LOW DOSE PIRFENIDONE SUPPRESSES TRANSFORMING GROWTH FACTOR BETA-1 AND TISSUE INHIBITOR OF METALLOPROTEINASE-1, AND PROTECTS RATS FROM LUNG FIBROSIS INDUCED BY BLEOMYCIN

Objective To investigate the optimal dosage of pirfenidone for the treatment of pulmonary fibrosis induced by bleomycin in Wistar rats, and the alteration of expressions of transforming growth factor beta-1 (TGF-β_ 1), tissue inhibitor of metalloproteinase-1 (TIMP-1), and matrix metalloproteinase-13 (MMP-13) in lung tissue. Methods Male Wistar rats were endotracheally instilled with bleomycin or normal saline. Pirfenidone (25-[KG*8]800 mg·kg -1·d -1), dexamethasone (3 mg/kg), or 1% carboxymethylcellulose sodium were given daily by feed 2 days before instillation of bleomycin. Groups T7 and T14 were fed pirfenidone 50 mg·kg -1·d -1 at 7 days or 14 days after bleomycin instillation. Lungs were harvested at 28 days after bleomycin instillation. Patholological changes in lung tissues were evaluated with HE staining. Lung collagen was stained by sirius red and measured by content of hydroxyproline. Expression of proteins of TGF-β_ 1, TIMP-1, and MMP-13 were detected by Western blotting. Results At doses of 25, 50, and 100 mg·kg -1·d -1, pirfenidone had significant anti-fibrotic effects for bleomycin-induced rat pulmonary fibrosis, and these effects were most significantly attenuated at the dosage of 50 mg·kg -1·d -1 (HE: P<0.01, P<0.01, and P=0.064; sirius red: P<0.05, P<0.01, and P<0.05; hydroxyproline: P=0.595, P<0.01, and P=0.976). Pirfenidone at a dosage of[KG*3]50 mg·kg -1·d -1 inhibited protein expression of TGF-β_ 1 and TIMP-1 in lung tissue in the early phase (0.79 and 0.75 times of control group), but had no effect on expression of MMP-13. Conclusion Low dose pirfenidone, especially at dosage of 50 mg·kg -1·d -1, has significant anti-fibrotic effects on bleomycin-induced rat pulmonary fibrosis. Pirfenidone partially inhibits the enhancement of the expression of TGF-β_ 1 and TIMP-1 in lung tissue.

Expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 in hepatic stellate cells during rat hepatic fibrosis and its intervention by IL-10

AIM: To investigate the expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 in hepatic fibrosis and the antifibrogenic role of exogenous interleukin-10 (IL-10).METHODS: Hepatic fibrosis was induced by CCl4administration and 60 male Sprague-Dawley rats were randomly divided into normal control group (group N, 8rats), CCl4-induced group (group C, 28 rats) and IL-10-treated group (group I, 24 rats). At the beginning of the 7th and 11th wk, rats in each group were routinely perfused with pronase E and type Ⅳ collagenase through portal vein catheter and the suspension was centrifuged by 11%Nycodenz density gradient to isolate hepatic stellate cells (HSCs). RT-PCR was used to analyze mRNA of MMP-2 and TIMP-1 from freshly isolated cells. Densitometric data were standardized with β-actin signals. Immunocytochemistry was performed to detect MMP-2 and TIMP-1 expression in HSC cultured for 72 h.RESULTS: Compared to group N in the 7th wk, MMP-2and TIMP-1 mRNA increased in group C (P= 0.001/0.001)and group I (P = 0.001/0.009). The level of MMP-2 and TIMP-1 mRNA in group I was significantly lower than that in group C (P= 0.001/0.001). In the 11th wk, MMP-2 mRNAin group I was still lower than that in group C (P = 0.005),but both dropped compared with that in the 7th week (P = 0.001/0.004). TIMP-1 mRNA in group I was still lower than that in group C (P= 0.001), and increased in group C (P = 0.001) while decreased in group I (P = 0.042)compared with that in the 7th wk. Same results were found by immunocytochemistry.CONCLUSION: Expression of MMP-2 and TIMP-1 is increased in hepatic fibrosis. IL-10 exhibits an antifibrogenic effect by suppressing MMP-2 and TIMP-1 expression.

