Radixin expression in microglia after cortical stroke lesion

Stroke induces extensive tissue remodeling, resulting in the activation of several cell types in the brain as well as recruitment of blood‐borne leucocytes. Radixin is part of a cytoskeleton linker protein family with the ability to connect transmembrane proteins to the actin cytoskeleton, promoting cell functions involving a dynamic cytoskeleton such as morphological changes, cell division and migration which are common events of different cell types after stroke. In the healthy adult brain radixin is expressed in Olig2⁺ cells throughout the brain and in neural progenitor cells in the subventricular zone. In the current study, we detected a 2.5 fold increase in the number of radixin positive cells in the peri‐infarct cortex two weeks after the induction of cortical stroke by photothrombosis. Similarly, the number of Olig2⁺ cells increased in the peri‐infarct area after stroke; however, the number of radixin⁺/Olig2⁺ cells was unchanged. Neural progenitor cells maintained radixin expression on their route to the infarct. More surprising however, was the expression of radixin in activated microglia in the peri‐infarct cortex. Seventy percent of Iba1⁺ cells expressed radixin after stroke, a population which was not present in the control brain. Furthermore, activation of radixin was predominantly detected in the peri‐infarct region of oligodendrocyte progenitors and microglia. The specific location of radixin⁺ cells in the peri‐infarct region and in microglia suggests a role for radixin in microglial activation after stroke.     

IDOL,inducible degrader of low-density lipoprotein receptor,serves as a potential therapeutic target for dyslipidemia

Low-density lipoprotein cholesterol (LDL-C) is the hall marker for the atherosclerotic cardiovascular disease (ASCVD). It has been shown that over 70% of circulating LDL-C is metabolized through binding and activation of hepatic LDL receptor (LDLR). Genetic LDLR mutations cause hypercholesterolemia in the patients. Therefore, elevation of LDLR levels is beneficial for the treatment of dyslipidemia. LDLR expression is regulated by the SREBP2/PCSK9 pathways. Targeting SREBP2/PCSK9 pathways by statins and human monoclonal PCSK9 antibody has been shown to reduce the progression of ASVCD. Recent studies identified that inducible degrader of LDLR (IDOL) is a novel regulator of LDLR. IDOL is an E3-ubiquitin ligase regulated via liver X receptors (LXRs) binding to the upstream of translation start site of IDOL. IDOL modulates LDLR distribution through ubiquitination and degradation of LDLR in lysosomes. Genome-wide association studies (GWAS) have revealed that the nonsynonymous substitution rs9370867 of IDOL probably contributes to the variability of circulating LDL levels. Recently studies also demonstrated that IDOL influences PCSK9 expression in a LDLR/SREBP2-dependent manner. Based upon these novel findings, we hypothesize that IDOL and PCSK9 would have a synergistic effect on LDLR distribution. Specifically, loss of IDOL increases LDLR distribution in the hepatic cell, and subsequently reduces serum LDL-C levels in dyslipidemic patients. IDOL might be a potential therapeutic target for the treatment of ASCVD.     

The role of the membrane cytoskeleton cross-linker ezrin in medulloblastoma cells

Medulloblastoma is a highly malignant brain tumor that occurs predominantly in children. The molecular pathogenesis of medulloblastoma is under investigation. Previously, we used complementary DNA micro-array analysis to compare patterns of gene expression in medulloblastoma samples versus normal cerebellum. The cytoskeletal protein ezrin was found to be overexpressed in medulloblastoma compared with normal cerebellum, an observation that was further validated by immunohistochemistry and real-time PCR analysis. To assess the role of ezrin in medulloblastoma, we studied ezrin’s role in medulloblastoma migration, invasion, and adhesion. Western blotting and immunofluorescence showed high expression of ezrin in four medulloblastoma cell lines, and ezrin was primarily localized to filopodia. Ezrinspecific small interfering RNA suppressed the formation of filopodia and in vitro migration, invasion, and adhesion. We also used a stably transfected medulloblastoma cell line to study the effect of ezrin overexpression. We showed that high expression of ezrin promotes filopodia formation and in vitro invasion. Finally, athymic mice implanted with ezrin-overexpressing DAOY medulloblastoma cell clones in the cerebellum showed shortened survival compared with controls. These findings suggest that, in addition to other cytoskeletal proteins, ezrin plays an important role in medulloblastoma adhesion, migration, and invasion.     

