Activins and activin antagonists in hepatocellular carcinoma

In many parts of the world hepatocellular carcinoma (HCC)is among the leading causes of cancer-related mortality but the underlying molecular pathology is still insufficiently understood.There is increasing evidence that activins,which are members of the transforming growth factorβ(TGFβ)superfamily of growth and differentiation factors,could play important roles in liver carcinogenesis.Activins are disulphide-linked homo- or heterodimers formed from four differentβsubunits termedβA,βB,βC,andβE,respectively.Activin A, the dimer of twoβA subunits,is critically involved in the regulation of cell growth,apoptosis,and tissue architecture in the liver,while the hepatic function of other activins is largely unexplored so far.Negative regulators of activin signals include antagonists in the extracellular space like the binding proteins follistatin and FLRG,and at the cell membrane antagonistic coreceptors like Cripto or BAMBI.Additionally,in the intracellular space inhibitory Smads can modulate and control activin activity.Accumulating data suggest that deregulation of activin signals contributes to pathologic conditions such as chronic inflammation,fibrosis and development of cancer.The current article reviews the alterations in components of the activin signaling pathway that have been observed in HCC and discusses their potential significance for liver tumorigenesis.

Serum activin A as a prognostic biomarker for community acquired pneumonia

BACKGROUND It is essential to develop new biomarker with effective prognostic roles because of the unclear clinical use of the current community-acquired pneumonia(CAP)predictors.AIM To evaluate the association between serum activin A levels and prognosis in CAP patients.METHODS A total of 168 CAP individuals grouped according to the severity and prognosis of illness condition,and 48 healthy individuals as the control group were enrolled in this study.Circulating concentrations of activin A were measured using enzymelinked immunoassays.The interaction between activin A levels and etiologies of CAP was determined.Based on the severity of CAP,110 patients(65.48%)were categorized into group-I,42(25%)cases were grouped into group-II,and 16(9.52%)cases were categorized into group-III.RESULTS Serum activin A levels were higher in patients with CAP than controls,but independent of etiology.Moreover,the scores of Pneumonia Severity Index(PSI)and CURB-65 positively correlated with the increasing levels of serum activin A,and were at their highest peak in individuals in group-III(P<0.001).Combining activin A with CURB-65 or PSI was more effective in improving predictive property(P<0.01).According to Cox proportional regression analysis,after adjusting clinical parameters,we confirmed that activin A showed a powerful predictive property for hospital mortality in CAP patients(P<0.001).CONCLUSION Higher level of serum activin A was associated with poor prognosis of CAP.Activin A can be used as a more valuable biomarker of prognosis in CAP patients.

Link between mutations in ACVRL1 and PLA2G4A genes and chronic intestinal ulcers:A case report and review of literature

BACKGROUND Genetic factors of chronic intestinal ulcers are increasingly garnering attention.We present a case of chronic intestinal ulcers and bleeding associated with mu-tations of the activin A receptor type II-like 1(ACVRL1)and phospholipase A2 group IVA(PLA2G4A)genes and review the available relevant literature.CASE SUMMARY A 20-year-old man was admitted to our center with a 6-year history of recurrent abdominal pain,diarrhea,and dark stools.At the onset 6 years ago,the patient had received treatment at a local hospital for abdominal pain persisting for 7 d,under the diagnosis of diffuse peritonitis,acute gangrenous appendicitis with perforation,adhesive intestinal obstruction,and pelvic abscess.The surgical treat-ment included exploratory laparotomy,appendectomy,intestinal adhesiolysis,and pelvic abscess removal.The patient’s condition improved and he was dis-charged.However,the recurrent episodes of abdominal pain and passage of black stools started again one year after discharge.On the basis of these features and results of subsequent colonoscopy,the clinical diagnosis was established as in-flammatory bowel disease(IBD).Accordingly,aminosalicylic acid,immunotherapy,and related symptomatic treatment were administered,but the symptoms of the patient did not improve significantly.Further investigations revealed mutations in the ACVRL1 and PLA2G4A genes.ACVRL1 and PLA2G4A are involved in angiogenesis and coagulation,respectively.This suggests that the chronic intestinal ulcers and bleeding in this case may be linked to mutations in the ACVRL1 and PLA2G4A genes.Oral Kangfuxin liquid was administered to promote healing of the intestinal mucosa and effectively manage clinical symptoms.CONCLUSION Mutations in the ACVRL1 and PLA2G4A genes may be one of the causes of chronic intestinal ulcers and bleeding in IBD.Orally administered Kangfuxin liquid may have therapeutic potential.