Expression of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 in ulcerative colitis

AIM: To examine the expression of metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the colonic mucosa of patients with ulcer- ative colitis (UC). METHODS: Reverse transcription-polymerase chain re- action (RT-PCR) and immunohistochemistry were used to study the expression of MMP-1 and TIMP-1 at both mRNA and protein levels in patients with UC and con- trols. The relationship between MMP-1 mRNA, TIMP-1 mRNA, MMP-1 mRNA/TIMP-1 mRNA ratio and the sever- ity of clinical symptoms of the patients with UC were also analyzed. RESULTS: The expression of MMP-1 mRNA and TIMP-1 mRNA in the ulcerated and inflamed colonic mucosa was signifi cantly higher than that in the non-inflamed colonic mucosa (P < 0.001), but there was no statistically signif i- cant difference in the non-inflamed colonic mucosa of UC patients and normal controls (P > 0.05). The mRNA ex- pression of MMP-1 and TIMP-1 in ulcerated colonic mu- cosa of UC patients was increased by 80-fold and 2.2-fold, respectively when compared with the normal controls. In the inflamed colonic mucosa, the increase was 30-fold and 1.6-fold, respectively. Immunohistochemical analy- sis showed that among the ulcerated, inflamed, and non-inflamed colonic mucosae of UC patients and the normal controls, the positive rate of MMP-1 expression was 87%, 87%, 40% and 35% respectively, and the positive rate of TIMP-1 expression was 89%, 89%, 80% and 75%, respectively. Furthermore, the expression of MMP-1 mRNA, TIMP-1 mRNA and the MMP-1 mRNA/ TIMP-1 mRNA ratio were correlated with the severity of clinical symptoms (P <0.05).CONCLUSION: Excessive expression of MMP-1 in the diseased colonic mucosa causes excessive hydrolysis of the extracellular matrix (ECM) and ulceration in UC pa-tients. MMP-1 mRNA, TIMP-1 mRNA and MMP-1 mRNA/ TIMP-1 mRNA ratio can be used as biomarkers to judge the severity of clinical symptoms in patients with UC. Exogenous TIMP-1 or MMP-1 inhibitor therapy is a novel treatment for patients with UC.

Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 expression in early focal cerebral infarction following urokinase thrombolysis in rats

Activity of matrix metalloproteinase-9 increases following cerebral ischemia/reperfusion,and is associated with cerebral microvascular permeability,blood-brain barrier destruction,inflammatory cell infiltration and brain edema.Matrix metalloproteinase-9 also likely participates in thrombolysis.A rat model of middle cerebral artery infarction was established by injecting autologous blood clots into the internal carotid artery.At 3 hours following model induction,urokinase was injected into the caudal vein.Decreased neurological severity score,reduced infarct volume,and increased expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 were observed in the cerebral cortex 24 hours after urokinase thrombolysis.These results suggest that urokinase can suppress damage in the acute-early stage of cerebral infarction.

Plasma matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 as biomarkers of ulcerative colitis activity