Ezrin、CD44在膀胱移行细胞癌的表达与意义

目的:探讨ezrin、CD44在膀胱移行细胞癌(BTCC)中的表达与意义。方法:采用免疫组织化学检测60例膀胱移行细胞癌与14例正常膀胱组织中ezrin、CD44的蛋白表达。结果:ezrin、CD44在膀胱移行细胞癌组织中的蛋白表达明显高于正常膀胱组织(P<0.05),ezrin、CD44的蛋白表达与膀胱移行细胞癌组织的病理分级、临床分期密切相关,ezrin、CD44蛋白表达的阳性表达随着膀胱肿瘤病理分级、临床分期的增高而增高(P<0.05)。ezrin、CD44的蛋白表达在膀胱移形细胞癌中有相关性。结论:ezrin、CD44在BTCC发生、发展过程中起重要作用。Ezrin、CD44在膀胱移形细胞癌的发生、进展中可能有协同性。ezrin可作为诊断、判断预后、指导治疗、随访检测的指标。     

ERM proteins regulate growth cone responses to Sema3A

Axonal growth cones initiate and sustain directed growth in response to cues in their environment. A variety of events such as receptor internalization, kinase activation, and actin rearrangement can be stimulated by guidance cues and are essential for mediating targeted growth cone behavior. Surprisingly little is known about how such disparate actions are coordinated. Our data suggest that ezrin, radixin, and moesin (ERMs), a family of highly homologous, multifunctional proteins may be able to coordinate growth cone responses to the guidance cue Semaphorin 3A (Sema3A). We show that active ERMs concentrate asymmetrically in neocortical growth cones, are rapidly and transiently inactivated by Sema3A, and are required for Sema3A-mediated growth cone collapse and guidance. The FERM domain of active ERMs regulates internalization of the Sema3A receptor, Npn1, and its coreceptor, L1CAM, while the ERM C-terminal domain binds and caps F-actin. Our data support a model in which ERMs can coordinate membrane and actin dynamics in response to Sema3A.     

ezrin和VEGF在乳腺癌组织中的表达及意义

目的 研究乳腺癌组织中ezrin和VEGF蛋白表达与乳腺癌临床因素和预后的关系.方法 应用免疫组化S-P法,检测63例癌组织,20例癌旁组织,30例乳腺良性肿瘤中ezrin和VEGF的表达情况.结果 ezrin和VEGF在乳腺良性肿瘤和乳腺癌癌旁组织中均无异常表达.在乳腺癌组织中,ezrin和VEGF的异常表达率分别为55.56%(35/63)和65.08%(41/63),ezrin和VEGF在乳腺癌中的表达,与其淋巴结转移、临床分期呈正相关,而与无病生存时间呈负相关(P<0.001).ezrin和VEGF在乳腺癌中的表达,与年龄、肿块大小以及月经情况无相关性(P>0.05).结论 检测ezrin和VEGF在乳腺癌中的表达,有助于判断乳腺癌的转移潜能和预后,ezrin可作为乳腺癌淋巴结转移以及判断乳腺癌预后的新指标.     

利用组织芯片技术研究埃兹蛋白的表达与肝细胞癌转移的关系

目的:研究埃兹蛋白(ezrin)在正常肝、肝细胞癌(HCC)及其转移灶中的表达情况,并探讨其表达与肝细胞癌侵袭转移的关系。方法:用组织芯片技术及免疫组化染色法检测30例正常肝、50例肝细胞癌及28例转移灶中埃兹蛋白的表达。结果:在正常肝、肝细胞癌及转移灶中,埃兹蛋白的强阳性表达率分别为0％、28％、57．1％,各组织中埃兹蛋白的表达差异均有统计学意义(P<0．05)。结论:埃兹蛋白的高表达与肝细胞癌的侵袭转移关系密切,可能是影响肝细胞癌患者预后及癌细胞转移的一个重要因素。