Extracellular matrix metalloproteinase inducer in interstitial pneumonias

Extracellular matrix metalloproteinase inducer (EMMPRIN), a glycosylated transmembrane protein that induces matrix metalloproteinases (MMPs), is minimally expressed in the normal adult lung. We previously reported that it is up-regulated in murine bleomycin-induced lung injury. In this study, we determined the expression of EMMPRIN and its association with MMP-2, MMP-7, and MMP-9 in interstitial pneumonias (IPs). We performed immunohistochemistry for EMMPRIN and MMPs on lung tissue from 22 subjects with various IPs. We did bronchoalveolar lavage (BAL) on 9 of these subjects and 13 others with IPs to measure the soluble EMMPRIN in BAL fluid. For comparison, immunohistochemistry or BAL was done on 14 subjects without IPs. The staining intensity for each protein was scored from 0 to 3 in various epithelial cell types. Soluble EMMPRIN in BAL fluid was measured by an enzyme-linked immunosorbent assay. Extracellular matrix metalloproteinase inducer was prominent in abnormal epithelial cells. It was more prominent in hyperplastic type II cells, compared with epithelium in alveolar bronchiolization. It was also elevated in BAL fluid from the subjects with IPs. Matrix metalloproteinases were expressed in cells expressing EMMPRIN, although the profile of MMPs varied among the different abnormal epithelial cell types with MMP-2 and MMP-7 in hyperplastic type II cells and MMP-7 and MMP-9 in cells showing squamous metaplasia and cells comprising bronchiolization. These results suggest a role of EMMPRIN in reepithelialization in IPs.     

EMMPRIN基因沉默对巨噬/泡沫细胞中MMP-9表达及单核细胞迁移能力的影响

目的:观察细胞外基质金属蛋白酶诱导因子(EMMPRIN)基因沉默对巨噬/泡沫细胞中基质金属蛋白酶9(MMP-9)表达以及单核细胞迁移能力的影响。方法:根据RNA干扰原理,设计合成EMMPRIN-siR-NA。通过荧光定量PCR和Western blotting观察巨噬、泡沫细胞中EMMPRIN基因和蛋白被抑制情况。采用West-ern blotting观察特异性抑制EMMPRIN表达对巨噬、泡沫细胞中MMP-9蛋白表达的影响,通过迁移实验观察特异性抑制EMMPRIN表达对单核细胞迁移能力的影响。结果:采用EMMPRIN-siRNA转染巨噬、泡沫细胞,抑制细胞内EMMPRIN的基因和蛋白表达(P0.01)后使巨噬、泡沫细胞中MMP-9的蛋白表达减少了50%和40%。此外特异性抑制EMMPRIN表达使单核细胞在趋化因子MCP-1、VEGF趋化诱导下迁移能力明显减弱(P0.05)。结论:EMMPRIN基因沉默使巨噬、泡沫细胞中MMP-9的蛋白表达明显减少、活性明显减弱同时使单核细胞的趋化迁移能力降低。由此可见EMMPRIN在MMP的表达、活化及单核细胞迁移中扮演重要角色,可能成为防治动脉粥样硬化新的治疗靶点。     

EMMPRIN modulates epithelial barrier function through a MMP-mediated occludin cleavage: implications in dry eye disease

Dry eye is a common disease that develops as a result of alteration of tear fluid, leading to osmotic stress and a perturbed epithelial barrier. Matrix metalloproteinase-9 (MMP-9) may be important in dry eye disease, as its genetic knockout conferred resistance to the epithelial disruption. We show that extracellular matrix metalloproteinase inducer (EMMPRIN; also termed CD147), an inducer of MMP expression, participates in the pathogenesis of dry eye through MMP-mediated cleavage of occludin, an important component of tight junctions. EMMPRIN expression was increased on the ocular surface of dry eye patients and correlated with those of MMP-9. High osmolarity in cell culture, mimicking dry eye conditions, increased both EMMPRIN and MMP-9 and resulted in the disruption of epithelial junctions through the cleavage of occludin. Exogenously added recombinant EMMPRIN had similar effects that were abrogated in the presence of the MMP inhibitor marimastat. Membrane occludin immunostaining was markedly increased in the apical corneal epithelium of both EMMPRIN and MMP-9 knock-out mice. Furthermore, an inverse correlation between EMMPRIN and occludin membrane staining was consistently observed both in vitro and in vivo as a function of corneal epithelial cells differentiation. These data suggest a possible role of EMMPRIN in regulating the amount of occludin at the cell surface in homeostasis beyond pathological situations such as dry eye disease, and EMMPRIN may be essential for the formation and maintenance of organized epithelial structure.     