AIM: Overexpression of mucosal metalloproteinases (MMP)has been demonstrated recently in inflammatory boweldisease. Their activity can be counterbalanced by the tissueinhibitor of metalloproteinases (TIMP). The aim of this studywas to evaluate the effect of ulcerative colitis (UC) on MMP-1 and TTMP-1 plasma concentrations, as two possiblebiomarkers of the disease activity.METHODS: MMP-1 and TIMP-1 plasma concentrations weremeasured with an enzyme immunoassay in 16 patients withendoscopically confirmed active UC.RESULTS: Plasma concentrations of both MMP-11 (13.7±0.2ng/ml) and TIMP-L (799±140 ng/ml) were significantlyelevated in UC patients in comparison to healthy controls(11.9±0.9 ng/ml and 220±7 ng/ml respectively). There wasno correlation between TIMP-1 and MMP-1 concentrations(r=-0.02). TIMP-1 levels revealed significant positivecorrelations with scored endoscopic degree of mucosai injury,disease activity index and clinical activity index values aswell as C-reactive protein concentration. There was nocorrelation between MMP-1 and laboratory, clinical orendoscopic indices of the disease activity.CONCLUSION: These results confirm the role of both MMP-1 and TIMP-1 in the pathogenesis of ulcerative colitis.However only TIMP-1 can be useful as a biomarker of thedisease activity, demonstrating association with clinical andendoscopic pictures.

Expression of tissue inhibitor of metalloproteinase-1 in progression muscular dystrophy

Objective Tissue inhibitor of metalloproteinase-1(TIMP-1) is a multifunctional protein that has the capacity to modify cellular activities and to modulate matrix turnover. This paper revealed the contributive role of TIMP-1 in progressive muscular dystrophy (PMD). Methods We examined the expression and cellular localization of TIMP-1 protein using biopsied frozen muscle from patients with Duchenne muscular dystrophy ( DMD) , Becker muscular dystrophy (BMD) , congenital muscular dystrophy (CMD) by immunohistochemistry, double immunofluorescence and Western blot analysis. Results The results of immunohistochemistry and double immunofluorescence showed that TIMP-1 was positive only in vascular endothelial cells of normal muscles. Immunohistochemistry and Western blot analysis showed that the staining intensity was distinctly increased in some dystrophic muscles of PMD for TIMP-1. Double immunofluorescence revealed that TIMP-1 strongly expressed in the regenerating muscle fibers, macrophages and macrophage infiltrating necrotic fibers. Some activated fibroblasts in endomysium and perimysium of DMD and CMD muscles were also positive for TIMP-1. Conclusion The functional consequence of overexpression of TIMP-1 in the dystrophic muscles is unknown, but the elevated local expression of TIMP-1 in diseased muscles of PMD and their distinct distribution pattern provide evidence that TIMP-1 may participate in the pathogenesis of PMD.

Expressions of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in malignant peripheral nerve sheath tumor