Physiological roles of activins in the human ovary

Initially discovered in the pituitary as stimulators of follicle stimulating hormone,activins are homo-or heterodimers of inhibin subunits,which belong to the transforming growth factor-b superfamily.Subsequent studies have demonstrated that these growth factors play multifaceted roles in regulating various functions in multiple organs,including the ovary.The spatial and temporal expression of inhibin subunits(a,bA,bB,and bC),their cognate receptors,and activin-binding proteins(inhibins and follistatins)in the principal cells of growing follicles in human ovaries indicates that these activin isoforms are involved in ovarian biology.Information collected from animal studies and clinical samples suggests that these locally produced growth factors are crucial modulators of various ovarian functions,including primordial germ cell development,follicular growth and development,ovarian steroidogenesis,extracellular matrix remodeling,oocyte maturation,ovulation,and luteal function.Along with gonadotropins,intrafollicular activins exert synergistic and complementary effects on growing follicles to help them develop a mature,competent oocyte that is prepared for fertilization.Abnormal activin expression,an imbalanced activin/follistatin ratio,and the dysregulation of the activin signaling pathway have been observed in several ovarian pathologies,such as reproductive aging,polycystic ovary syndrome,and ovarian cancers.Recent advancements in our understanding of the molecular interactions and mechanisms that underlie activins and the development of related ovarian abnormalities have provided insights into disease pathogenesis and increased opportunities to achieve efficient and safe therapies.

miR-21通过调节TGF-β/activin信号通路影响人骨髓间质干细胞向成骨细胞分化的机制

目的研究miR-21调控转化生长因子(TGF)-β/activin信号通路对人骨髓间质干细胞(BMSCs)分化为成骨细胞的影响。方法将BMSCs培养后分为空白对照组(无转染)、miR-21过表达组(转染miR-21 mimics)及miR-21敲低组(转染miR-21 inhibitor)后对细胞进行转染,TGF-β/激活蛋白(activin)信号通路上miR-21的靶基因为TGF-β受体Ⅱ(TGF-βR2)、TGF-β1,RT-PCR检测miR-21、TGF-βR2、TGF-β1、骨特异性转录因子(Runx2)、成骨细胞特异基因(Osterix)mRNA;Western印迹检测TGF-βR2、TGF-β1、Runx2、Osterix蛋白;检测成骨细胞钙沉积、碱性磷酸酶(ALP)活性及骨桥蛋白(OPN)的表达。结果与空白对照组相比,miR-21过表达组中TGF-β1与TGF-βR2 mRNA及蛋白的表达均显著上升(P<0.05),而miR-21敲低组中TGF-β1与TGF-βR2 mRNA及蛋白的表达显著降低(P<0.05)。miR-21与TGF-β1、TGF-βR2基因均呈正相关(r=0.568,P<0.05;r=0.627,P<0.05)。与miR-21敲低组、空白对照组对比,miR-21过表达组可以显著提高ALP的活性、相同时间内钙沉积较明显并且其PCR扩增产物也较长。miR-21过表达组中Rumx2与Osterix mRNA及蛋白的表达较对照组显著上升(P<0.05),而miR-21敲低组中成骨细胞Rumx2与Osterix mRNA及蛋白的表达较空白对照组和miR-21过表达组显著降低(P<0.05)。miR-21与成骨细胞相关基因Rumx2、Osterix均呈正相关(r=0.627,P<0.05;r=0.516,P<0.05)。结论miR-21能够促进BMSCs分化为成骨细胞,其机制可能是通过上调TGF-β/activin信号通路中TGF-β1、TGF-βR2的表达。