Soluble EMMPRIN (extra-cellular matrix metalloproteinase inducer) stimulates the migration of HEp-2 human laryngeal carcinoma cells, accompanied by increased MMP-2 production in fibroblasts

The basement membrane functions as a barrier against the invasion of cancer cells. It is therefore important to investigate the mechanism of basement membrane degradation by matrix metalloproteinases (MMPs). Previously, cancer cells were long considered to be the major source of MMPs; however, current evidence indicates that most MMPs in cancer tissue are produced by stromal rather than cancer cells. A glycoprotein highly expressed on the cancer-cell membrane, EMMPRIN (extra-cellular matrix metalloproteinase inducer), exhibits the potential role of the MMP inductor in stromal cells. Depending on the cell type, EMMPRIN can stimulate the production of MMP-1, MMP-2, and MMP-3. We here report that soluble full-length EMMPRIN is liberated from HEp-2 human laryngeal epidermoid carcinoma cells, probably via microvesicle shedding. Soluble EMMPRIN stimulates human fibroblasts to produce MMP-2, after which the augmented migration of HEp-2 cells occurs, as observed in an invasion chamber assay with separately cultured fibroblasts. An anti-EMMPRIN function-blocking antibody reduced MMP-2 activity in the conditioned medium and inhibited the migration of HEp-2; obviously, EMMPRIN activity contributes to cancer-cell migration. We postulate that soluble EMMPRIN probably triggers the promotion of cancer invasion in vivo.     

Progesterone receptor modulator CDB-2914 induces extracellular matrix metalloproteinase inducer in cultured human uterine leiomyoma cells

Effects of progesterone receptor modulator CDB-2914 on the expression of the extracellular matrix (ECM) components were examined in cultured human uterine leiomyoma and myometrial cells. ECM metalloproteinase inducer (EMMPRIN), matrix metalloproteinases (MMPs), tissue inhibitors of MMP (TIMPs) and collagen levels were assessed by Western blot analysis, MMP activity assay and real-time RT-PCR. RNA interference (RNAi) of EMMPRIN was performed using small interfering mRNA. In cultured leiomyoma cells, CDB-2914 treatment at concentrations greater than or equal to 10(-8) M significantly increased EMMPRIN, MMP-1 and MMP-8 protein contents and MMP-1, MMP-2, MMP-3 and MMP-9 mRNA levels, and activity of MMP-1, MMP-2, MMP-3 and MMP-9 in the medium. TIMP-1 and TIMP-2 were significantly decreased at mRNA and protein levels by CDB-2914 treatment at concentrations > or =10(-7) M in these cells. CDB-2914 treatment decreased types I and III collagen protein contents. However, CDB-2914 treatment did not affect the ECM component expression in cultured myometrial cells. RNAi of EMMPRIN abrogated CDB-2914-mediated both induction of MMPs and reduction of TIMPs and collagens in cultured leiomyoma cells. These results suggest that CDB-2914 modulates the expression of EMMPRIN, MMPs, TIMPs and collagens in cultured leiomyoma cells without comparable effects on myometrial cells.     