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) can degrade collagen Ⅳ (the main structural ingredient of basilar membrane), and it also plays an important role in tumor vascularization, tumor cell progression, formation of metastatic focus, etc. Tissue inhibitor of metalloproteinase-1 (TIMP-1) can bind with MMP-9 to form 1∶1 compound and inhibit its activity, and can negatively regulate the tumor progression and metastasis. OBJECTIVE: To analyze the relationship of MMP-9 and TIMP-1 expressions with the pathological grade, metastasis and prognosis of malignant peripheral nerve sheath tumor (MPNST). DESIGN: An observational comparative experiment. SETTING: Heze Medical College. PARTICIPANTS: Fifty-eight surgical pathological samples, which were clearly diagnosed to be MPNST, were collected from the pathological laboratory archives in the Department of Pathology, Heze Municipal Hospital from January 1988 to December 2003. The MPNST pathological types were common tumor in 53 cases, malignant triton tumor in 2 cases, epithelial MPNST in 2 cases and MPNST with gland differentiation in 1 case. The pathological grade was grade 1 in 11 cases, grade 2 in 24 cases and grade 3 in 23 cases. Besides, the resected tumor samples of 20 patients with benign peripheral nerve tumor (10 cases of nerve sheath tumor and 10 cases of neurofibromatosis) and the normal peripheral nerves (by-products of some surgeries) of 5 patients were also collected. The samples were used with the approval of the patients. Rat-anti-human MMP-9, TIMP-1 monoclonal antibody and S-P kit were purchased from Fuzhou Maixin Biotechnology, Co.,Ltd. METHODS: The documented paraffin blocks were again prepared to sections of 5 μm. The expressions of MMP-9 and TIMP-1 in the samples were detected with mmunohistochemical S-P method. The relationships of the MPNST severity, recurrence, metastasis and survival rate with the expressions of MMP-9 and TIMP-1 were analyzed. MAIN OUTCOME MEASURES: Relationships of MMP-9 and TIMP-1 expressions with the MPNST severity and prognosis. RESULTS: ① Expressions of MMP-9 and TIMP-1 in three tissues: MMP-9 and TIMP-1 stainings were mainly observed in cytoplasm. Among the 58 MPNST patients, the MMP-9 expression was significantly higher than those in normal peripheral nerve and benign tumor (P < 0.05), while the TIMP-1 expression in MPNST was lower than those in normal peripheral nerve and benign tumor (P < 0.05). ② Relationship of MMP-9 and TIMP-1 expressions with the severity and prognosis of MPNST: The expressions of both proteins were observed in the four subtypes. The positive expression of MMP-9 in the MPNST patients of grades 2-3 was significantly higher than that in the MPNST patients of grade 1 (P < 0.05), while the expression of MMP-9 was significantly lower than that in the MPNST patients of grade 1 (P < 0.05). The metastatic rate was positively correlated with MMP-9 expression (r =1.696, P < 0.05), but negatively correlated with TIMP-1 expression (r =-2.125, P < 0.05). CONCLUSION: MMP-9 and TIMP-1 are associated with MPNST pathological grades and metastasis, and can be used as the indicators for judging the severity and prognosis of MPNST.

Long noncoding RNAs HAND2-AS1 ultrasound microbubbles suppress hepatocellular carcinoma progression by regulating the miR-873-5p/tissue inhibitor of matrix metalloproteinase-2 axis

BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is unclear.Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.AIM To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of HCC.METHODS In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,respectively.In addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior.Next,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and EMT.In vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.RESULTS We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of UTMBs.Additionally,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of TIMP2.And miR-873-5p mimic counteracted the impact of HAND2-AS1.Further,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs.We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/MMP9.In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.CONCLUSION LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression.

Effects of a plasmid expressing antisense tissue inhibitor of metalloproteinase-1 on liver fibrosis in rats

Background No efficient therapy for liver fibrosis has been available. This study was aimed to provide evidence that the introduction of a plasmid expressing antisense tissue inhibitor of metalloproteinase-1 (TIMP-1) into a rat model of immunologically induced liver fibrosis can result in the increased activity of interstitial collagenase, thus enhancing the degradation of collagen.

Effects of (-)-epigallocatechin-3-gallate on expression of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 in fibroblasts irradiated with ultraviolet A

Background It is known that ultraviolet irradiation can affect cellular function through a number of signaling pathways ( ) epigallocatechin 3 gallate (EGCG) is the major effective component in green tea and can offer protection from ultraviolet induced damage In this study, we investigated the protective mechanism of EGCG on human dermal fibroblasts damaged by ultraviolet A (UVA) in vitro Methods Transcription factor Jun protein levels were measured by Western blot Matrix metalloproteinase 1 (MMP 1) and tissue inhibitor of metalloproteinase 1 (TIMP 1) mRNA were studied by reverse transcription polymerase chain reaction (RT PCR) analysis in conjunction with computer assisted image analysis MMP 1 and TIMP 1 proteins were quantified by enzyme linked immunosorbent assay (ELISA) Results EGCG decreased transcription activity of Jun protein after induction by UVA Both the mRNA and protein levels of MMP 1 were increased by UVA irradiation, while no significant changes were observed in TIMP 1 levels The ratio of MMP 1 to TIMP 1 showed statistically significant differences compared with the control EGCG decreased the ratio of MMP 1 to TIMP 1 by inhibiting UVA induced MMP 1 expression ( P <0 05) Conclusion EGCG can protect human fibroblasts against UVA damage by downregulating the transcription activity of Jun protein and the expression of MMP 1 The ratio of MMP 1 to TIMP 1, rather than the levels of MMP 1 or TIMP 1 alone, may play a significant role in human skin