Activin a拮抗剂抑制子宫内膜异位症异位病灶细胞黏附及侵袭的研究

目的:利用细胞模型研究Activin a拮抗剂对子宫内膜异位症(内异症)异位病灶间质细胞及上皮细胞黏附及侵袭的影响。方法:分离培养内异症异位病灶间质细胞及上皮细胞,分别设立Activin a单抗组(加入Activin a单抗至终浓度为0.18μg/ml)和对照组(仅加入完全培养基)。结晶紫细胞黏附实验及Transwell小室细胞侵袭实验比较Activin a单抗对异位病灶间质细胞、上皮细胞黏附和侵袭能力的影响。结果:Activin a单抗抑制异位病灶间质细胞、上皮细胞的黏附及侵袭能力。结论:Activin a拮抗剂通过抑制异位病灶细胞的黏附及侵袭可能对内异症的治疗有一定的作用。

Activin Gene in Avian Species: A Case Study

Among the avian species, understanding the roles of activin happen to be a dominant challenge in genetic evolution due to its complexity in nature. A case study of the activin gene in avian species was carried out using bioinformatics. As a sedentary bird, guinea fowl is more susceptible to local selection processes and needs a proper genetic study for conservation. The present study provides the basis for the use of activin or its target genes for the improvement of impaired wound healing, and activin antagonists for the prevention and treatment of fibrosis and the end of malignant tumors that over-express activin. The information provided will serve as a basic tool for broader genetic diversity studies to identify valuable poultry genetic resources and major genes for the development of breeding programs. This study was done by retrieving hundred (100) nucleotides and amino acid sequences of the activin gene belonging to guinea fowl and other avians from the GeneBank, aligning the sequences using BlastP determined the percent identity and phylogenetic relationship of the activin gene of guinea fowl and other avians. The shortest activin nucleotide sequence (467 bp) was observed in chicken and the longest (39896445 bp) in duck. Using the comparative sequence analysis, it was observed that the activin gene of chickens, turkeys and guinea fowl shared percent identity ranging from 91% to 95%. The percent identity reflects the degree of relatedness of species. Although closely related (90%) in ancestral line, the activin gene of guinea fowl and quail cannot be compared with guinea fowl-turkey (95%) nor guinea fowl-chicken (90%), in both biological functions and evolutionary relationship. Finally, the percent identity and similarity in function of the activin gene of guinea fowl, turkey, and chicken were in the range of 93% - 100%, indicating that the activin gene of avians possesses similar functions, well conserved and is very effective in performing functions like increasing FSH bindings, FSH-induced aromatization, improves wound healing and enhances scar formation, regulates morphogenesis of branching organs, and enhances ovarian folliculogenesis. The study, therefore, recommends farmers select and breed for activin genes in order to promote reproductive efficiency, thereby barricading species extinction.

Wnt3a和Activin A共同促进人胚胎干细胞向限定性内胚层细胞分化

【目的】研究Wnt3a和ActivinA存限定性内胚层诱导中共同作用的最佳时间窗。【方法】在无饲养层体系培养的人胚胎于细胞中，加入25ng／mLWnt3a和100ng／mLActivinA，共同作用不同时间（1～4d），收集不同作用时间点（0，1，2，3，4，5d）细胞，对原条、内中胚层前体标记Brachyury及限定性内胚层标记Sox17分别进行免疫荧光染色，统计阳性细胞总数，计算阳性细胞率。以看家基阕β-actin作为对照，采用RTPCR方法对原肠作用基因（Goosecoid（GSC）、Mixll）及三胚层发育相关基因（内胚层基因Sox17、Foxa2，内中胚层前体基因Braarchyury，中胚层基因Flk-1，外胚层基闪Pax6，胚外内胚层基因Sox7、CDX2）的表达进行检测。【结果]Wnt3a与ActivinA共同作用1～4d，均能获得限定性内胚层细胞，其中二者共同作用1d分别能获得（78．9±7．3）％Brachyury阳性细胞和（85．2±3．8）％的Sox17阳性细胞。RTPCR结果显示，在Wnt3a与ActivinA共同作用下，原肠作用基因及三胚层发育相关基因表达的时间有差异。【结论】Wnt3a和ActivinA共同作用1d，是有效促进人胚胎干细胞向限定性内胚层细胞分化的最佳作用时间窗。