PPARs配体对巨噬细胞、泡沫细胞细胞外基质金属蛋白酶诱导因子表达的影响

目的：观察PPAR α、γ配体对巨噬细胞、泡沫细胞细胞外基质金属蛋白酶诱导因子(EMMPRIN)表达的影响。方法：体外诱导THP-1单核细胞转化为巨噬细胞、泡沫细胞，分别加入PPAR α配体氯贝特（clofibrate）、PPARγ配体吡格列酮(pioglitazone)共同培养，应用Real-time RT-PCR和Western blotting测定巨噬细胞、泡沫细胞中EMMPRIN基因和蛋白表达，ELISA测定细胞培养上清液MMP-9浓度，Zymgraphy法测定MMP-9活性。结果：氯贝特和吡格列酮均能显著抑制巨噬细胞和泡沫细胞EMMPRIN的表达，此抑制作用与PPAR α、γ配体抑制MMP-9分泌及活性的趋势一致。结论：PPAR α、γ配体均可抑制巨噬细胞、泡沫细胞EMMPRIN的表达，下调EMMPRIN可能是PPARs配体抑制粥样斑块局部MMPs产生的机制之一。     

高糖和茶多酚对人脐静脉内皮细胞基质金属蛋白酶2及其诱导因子表达的影响

目的 探讨高糖对内皮细胞基质金属蛋白酶2(MMP-2)及其诱导因子(EMMPRIN)表达的影响,以及茶多酚对高糖作用的干预情况.方法 培养人脐静脉内皮细胞,分为正常对照组、高糖组、茶多酚对照组和茶多酚干预组.培养24 h后,用免疫细胞化学、RT-PCR和Western blot法测定细胞内MMP-2及EMMPRIN的变化.结果 高糖下调内皮细胞MMP-2及EMMPRIN表达,其变化随时间延长更为明显;而茶多酚干预组MMP-2活性明显上调(P<0.05);茶多酚干预组EMMPRINmRNA及蛋白表达均较高糖组上调(P<0.05),茶多酚干预可拮抗高糖对内皮细胞的影响.结论 高糖影响内皮细胞的细胞外基质降解,茶多酚可以抑制这种作用.     

Ventilator-induced lung injury upregulates and activates gelatinases and EMMPRIN: attenuation by the synthetic matrix metalloproteinase inhibitor, Prinomastat (AG3340).

Mechanical ventilation has become an indispensable therapeutic modality for patients with respiratory failure. However, a serious potential complication of MV is the newly recognized ventilator-induced acute lung injury. There is strong evidence suggesting that matrix metalloproteinases (MMPs) play an important role in the development of acute lung injury. Another factor to be considered is extracellular matrix metalloproteinase inducer (EMMPRIN). EMMPRIN is responsible for inducing fibroblasts to produce/secrete MMPs. In this report we sought to determine: (1) the role played by MMPs and EMMPRIN in the development of ventilator-induced lung injury (VILI) in an in vivo rat model of high volume ventilation; and (2) whether the synthetic MMP inhibitor Prinomastat (AG3340) could prevent this type of lung injury. We have demonstrated that high volume ventilation caused acute lung injury. This was accompanied by an upregulation of gelatinase A, gelatinase B, MT1-MMP, and EMMPRIN mRNA demonstrated by in situ hybridization. Pretreatment with the MMP inhibitor Prinomastat attenuated the lung injury caused by high volume ventilation. Our results suggest that MMPs play an important role in the development of VILI in rat lungs and that the MMP-inhibitor Prinomastat is effective in attenuating this type of lung injury.     

