1‐(2‐Hydroxyethyl)‐2‐imidazolidinone,a heparanase and matrix metalloproteinase inhibitor,improves epidermal basement membrane structure and epidermal barrier function

Daily exposure to sunlight is known to affect the structure and function of the epidermal basement membrane (BM), as well as epidermal differentiation and epidermal barrier function. The aim of this study is to clarify whether the inhibition of BM‐degrading enzymes such as heparanase and matrix metalloproteinase 9 (MMP‐9) can improve the epidermal barrier function of facial skin, which is exposed to the sun on a daily basis. 1‐(2‐hydroxyethyl)‐2‐imidazolidinone (HEI) was synthesized as an inhibitor of both heparanase and MMP‐9. HEI inhibited not only the BM damage at the DEJ but also epidermal proliferation, differentiation, water contents and transepidermal water loss abnormalities resulting from ultraviolet B (UVB). This was determined in this study by the use of UVB‐induced human cultured skins as compared with the control without HEI. Moreover, topical application of HEI improved epidermal barrier function by increasing water content and decreasing transepidermal water loss in daily sun‐exposed facial skin as compared with non‐treated skins. These results suggest that the inhibition of both heparanase and MMP‐9 is an effective way to care for regularly sun‐exposed facial skin by protecting the BM from damage.     

Botulinum toxin blocks mast cells and prevents rosacea like inflammation

Background

Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.

Matrix metalloproteinases-2 and -9 in cervical cancer: different roles in tumor progression

The incidence of uterine cervical cancer has increased slightly in Western countries, with an increase in relatively young women. Overexpression of matrix metalloproteinases (MMPs)-2 and -9 has turned out as a prognostic factor in many cancers. We compared the expression of the proteins MMP-2 and MMP-9 in cervical primary tumors with clinical outcome and risk factors of cervical cancer. One hundred sixty-one patients with cervical cancer treated in Ume? University Hospital or Sahlgrenska University Hospital, Sweden, between 1991 and 1995 were included in the study. Paraffin-embedded tissue samples obtained prior to treatment were examined immunohistochemically by specific antibodies for MMP-2 and MMP-9. Forty-two percent of the tumors were intensively positive for MMP-2 and 31% for MMP-9. Nineteen percent of the samples were intensively positive for both proteinases and 47% negative or weak for both. Overexpression of MMP-2 seemed to predict unfavorable survival under Kaplan-Meier analysis and in the multivariate analysis. Early sexual activity and low parity seemed to correlate to overexpression of MMP-2. MMP-9 was not associated with survival or sexual behavior. Intensive MMP-9 was noted in grade 1 tumors. We conclude that MMP-2 and MMP-9 have different roles in uterine cervical cancer. MMP-2 could be associated with aggressive behavior, but MMP-9 expression diminishes in high-grade tumors.     

基质金属蛋白酶和细胞因子在强直性脊柱炎骨破坏中的作用

强直性脊柱炎(ankylosing spondylitis,AS)是以中轴关节慢性炎症为主的原因不明的全身性免疫性疾病。其特点为几乎全部累及骶髂关节,常发生椎间盘纤维环及其附近韧带钙化和骨性强直,也可累及外周关节并造成关节软骨及骨的破坏,晚期可发生脊柱及外周关节强直、畸形以致严重功能受损[1]。所以我们必须强调重视AS骨质破坏发生机制的研究,有利于寻找有效药物,减少致残。1骶髂关节炎组织学研究较系统的骶髂关节炎组织学研究表明,AS的5个阶段不同程度存在滑膜炎、骨髓黏液样变、浅表软骨破坏、肌腱端炎、关节内纤维赘、新骨形成和骨性强直等众多病理表现;其中滑膜炎和软骨下骨髓黏液样变较肌腱端炎更能合理解     

Matrix Metalloproteinase-2 and Tissue Inhibitor of Metalloproteinase-1 in the Retinal Pigment Epithelium and Interphotoreceptor Matrix: Vectorial Secretion and Regulation

Matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs) play an essential role in both normal and pathological extracellular matrix degradation, and a TIMP has been associated with at least one type of retinal degeneration. We have studied expression of MMP-2 and TIMP-1 by zymography, immunocytochemistry, and immunoblotting in the retinal pigment epithelium (RPE) from normal, aged and diseased retinas. MMPs and TIMPs were found in the rat RPE, interphotoreceptor matrix (IPM), and in media conditioned by human and rat RPE in culture. In other polarized cells, MMPs and TIMP-2 are secreted vectorially towards the basal lamina. In the RPE, however, MMP-2 and TIMP-1 were secreted preferentially from the apical surface, the surface bordering the IPM. These findings provide new evidence that MMPs and TIMPs could play a role in the turnover of IPM components.Cell homogenates and conditioned media from RPE isolated from mutant Royal College of Surgeons (RCS) rats with inherited retinal dystrophy had similar amounts of MMP-2 and TIMP-1 as those from congenic control rats. The secretion of MMP-2 and TIMP-1 from RPE cell cultures isolated from young and aged human donors varied widely. However, with increasing cell passage number, secretion of MMPs and TIMPs from human RPE increased dramatically. Also, growing human RPE on bovine corneal endothelial cell-generated extracellular matrix instead of plastic reduced the secretion of both MMPs and TIMPs. These data suggest that the integrity of Bruch's membrane may serve to regulate RPE functions in MMP and TIMP secretion and that extracellular matrices contain signals that regulate MMP and TIMP synthesis and/or secretion by the RPE.     