Effect of angiotensin Ⅱ receptor blocker on glucose-induced mRNA expressions of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in rat mesangial cells

细胞外的矩阵蛋白质的减少的降级玩的背景在糖尿病的 nephropathy 的发作的一个重要角色。矩阵 metalloproteinase-9 (MMP-9 ) 是矩阵 metalloproteinase 家庭的成员，和 metalloproteinase-1 (TIMP-1 ) 的织物禁止者与这个过程被联系。血管收缩素 il (AII ) 也在糖尿病的 nephropathy 的发展起一个重要作用。试图在老鼠 mesangial cells.Methods 老鼠 mesangial 房间在 MMP-9 和 TIMP-1 的导致葡萄糖的 mRNA 表情上调查血管收缩素受体 blocker 的效果的这研究进 5 个组有教养、划分：正常葡萄糖(组 NG ) ，高葡萄糖(组 HG ) ，组 NG+AII， NG+AIl+saralasin (组 NG+AII+S， saralasin 是所有受体 blocker ) 并且 HG+saralasin (组 HG+S ) 。在房间被孵化 24 个小时以后，在上层清液的所有集中被放射性免疫测定和 MMP-9 的表示测量， TIMP-1 mRNA 是由反向的抄写聚合酶链反应(RT-PCR ) 的 assayed 所有集中是的 .Results 在组 HG 更高((56.90 慮敳吗？？

Signal transducers and activators of transcription 3 mediates up-regulation of angiotensin ll-induced tissue inhibitor of metalloproteinase-1 expression in cultured human senescent fibroblasts

Backgroud 血管收缩素Ⅱ(Ang Ⅱ) ， renin-angiotensinsystem (地岬) 的一个主要受动器并且在老化纸巾增加了，能经由 theG-protein-coupled Ang Ⅱ受体类型Ⅰ(AT1 ) 刺激 JAK/STAT 小径并且导致信号变换器的原子 translocation 和抄写(STAT ) 的使活跃之物。为了推进，在老化探索 Ang Ⅱ的角色，我们在人的 replicative 上检验了 Ang Ⅱ的效果衰老的双成纤维细胞 WI-38 房间。方法人的衰老的 WI-38 房间与 Ang Ⅱ，受体对手 PD123319， valsartan， STAT3 感觉原生质标志，或 STAT3 反感觉原生质被孵化标志。方法被使用 includingelectrophoretic 活动性移动试金(EMSA ) ，西方的污点， transfection，并且激光扫描共焦的显微镜学。有教养的人的衰老的 WI-38 房间组成地表示了 metalloproteinase-1 (TIMP-1 ) 的织物禁止者，这被发现的结果，和 Ang Ⅱ在时间依赖者和剂量依赖者礼貌导致了 TIMP-1 蛋白质表示。Ang Ⅱ在两时间也导致了 STAT-DNA 有约束力的活动 -- 并且剂量依赖者礼貌。并且超级移动试金证明导致 sis 因素(SIF ) 乐队包含了 STAT3 蛋白质。STAT3 反感觉 oligonucleotides 能禁止两项 Ang Ⅱ - inducedSTAT3-DNA 绑定活动以及 TIMP-1 表示。结论 Ang Ⅱ通过激活 STAT3 的起来调整 TIMP-1expression 能在人的衰老的房间表明小径，显示那条 Ang Ⅱ - STAT3-TIMP-1 小径可以在老化纸巾涉及硬化的机制。

Tissue inhibitor of metalloproteinase-1 counteracts glucolipotoxicity in the pancreatic β-cell line INS-1