Tumorigenic potential of extracellular matrix metalloproteinase inducer

Extracellular matrix metalloproteinase inducer (EMMPRIN), a glycoprotein present on the cancer cell plasma membrane, enhances fibroblast synthesis of matrix metalloproteinases (MMPs). The demonstration that peritumoral fibroblasts synthesize most of the MMPs in human tumors rather than the cancer cells themselves has ignited interest in the role of EMMPRIN in tumor dissemination. In this report we have demonstrated a role for EMMPRIN in cancer progression. Human MDA-MB-436 breast cancer cells, which are tumorigenic but slow growing in vivo, were transfected with EMMPRIN cDNA and injected orthotopically into mammary tissue of female NCr nu/nu mice. Green fluorescent protein was used to visualize metastases. In three experiments, breast cancer cell clones transfected with EMMPRIN cDNA were considerably more tumorigenic and invasive than plasmid-transfected cancer cells. Increased gelatinase A and gelatinase B expression (demonstrated by in situ hybridization and gelatin substrate zymography) was demonstrated in EMMPRIN-enhanced tumors. In contrast to de novo breast cancers in humans, human tumors transplanted into mice elicited minimal stromal or inflammatory cell reactions. Based on these experimental studies and our previous demonstration that EMMPRIN is prominently displayed in human cancer tissue, we propose that EMMPRIN plays an important role in cancer progression by increasing synthesis of MMPs.     

成纤维细胞与结肠癌细胞相互作用促进细胞外基质金属蛋白酶诱导因子的表达

目的研究成纤维细胞与结肠癌细胞相互作用对二者表达细胞外基质金属蛋白酶诱导因子（EMMPRIN）的影响,初步探讨肿瘤-基质相互作用在结肠癌侵袭转移中的作用。方法结肠癌SW480细胞与HELF成纤维细胞以RPMI1640培养液分别共培养0、12、24、48h,通过RT-PCR和免疫细胞化学方法检测SW480和HELF细胞中EMMPRIN的表达。结果共培养组SW480细胞EMMPRINmRNA和蛋白的表达均明显升高,HELF细胞本来不表达EMMPRIN,与SW480细胞共培养12、24、48h后检测到EMMPRIN表达,且随时间延长而表达增加。结论成纤维细胞与结肠癌细胞相互作用上调SW480细胞EMMPRIN的表达,并诱导HELF细胞表达EMMPRIN,有可能在结肠癌侵袭转移中发挥重要作用。     

The role of matrix metalloproteinase 7 in innate immunity

Matrix metalloproteinase 7 (MMP-7), or matrilysin, is a secreted protease expressed by glandular and mucosal epithelial cells, keratinocytes, fibroblasts and macrophages. As with other MMPs it can act on the extracellular matrix and thereby regulate cell migration and tissue repair. In addition, MMP-7 has an important role in the maintenance of innate immunity in organs such as the lungs and intestines where it proteolytically activates anti-bacterial peptides such as pro-defensins. MMP-7 is also important for mediating proteolytic release of TNF from macrophages. Consistent with its role in innate immunity, MMP-7 is induced by microbial products and also, unexpectedly, by hypoxia.     

聚肌胞苷酸刺激的上皮细胞对成纤维细胞活化的影响及EMMPRIN的作用

 目的：探讨聚肌胞苷酸［poly(I:C)］作用上皮细胞后对气道成纤维细胞增殖和转分化的影响及细胞外基质金属蛋白酶诱导因子(EMMPRIN)的作用。方法：以poly(I:C)作用于人肺泡上皮细胞,将细胞上清刺激人气道成纤维细胞或种植在胶原凝胶中的成纤维细胞,观察后者增殖、α-平滑肌肌动蛋白(α-SMA)和EMMPRIN表达及凝胶收缩;以EMMPRIN刺激成纤维细胞,检测细胞增殖、α-SMA表达及MMP-2、-9活性水平;应用p38 MAPK和ERK1/2抑制剂,观察对α-SMA表达及EMMPRIN分泌的影响。结果：Poly(I:C)作用的上皮细胞上清诱导成纤维细胞增殖、α-SMA和EMMPRIN表达及凝胶收缩;EMMPRIN剂量依赖性增强细胞增殖、α-SMA表达及MMP-2、-9活性;poly(I:C)作用的上皮细胞上清激活成纤维细胞p38 MAPK和ERK1/2信号通路,两者特异性阻断剂减弱成纤维细胞α-SMA和EMMPRIN表达。结论：Poly(I:C)作用上皮细胞后诱导成纤维细胞增殖、α-SMA表达和凝胶收缩,p38 MAPK和ERK1/2信号通路介导了上述过程,EMMPRIN是其中重要介质。     

Expression of gelatinase B and the extracellular matrix metalloproteinase inducer EMMPRIN in benign and malignant pigment cell lesions of the skin.