高血压大鼠心肌中MMP-2的蛋白表达及其RAS阻断后的变化

[目的]探讨高血压大鼠左室心肌中基质金属蛋白酶-2(MMP-2)蛋白表达的变化以及血管紧张素转化酶抑制剂(ACEI)、血管紧张素Ⅱ1型受体拮抗剂(AT1-ant)单独与联合治疗对高血压大鼠心肌中MMP-2蛋白表达的影响。[方法]40只雄性8周龄的易卒中自发性高血压大鼠(SHRSP)随机分成5组:SHRSP对照组、安慰剂组、缬沙坦组、苯那普利组及缬沙坦与苯那普利联用组。另外,取8只雄性8周龄的京都Wistar大鼠(WKY)作为对照。利用免疫组织化学的方法检测WKY以及SHRSP左室心肌中MMP-2蛋白的表达。[结果]SHRSP的收缩压(SBP)、左室质量指数(LVMI)、胶原容积分数(CVF)、血管周围胶原面积(PVCA)、左室心肌MMP-2蛋白表达较同龄的WKY显著增高。给予苯那普利、缬沙坦单独或联合治疗后SHRSP的LVMI、CVF、PVCA、左室心肌 MMP-2蛋白表达都显著降低。苯那普利、缬沙坦单独应用时的效果没有差异,而联合应用的效果更显著。[结论]SHRSP左室心肌中MMP-2蛋白表达增高,肾素血管紧张素系统(RAS)阻断后MMP-2蛋白表达显著减少;苯那普利、缬沙坦逆转高血压心室重塑的作用可能部分通过下调MMP-2蛋白表达而实现;苯那普利和缬沙坦都能降低SHRSP的血压以及逆转其左室重塑,而联合用药的作用更显著。     

基质金属蛋白酶与肺癌转移的关系

基质金属蛋白酶(matrix metalloproteinases，MMPs)是一组锌离子依赖的蛋白水解酶，在ECM降解中起着重要作用。目前研究表明，MMPs活性异常不仅能促进肿瘤血管形成，还是人类多种肿瘤侵袭和转移的必要条件。本文就与肺癌侵袭和转移有关的MMPs研究作一综述。     

Platelets as targets of snake venom metalloproteinases

For centuries snake venoms have been known to interfere with haemostasis and this is now known basically due either to toxins activating/inhibiting clotting factors, having effects on blood vessels or interfering with platelet function. In this short review, the interaction of one major group of toxins, the snake venom metalloproteinases, with platelets is considered. This is relevant for understanding the mechanism of haemorrhage induced by these toxins.     

分娩时子宫下段MMP-9及其组织抑制剂TIMP-1的变化

目的:探讨基质金属蛋白酶(MMP)及其组织抑制剂(TIMP)在分娩发动、宫颈成熟和扩张中的作用和机制.方法:采用ELISA方法测定子宫下段组织中MMP-9和TIMP-1的浓度.有宫缩剖宫产组56例,其中第一产程组44例,第二产程组12例.以无宫缩剖宫产组16例为对照组.结果:有宫缩剖宫产组子宫下段组织中MMP-9和TIMP-1的浓度分别明显高于无宫缩剖宫产组(P<0.05,P<0.05).第一产程组中随宫口开大,MMP-9和TIMP-1的浓度各组间无显著性差异.第二产程组MMP-9和TIMP-1的浓度分别明显高于第一产程组(P<0.01,P<0.05).结论:MMPs和TIMPs的动态变化是分娩发动、宫颈成熟和扩张过程中的重要中间环节.     

基质金属蛋白酶及微血管密度和子宫内膜癌的关系

基质金属蛋白酶及其抑制剂在子宫内膜癌的侵袭和转移中发挥着重要的作用。肿瘤的新生血管对肿瘤的发生、发展、转移及预后有着重要作用。微血管密度是衡量血管生成的定量指标。基质金属蛋白酶抑制剂可抑制血管的生成和MMPs对细胞外基质的降解。现将他们与子宫内膜癌的关系综述如下。