背景 Glucolipotoxicity 可能在 metalloproteinase-1 ( TIMP-1 )的 2 diabetes.Tissue 禁止者禁止的联系肥胖的类型的发展期间在房间补偿不全阶段起一个重要作用矩阵 metalloproteinase ( MMP )活动并且调整许多房间类型的增长和 apoptosis ，包括胰腺的 -cells.In 现在的学习，我们调查了 TIMP-1 是否在胰腺的房间线 INS-1.Methods INS-1 房间抵抗 glucolipotoxicity 在正常 o

Effects of Biejia Ruangan Tablet(复方鳖甲软肝片)-Containing Serum on Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 Expression in Cultured Renal Interstitial Fibroblasts

Objective:To investigate the effects of Biejia Ruangan Tablet(复方鳖甲软肝片方,BRT)- containing serum on the expression of matrix metalloproteinase(MMP-9) and tissue inhibitor of metalloproteinase(TIMP-1) in cultured renal interstitial fibroblasts.Methods:Different BRT-containing sera were prepared by gastric gavages to rats with the high-dose(7 g/kg),mid-dose(3.5 g/kg),and low-dose(1.75 g/kg)BRT respectively.The expression of extracellular matrix in NRK-49 F cells was induced by treatment with human transforming growth factor-β1(recombined human TGF-β1),and BRT-containing serum.Western blotting and Northern blotting were used to measure type Ⅰ and Ⅲ procollagen,MMP-9,and TIMP-1.Results:The high dose BRT-containing serum could decrease the type Ⅰ and Ⅲ procollagen gene expression which boosted by TGF- β1,at the same time cut down TIMP-1 protein and gene expression which increased by TGF- β1(P<0.05).Treatment of cells with recombined human TGF- β 1 had no significant effect on MMP-9 expression and BRTcontaining serum also had no effect on MMP-9 expression.Conclusions:High dose BRT has anti-fibrosis effects in NRK-49 F cells,as indicated by its inhibition of type Ⅰ and Ⅲ procollagen and TIMP-1 expression.

Synergistic antitumor effects of in vivo production of human endostatin and tissue inhibitor of metalloproteinase-1 in mice after subcutaneous implantation of primary fibroblasts transfected by adenovirus-mediated gene delivery

metalloproteinase (TIMP ) 的背景织物禁止者 -1 是多功能的蛋白质。学习的目的是检验使用 TIMP-1 正 endostatin 和细胞移植技术的调停侵入人体气管粘膜的病菌的基因交货的联合在老鼠 melanoma.Methods 对待肿瘤生长和转移的可行性连接酶的 immunosorbent 试金( ELISA )被用来在 vitro 并且在检测 TIMP-1 和 endostatin 的水平 vivo 。适用的老鼠模型和试验性的肺转移在动物实验建模的一个肿瘤被用来探索治疗学的效果在在感染显示的侵入人体气管粘膜的病菌进忍受肿瘤的老鼠和一个细胞化学的方法的主要成纤维细胞的培植以后的人的 TIMP-1 和 endostatin 的 vivo 生产被用来观察组织病理学说的变化肿瘤。一个试验性的肺转移模型被把 B16BL6 房间注入老鼠的尾巴静脉建立，感染侵入人体气管粘膜的病菌的主要成纤维细胞 24 个小时以后皮下地被植入进老鼠。在肿瘤房间注射以后的 21 天，老鼠被牺牲在在 B16BL6 cells.Results TIMP-1 象黑形式在肺的表面上可见的小瘤上检验效果， endostatin 被分泌进 Ad-TIMP-1 和 Ad-End-infected 老鼠的文化的上层清液主要成纤维细胞。我们也观察了独自感染 Ad-TIMP-1 的成纤维细胞的那培植，广告结束独自一个，或 Ad-TIMP-1 正广告结束导致了可以清楚地在这些结果建议的鼠科的黑瘤 model.Conclusion 禁止肿瘤生长和转移的可检测的血层次为 TIMP-1 或 endostatin 基因的交货的 transfection 的高能力构造进主要成纤维细胞，并且证明在在哪儿的 vivo 在一个地点生产成纤维细胞的 TIMP-1 和 endostatin