By the degradative effect on basement membrane collagen type IV, matrix metalloproteinases (MMPs) or gelatinases are important in the early invasion of malignant tumors. These enzymes may be released by the tumor cells themselves or may be derived from nearby fibroblasts that have been stimulated by the extracellular MMP inducer EMMPRIN. We studied the distribution of 92-kd gelatinase B (MMP-9) and of EMMPRIN in 33 benign and 41 malignant, paraffin-embedded pigment cell lesions using immunohistochemistry and monoclonal antibodies. In benign pigment cell lesions, EMMPRIN but not gelatinase B was expressed in cellular blue nevi whereas all other benign lesions, including common blue nevi, were negative. In malignant melanomas (MMs), both gelatinase B and EMMPRIN were variably expressed in the pure and invasive radial growth phase but not in the vertical growth phase. All lentigo maligna cases and all metastatic lesions were negative. Of MMs with thickness < 1.6 mm, 63% expressed gelatinase B and 70% expressed EMMPRIN, whereas in MMs with > 1.6 mm thickness, only 10% expressed gelatinase B and only 25% expressed EMMPRIN. We conclude that early invasion of MM is associated with de novo expression of gelatinase B and EMMPRIN by neoplastic melanocytes. Expression of EMMPRIN and MMP-9 may be partly responsible for the stromal changes observed in thin MM. Their absence in the vertical growth phase and in metastatic lesions suggests that other factors are involved in tissue degradation during later stages of tumor progression in MM. The lack of both gelatinase B and EMMPRIN in lentigo maligna may contribute to the indolent behavior of this type of pigment cell lesion.     

Matrix metalloproteinase production by COOH-terminal heparin-binding fibronectin fragment in rheumatoid synovial cells

Fibronectin with IIICS region is present in rheumatoid synovium, and fibronectin fragments are increased in rheumatoid joints. We investigated the ability of COOH-terminal heparin-binding fibronectin fragment (COOH-HBFN-f) containing IIICS to induce matrix metalloproteinase (MMP) production and the role of mitogen-activated protein kinase (MAPK) pathway and CS-1 sequence that can bind alpha4beta1 integrin in MMP induction by COOH-HBFN-f in rheumatoid synovial fibroblasts (RSF). When RSF in monolayer culture were incubated with COOH-HBFN-f, COOH-HBFN-f stimulated the production of MMP-1, MMP-3, and MMP-13 by RSF in association with activation of extracellular signal-regulated kinase, p38 MAPK, and c-Jun NH(2)-terminal kinase. Immunoprecipitation of cell lysates demonstrated the presence of alpha4 integrin in cultured RSF. Similar to COOH-HBFN-f, treatment with CS-1 synthetic peptide derived from IIICS resulted in increased MMP production and activation of the kinases, although the MMP levels were low. Preincubation of RSF with anti-alpha4 integrin antibody resulted in partial suppression of the COOH-HBFN-f-stimulated MMP production. Inhibition studies using protein kinase inhibitors (PD98059 and SB203580) showed that those MAPK pathways contributed to MMP up-regulation by COOH-HBFN-f and CS-1. Thus, the present results have clearly shown that COOH-HBFN-f and CS-1 stimulate MMP production in association with activation of MAPK pathways in RSF. Integrin alpha4beta1 may be partially involved in the MMP induction by COOH-HBFN-f.     