林麝、马麝及梅花鹿活化素基因β_A亚基成熟肽序列的克隆和分析

活化素 (Activin)对睾丸和卵巢产生多重调节作用 ,对动物的繁育非常关键。本文参考已克隆的其它物种的活化素基因 βA 亚基成熟肽序列 ,设计一对简并引物 ,通过PCR方法从林麝 (Moschusberezovskii)、马麝 (Moschuschrysogaster)和梅花鹿 (Cervusnippon)的基因组DNA中直接扩增目的基因片段。将目的片段分别克隆到pMD1 8 T载体中 ,并进行序列测定。DNA序列测定及分析表明 ,林麝、马麝和梅花鹿的活化素基因 βA 亚基成熟肽序列长 3 45bp ,三物种核苷酸序列同源性在 98%以上 ,氨基酸序列同源性在99%以上 ,核酸限制性酶切图谱也高度相似。将它们与GenBank中已公布的其它物种的活化素序列进行比较 ,发现该片段在不同进化程度的物种间高度保守。这是首次从麝科动物中成功克隆与生殖相关的核基因 。

Activin在上皮性卵巢癌中的表达及意义

目的:检测activin在上皮性卵巢癌组织中的表达,探讨activin的表达与上皮性卵巢癌临床病理特征的关系。方法:应用免疫组织化学链霉亲和素-生物素-过氧化物霉复合物(SABC)方法,检测40例上皮性卵巢癌组织,20例良性上皮性卵巢肿瘤组织,20例正常卵巢组织中activin的表达情况。结果:上皮性卵巢癌组织中activin的阳性表达率为67.5%,高于良性上皮性卵巢肿瘤组织及正常卵巢组织的25%及10%(P<0.05),与组织学类型、临床分期无相关性(P>0.05),与组织学分级及淋巴结转移有关(P<0.05)。结论:Activin在上皮性卵巢癌组织中皆呈高表达,提示activin可能与上皮性卵巢癌的浸润、转移有关。

Expression changes of activin A in the development of hepatic fibrosis

AIM: To examine the expression of activin A, a member of the transforming growth factor (TGFbeta) superfamily, recently has been reported to be overexpressed in liver cirrhosis, in the course of carbon tetrachloride-induced rat hepatic fibrosis. METHODS: Hepatic fibrosis was induced in rats by subcutaneous injections of 40% carbon tetrachloride oily solution for a period of 1 to 7 weeks. At the end of 1, 2, 3, 4, 5, 6 and 7 weeks after carbon tetrachloride injections, the rats were killed in group (6-10 rats each time) for study. The activin A messenger RNA expression and its protein localization were assessed by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. RESULTS: The normal rat liver expressed activin A mRNA and protein, and its expression was transiently decreased and became undetectable after carbon tetrachloride injections for 2 or 3 weeks and then increased gradually. After injection of carbon tetrachloride for 6 and 7 weeks, activin A mRNA and protein expressions were significantly enhanced in rat liver. Compared with that of the normal rat liver. Activin A mRNA expression levels in rats receiving carbon tetrachloride injections for 6 and 7 weeks were 1.6 and 2.2 times that of those in normal rat liver respectively (0.456 +/- 0.094 vs 0.2860.0670, P【 0.01; 0.620 +/- 0.134 vs 0.286 +/- 0670, P【 0.01). Immunohistochemistry showed that activin A expressed in hepatocytes of normal liver, and its expression was decreased in rats receiving carbon tetrachloride for 2 or 3 weeks. Compared with normal liver, activin A expression distribution mode changed in fibrotic liver, being increased significantly in hepatocytes around fibrotic areas. CONCLUSION: Activin A expression was increased in late stage of hepatic fibrosis, and this may be involved in hepatic fibrosis formation in this period.

