolone , Sputum , Tissue Inhibitor of Metalloproteinase-1ABSTRACT
BACKGROUND: Excessive extracellular matrix (ECM) deposition by airway inflammation is presumed to play an important role in the pathogenesis of worsening airflow obstruction (Ed- acceptable three-word noun) seen during acute exacerbations of chronic bronchitis. Although many proteases can cleave ECM molecules, matrix metalloproteinases (MMPs) and their inhibitors are likely to be the physiologically relevant mediators of ECM degradation. OBJECTIVES: The purpose of this study was to demonstrate that antibiotic treatment can change airway MMPs and TIMP-1 concentrations/levels by controlling airway inflammation in acute exacerbation of chronic bronchitis. METHOD: We studied 40 patients, all of whom had an acute exacerbation of chronic bronchitis. The patients were treated with two different antibiotics, moxifloxacin and clarithromycin, in a double-blind manner for 7 days. Sputum samples were induced and collected before and after antibiotic therapy. We measured the sputum concentration of MMP-1,-9, TIMP-1, IL-8 and secretory leukocyte proteinase inhibitor (SLPI) in sputum supernatants by ELISA method. RESULTS: There was no difference after antibiotic treatment in the sputum concentrations of MMP-1,-9, TIMP-1, IL-8 and SLPI between the patients treated with moxifloxacin and those treated with clarithromycin. But the sputum concentrations of TIMP-1, and SLPI, and the TIMP-1/MMP-1 ratio were significantly reduced by the antibiotic therapy. There were significant positive correlations between sputum TIMP-1 levels and IL-8 levels (p<0.01, r=0.751), and between the sputum TIMP-1/MMP-1 ratio and IL-8 levels (p<0.01, r=0.752). The sputum SLPI levels were significantly elevated by antibiotic treatment and were negatively correlated with sputum TIMP-1 levels (p<0.01, r=-0.496) and TIMP-1/MMP-1 levels (p<0.01, r=-0.456). CONCLUSION: The study shows that the worsening of airway inflammation in acute exacerbation of chronic bronchitis is associated with an imbalance between the concentrations/levels of TIMP-1 and MMPs. Antibiotic treatment can prevent progression of airway narrowing in acute exacerbation of chronic bronchitis by modulation of the protease and anti-protease imbalance.
Subject(s)
Humans , Anti-Bacterial Agents , Bronchitis, Chronic , Clarithromycin , Enzyme-Linked Immunosorbent Assay , Extracellular Matrix , Inflammation , Interleukin-8 , Leukocytes , Matrix Metalloproteinase 1 , Matrix Metalloproteinases , Peptide Hydrolases , Sputum , Tissue Inhibitor of Metalloproteinase-1ABSTRACT
Objective To observe the renal expression of cyclooxygenase-2 (COX-2) in rats with type 2 diabetes, and explore the effect of selective COX-2 inhibitor Mobic on the expression of renal COX-2, matrix metalloproteinase-9(MMP-9), tissue inhibitor of matrix metalloproteinase-1(TIMP-1), TXB 2 and 6-Ket-PGF1?, as well as renal structure and function. Methods All rats were divided into control group, diabetes mellitus group and treatment group. Type 2 diabetic rats were treated with Mobic and vehicle respectively. Immunohistochemistry was used to detect the expression of COX-2,MMP-9 and TIMP-1 in renal tissues. The urinary TXB 2 and 6-Ket-PGF1? concentration was determined by radioimmunoassay at 6th week. Results There were an increasing expression of COX-2, TIMP-1 and decreasing MMP-9 expression in the renal tissue of type 2 diabetic rats. Mobic could increase MMP-9 expression and depress TIMP-1 expression througth inhibiting the expression of COX-2 in the renal tissues of type 2 diabetic rats. Conclusion COX-2 was involved in the pathogenesis of type 2 diabetic nephropathy. Selective COX-2 inhibitor Mobic might exert its renoprotective effects through inhibiting COX-2 activity, decreasing prostagladins systhesis, and modulating MMP-9 and TIMP-1 expression.
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The turnover of collagen is controlled by the balance between collagen synthesis and degradation. The production of collagenase (matrix rnetalloproteinase 1) and its inhibitor, tissue inhibitor of matrix metalloproteinase-1(TIMP-1) are one of the substances which rgulate this balance. The periodontal ligament fibrobIast plays an important role in collagen metabolism during orthodontic treatlment and is believed to be an origin of the osteoblast in the alveolar bone. The collagenase secreted by the periodontal ligament fibroblast and the osteoblast initiates the bone resorption by removing the osteoid layer in the alveloar bone. The interleukin 1beta is secreted by the macrophage during orthodontic treatment. The present study was undertaken to assess the effect of mechanical stress and interleukin lbeta on the expression of collagenase and TIMP 1 in the periodontal ligament fibroblasts using reverse transcription polymerase chain reaction and immunohistochemical staining. The periodontal ligament frbroblasts were stretched by placing the Petriperm(R) dish on the top of spheroidal convex watch glass(5% surface increase) and treated with interleukin 1beta (1.0 ng/ml), or treated with both of them. Treatrnent with mechanical stress and/or interleukin 1beta resulted in increased collagenase mRNA expression. The mechanical stress treated group (1.61, 1.62, 1.37 fold increase), the interieukin-1beta treated group, (1.68, 1.60, 3.78 fold increase), the mechanical stress and interleukin-lbeta treated group (1.89, 1.72, 5.48 fold increase) induced increases in collagenase mRNA compared with the control group after 2, 4, 8 hours respectively. But, TIMP-1 mRNA expressions at experimental groups were decreased after 2, 4 hours and increased after 8 hours. The mechanical stress treated group (0.16, 0.49 fold decrease and 3.77 fold incease), the interleukin-lbeta treated group (0.15, 0.44 fold decrease and 4.46 fold increase), the mechanical stress and interleukin-lbeta treated group (0.15, 0.69 fold decrease and 4.81 fold increase) induced changes in TlMP-1, mRNA compated with the control group after 2, 4, 8 hours, respectively. immunohistochemical stain showed that increased collagenase and TIMP-1 staining of the mechanical stress treated group, the interleukin-1beta treated group and the mechanical stress and interleukin-1beta treated group compared with that of the control group after 8hours. These findings suggest that mechanical stress and interleukin 1beta regulate expressions of collagenase and TIMP-1.