High extracellular matrix metalloproteinase inducer/CD147 expression is strongly and independently associated with poor prognosis in colorectal cancer

As in most solid tumors, colorectal cancer prognosis strongly depends on the extent of local invasion and lymph node and distant metastases. Extracellular matrix metalloproteinase inducer (EMMPRIN) is a transmembrane glycoprotein that activates matrix metalloproteinases, a group of enzymes that play an important role in tumor invasion and metastasis formation. This study investigates the EMMPRIN expression in a large cohort of patients with colorectal cancer. Immunohistochemical analysis of tissue microarrays from 285 patients shows that increased EMMPRIN protein expression does not correlate with clinicopathologic parameters and is an independent prognostic factor of poor survival, with mean survival times of 103 months in EMMPRIN negative/low versus 57 months in EMMPRIN intermediate/high patients (P < .001). This pronounced association of increased EMMPRIN levels and--on average--a 45% reduction in overall survival could help improve the risk stratification in patients with colorectal cancer; moreover, the lack of correlations with classical measures of cancer invasion/spreading may suggest the relevance of alternative EMMPRIN pathways beyond matrix metalloproteinase activation.     

EMMPRIN-mediated MMP regulation in tumor and endothelial cells

Tumor invasion and metastasis are multistep processes which require extracellular matrix remodeling by proteolytic enzymes such as matrix metalloproteinases (MMPs). The production of these enzymes is stimulated by many soluble or cell-bound factors. Among these factors, extracellular matrix metalloproteinase inducer (EMMPRIN) is known to increase in vitro stromal cell production of MMP-1, MMP-2 and MMP-3. In this study, we demonstrated that EMMPRIN-transfected MDA-MB-436 tumor cells displayed a more invasive capacity than vector-transfected cells in a modified Boyden chamber invasion assay. Using gelatin zymography and protein analyses, we showed that EMMPRIN-transfected cancer cells produced significantly more latent and active MMP-2 and MMP-3 than vector-transfected cancer cells. We found that EMMPRIN did not regulate MMP-1, MMP-9, membrane type-1 MMP (MT1-MMP) expression and had also no effect on the production of the specific tissue inhibitors of MMPs (TIMPs), TIMP-1 and TIMP-2. We also demonstrated that tumor-derived EMMPRIN stimulated MMP-1, -2, and -3 without modification of MMP-9, MT1-MMP, TIMP-1 and TIMP-2 production in human umbilical vein endothelial cells (HUVEC). These data provide support for the role of EMMPRIN in tumor invasion, metastasis, and neoangiogenesis by stimulating extracellular matrix remodeling around tumor cell clusters, stroma, and blood vessels. This revised version was published online in July 2006 with corrections to the Cover Date.     

Selective progesterone receptor modulator asoprisnil down-regulates collagen synthesis in cultured human uterine leiomyoma cells through up-regulating extracellular matrix metalloproteinase inducer

BACKGROUND: A recent clinical trial demonstrated that selective progesterone receptor modulator asoprisnil is effective in reducing uterine leiomyoma volume. We investigated the effects of asoprisnil in vitro on the expression of the extracellular matrix (ECM)-remodeling enzymes and collagens in cultured leiomyoma and matching normal myometrial cells. METHODS: The expression of extracellular matrix metalloproteinase inducer (EMMPRIN), matrix metalloproteinases (MMPs), tissue inhibitors of MMP (TIMPs) and collagens were assessed by western blot analysis. RESULTS: Untreated cultured leiomyoma cells had significantly lower EMMPRIN (P < 0.05), MMP-1 (P < 0.05) and membrane type 1-MMP (MT1-MMP) (P < 0.01) protein contents, but significantly higher TIMP-1 (P < 0.05), TIMP-2 (P < 0.01), type I (P < 0.05) and type III (P < 0.01) collagen protein contents compared with untreated cultured myometrial cells. Treatment with asoprisnil at concentrations > or =10(-7) M for 48 h significantly (P < 0.05) increased EMMPRIN, MMP-1 and MT1-MMP protein contents, and decreased TIMP-1 (P < 0.05), TIMP-2 (P < 0.01), type I (P < 0.01) and type III (P < 0.05 at 10(-7) M; P < 0.01 at 10(-6) M) collagen protein contents in cultured leiomyoma cells compared with control cultures. However, asoprisnil treatment did not affect the protein contents of ECM-remodeling enzymes and collagens in cultured myometrial cells. CONCLUSIONS: These results suggest that asoprisnil may reduce collagen deposit in the ECM of cultured leiomyoma cells through decreasing collagen synthesis and enhancing the expression of EMMPRIN, MMPs and TIMPs without comparable effects on cultured myometrial cells.     