Interleukin-1 beta up-regulates tissue inhibitor of matrix metalloproteinase-1 mRNA and phosphorylation of c-jun N-terminal kinase and p38 in hepatic stellate cells

瞄准：学习在 interleukin-1beta (IL-1beta ) 之间的关系矩阵 metalloproteinase-1 (TIMMP-1 ) 的起来调整的织物禁止者 mRNA 表示和两 c-jun N 终端激酶(JNK ) 和在老鼠的 p38 的磷酸化肝的星形细胞(HSC ) 。方法：RT-PCR 被执行在老鼠 HSC 测量 TIMMP-1 mRNA 的表示。西方的污点被执行在老鼠 HSC 测量 IL-1beta-induced JNK 和 p38 活动。结果：TIMMP-1 mRNA 表示(1.191+/-0.079 ) 比在控制组(0.545+/-0.091 )(P【0.01 ) 为 24 h 是有 IL-1beta (10 ng/mL ) 的许多更高的术后疗法。IL-1beta 以一种时间依赖者方式激活 JNK 和 p38。在有为 0， 5， 15， 30， 60 和 120 min 的 IL-1beta 的刺激以后， JNK 活动分别地是 0.982+/-0.299,1.501+/-0.720， 2.133+/-0.882， 3.360+/-0.452， 2.181+/-0.789，和 1.385+/-0.368。在在 15 min (P【0.01 ) 的 JNK 活动有有效差量， 30 min (P【0.01 ) 和在 0 min 的与那相比的 60 min (P【0.01 ) 。p38 活动分别地是在 6 个次点(0， 5， 15， 30， 60 和 120 min ) 的 1.061+/-0.310,2.050+/-0.863， 2.380+/-0.573， 2.973+/-0.953， 2.421+/-0.793，和 1.755+/-0.433。在在 5 点的 p38 活动有有效差量 min ( P【0.05 )， 15 min ( P【0.01 )， 30 min ( P【0.01 )和在在 3 减少的 0 min.TIMMP-1 mRNA 表示 trended 的与那相比的 60 min ( P【0.01 )与 SP600125 的不同集中组织 pretreated ( 10 micromol/L ， 1.022+/-0.113 ；20 micromol/L， 0.869+/-0.070；40 micromol/L， 0.666+/-0.123 ) 。他们的减少都是重要的(P【0.05， P【0.01， P【0.01 ) 与控制组相比(没有 SP600125 处理， 1.163+/-0.107 ) 。在其它， 3 与 SB203580 的不同集中组织 pretreated (10 micromol/L， 1.507+/-0.099；20 micromol/L， 1.698+/-0.107；40 micromol/L， 1.857+/-0.054 ) ， TIMMP-1 mRNA 的表示增加了。他们的层次比在控制组的那些高(没有 SB203580 处理， 1.027+/-0.061 ) 与重要统计意义(P【0.01 ) 。结论：IL-1beta 在老鼠 HSC 由起来调整的 TIMMP-1 mRNA 表示在肝的纤维变性上有一个直接行动。JNK 和 p38 激活 mitogen 的蛋白质家族 ases (MAPK ) 涉及 IL-1beta-induced TIMMP-1 基因表示，并且在这进程起一个不同作用，显示 p38 和 JNK 小径合作地调停在老鼠 HSC 的 TIMP-1 mRNA 表示。

Imbalance of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-1 may contribute to hemorrhage in cerebellar arteriovenous malformations