GSK-3-specific inhibitor-supplemented hESC medium prevents the epithelial-mesenchymal transition process and the up-regulation of matrix metalloproteinases in hESCs cultured in feeder-free conditions

Feeder-free culture induces spontaneous differentiation of humanembryonic stem cells (hESCs), identified as an epithelial tomesenchymal transition (EMT). The maintenance of pluripotencyof hESCs in feeder-free cultures through the activation of theWNT pathway using a glycogen synthase kinase (GSK)-3-specificinhibitor (BIO) was reported. The aim of this study was to determinethe effect of BIO on the EMT process. In contrast with thosegrown in feeder-free conditions with control medium, hESC coloniescultured with BIO-supplemented hESC medium did not show anyfibroblast-like cells at the periphery. Transmission electronmicroscopy, relative quantitative real-time RT–PCR andimmunostaining analyses showed the presence of epithelial featuresand a diminution of mesenchymal features in the BIO-treatedhESCs such as a strong E-cadherin expression, the down-regulationof Vimentin, Snail and Slug expressions and a cytoplasmic β-cateninexpression. An up-regulation of matrix metalloproteinases (MMP)MMP-2, MMP-9, MT-1MMP (membrane-type 1 MMP) and EMMPRIN (extracellularMMP inducer) expression was also found associated with the EMToccurring in feeder-free hESCs cultures using mouse embryonicfibroblasts conditioned medium (MEF CM). The presence of BIOclearly down-regulated the expression of these MMPs. This studyshowed that BIO, a GSK-3-specific inhibitor, prevents the EMTprocess which is associated with the feeder-free hESC culture.Nevertheless, BIO was not sufficient to expand hESCs in a long-termculture system.     

The effect of the expression of angiotensin II on extracellular matrix metalloproteinase inducer (EMMPRIN) in macrophages is mediated via the AT1/COX-2/PGE2 pathway

Aim  

To explore the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) in THP-1 macrophages induced by angiotensin II (Ang II) and the mechanism of EMMPRIN expression.     

Immunohistochemical expression of matrix metalloproteinases in the rabbit corneal epithelium upon UVA and UVB irradiation

Matrix metalloproteinases (MMPs) are proteolytic enzymes involved in tissue remodeling and wound healing. These enzymes degrade and also synthesize components of the extracellular matrix. Overexpression of MMPs results in excessive extracellular matrix degradation and tissue destruction. In the cornea, destructive processes may lead to scarring and loss of vision. In this study MMPs (types 1, 2, 7, 8, 9 and 14) were examined immunohistochemically in the normal rabbit corneal epithelium and in epithelium irradiated in vivo with similar doses of UVB or UVA radiation (UVB rays 312 nm, UVA rays 365 nm, daily dose 1.01 J/cm² for four days). Results show that MMPs studied revealed low expression in the normal corneal epithelium, whereas after repeated UVB irradiation the expression of MMPs was significantly increased in the corneal epithelium, in ascending order: MMP-2, MMP-9, MMP-1, and MMP-7 with MMP-8. In contrast, compared to normal corneas, repeated UVA radiation did not significantly change the expression of MMPs in the irradiated corneal epithelium. MMP-14 was expressed at very low levels in all studied corneas, whereas no significant changes were detected upon UV exposure. In conclusion, UV radiation of shorter wavelength (UVB) induced an increase in expression of all MMPs except MMP-14. It is suggested that overexpression of MMPs in the corneal epithelium contributes to the damaging effect of UVB radiation to the cornea.