In this study,we determined the expression levels of matrix metalloproteinase-2 and-9 and matrix metalloproteinase tissue inhibitor-1 and-2 in brain tissues and blood plasma of patients undergoing surgery for cerebellar arteriovenous malformations or primary epilepsy(control group).Immunohistochemistry and enzyme-linked immunosorbent assay revealed that the expression of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-1 was significantly higher in patients with cerebellar arteriovenous malformations than in patients with primary epilepsy.The ratio of matrix metalloproteinase-9 to matrix metalloproteinase tissue inhibitor-1 was significantly higher in patients with hemorrhagic cerebellar arteriovenous malformations compared with those with non-hemorrhagic malformations.Matrix metalloproteinase-2 and matrix metalloproteinase tissue inhibitor-2 levels were not significantly changed.These findings indicate that an imbalance of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-1,resulting in a relative overabundance of matrix metalloproteinase-9,might be the underlying mechanism of hemorrhage of cerebellar arteriovenous malformations.

Tissue Inhibitor of Metalloprotease-1(TIMP-1)Regulates Adipogenesis of Adipose-derived Stem Cells(ASCs)via the Wnt Signaling Pathway in an MMP-independent Manner

Tissue inhibitor of m etalloprotease-1(TIM P-1)is a tissue inhibitor o f matrix metalloproteinases(MMPs).It however exerts multiple effects on biological processes,such as cell growth,proliferation,differentiation and apoptosis,in an MMP-independent manner.This study aimed to examine the role of TIMP-1 in adipogenesis of adipose-derived stem cells(ASCs)and the underlying mechanism.We knocked down the TIMP-1 gene in ASCs through lentiviral vectors encoding TIMP-1 small interfering RNA(siRNA),and then found that the knockdown of TIMP-1 in ASCs promoted the adipogenic differentiation of stem cells and inhibited the Wnt/β-catenin signaling pathway in ASCs.We also noted that mutant TIMP-1 without the inhibitory activity on MMPs promoted the activation of Wnt/β-catenin pathway as well as the recombinant wild type TIMP-1 did,which indicated that the effect of TIMP-1 on Wnt/β-catenin pathway was MMPindependent.Our study suggested that TIMP-1 negatively regulated the adipogenesis of ASCs via the Wnt/β-catenin signaling pathway in an MMP-independent manner.

Correlation of matrix metalloproteinase－2, －9, tissue inhibitor－1 of matrix metalloproteinase and CD44 variant 6 in head and neck cancer metastasis

This study aimed to explore the molecular mechanism in tumor invasion and metastasis. The ex-pression of matrix metalloproteinase-2,-9 (MMP-2,MMP-9), tissue inhibitor-1 of matrix metalloprote inase(TIMP-1) , cell adhesion molecule 44 variant 6 (CD44v6) , HER2/neu and p53 was investigated in 154 pa-tients with head and neck squamous cell carcinoma (SCC) by ABC and ImmunoMax immunohistochemical method. Their clinical relevance and correlation were analysed. The expression of MMP-2, MMP-9, TIMP-1,CD44v6, HER2/neu and p53 was found in cancer cells in 87.01%, 85.71%, 68. 18%, 98.05%,55.19% and 50.65% cases respectively. Linear regression and correlation analysis revealed that there wasclose positive relationship ( P < 0.05) between the expression of MMP-2 and MMP-9, TIMP-1 and CD44v6,HER2/neu and MMP-9, MMP-2 and p53. Up-regulation of MMP-2 was accompanied by advanced T stage( P < 0.01 ) . There was also a trend of MMP-2 expression being related with tumor metastasis. Increased ex-pression of HER2/neu was found in patients with tumor recurrence( P < 0.05 ) . The expression of TIMP-1 washigher in laryngeal cancer than that in pharyngeal cancer, and higher in keratinizing and non-keratlnizing SCC than that in basaloid SCC ( P < 0.05 ) . These findings suggested that MMP-2 and MMP-9, HER2/neu andMMP-9, MMP-2 and p53 had a coordinate function in aggression of tumor; that MMP-2 had a more important function than MMP-9 in tumor invasion and metastasis; and that HER2/neu might serve as a biomarker forpoor prognosis in HNSCC.