Activin A与子宫内膜异位症的相关性研究

目的探讨Activin A对子宫内膜细胞迁移、侵袭、增殖、黏附的影响及其机制。方法无菌收集正常分泌期子宫内膜,分离、培养内膜原代细胞,以0(对照)、8、16、32、64 ng/mL Activin A孵育内膜腺上皮细胞、间质细胞12 h。采用体外细胞划痕实验、Transwell侵袭实验探讨不同浓度Activin A对子宫内膜间质细胞、腺上皮细胞迁移、侵袭的影响;采用CCK8法检测16 ng/mLActivin A对子宫内膜间质细胞、腺上皮细胞增殖、黏附的影响;采用Real-Time PCR检测16 ng/mL Activin A作用下子宫内膜间质细胞、腺上皮细胞血管内皮生长因子A(VEGF-A)、VEGF-C mRNA表达变化。结果体外细胞划痕实验结果显示,不同浓度Activin A处理组子宫内膜细胞划痕14 h前后面积差与对照组比较,差异无统计学意义(P>0.05)。Transwell侵袭实验结果显示:8、16、32 ng/mL Activin A处理组子宫内膜间质细胞穿透细胞数量较对照组明显增多(P<0.05);16、32 ng/mL Activin A处理组腺上皮细胞穿透细胞数量较对照组明显增多(P<0.05);16 ng/mL Activin A处理组穿透细胞数量最多。经16 ng/mL ActivinA处理的子宫内膜细胞增殖、黏附能力与对照细胞比较,差异无统计学意义(P>0.05)。经16 ng/mL Activin A处理的子宫内膜间质细胞和腺上皮细胞内VEGF-A、VEGF-C mRNA的表达与对照细胞比较,差异无统计学意义(P>0.05)。结论 Activin A可显著增强子宫内膜细胞的侵袭力,而对细胞迁移、增殖和黏附能力无明显影响;Activin A并非通过调节内膜细胞VEGF-A、VEGF-C的表达而使内膜细胞的侵袭力增强。

Activin A特异性对人胚胎干细胞向限定性内胚层诱导分化的促进作用

【目的】研究Activin A对人胚胎干细胞(hESCs)向限定性内胚层(DE)诱导分化的促进作用及其信号通路分子,为hESCs向DE诱导分化体系的优化提供参考。【方法】在人饲养层体系培养的hESCs中,收集100ng/mL Activin A分别诱导0,6,12,24,48,72,96,120h的细胞,用实时荧光定量RT-PCR检测原条标记Gsc和Mixl1、中内胚层共同前体标记Brachyury、内胚层标记Foxa2和Sox17、中胚层标记Flk1、外胚层基因Pax6、多能性相关基因Oct4与Nanog表达水平的变化,用细胞免疫荧光检测Brachyury和Sox17蛋白表达水平的变化。【结果】在人饲养层(HEF)培养体系上,高浓度Activin A能更快地促进中内胚层基因的表达并提高其表达水平;Brachyury和Sox17蛋白的细胞免疫荧光检测表明,Activin A诱导12和48h就可检测二者的表达明显增加,且二者的表达水平分别在诱导48和96h时达到高峰;hESCs高效分化为限定性内胚层细胞,DE细胞分化率为(81.7±5.4)%,并且体外的内胚层分化过程遵循从原条开始、经过中内胚层共同前体阶段、再到内胚层的发育过程,与体内发育规律相似。【结论】Activin A能特异性地诱导人胚胎干细胞向限定性内胚层分化,转录调控Brachyury和Sox17蛋白的表达。

基于Activin A途径的大黄素神经保护机制的研究

目的明确大黄素对缺血缺氧性脑损伤中的神经元具有保护作用的内在机制。方法应用pc-12细胞经牛膝多肽刺激转化为神经元样细胞后,并制备神经元细胞的氧糖剥夺(OGD)模型,并在此基础上,给予大黄素干预,分别检测细胞的生存力;应用酶联免疫方法检测细胞培养基的Activin A的表达含量;应用Western blotting对caspase-3蛋白的检测。结果 pc-12细胞经牛膝多肽刺激后转化为类神经元样细胞,在OGD后的pc-12细胞呈明显的梯度变化;实验组细胞的生存力明显提高,其培养基的Activin A含量升高明显,caspase-3蛋白的表达与单纯应用氧糖剥夺组比较,表达降低(P<0.05)。结论大黄素可以提高缺血缺氧状态下神经元细胞的生存力,同时可促进激活素的表达上调,并通过下调caspase3表达来抑制神经凋亡,起到神经保护的作用。

降糖三黄片对高糖高脂饮食大鼠胰岛β细胞去分化的作用

【目的】探讨降糖三黄片对高糖高脂饮食致大鼠胰岛β细胞去分化的作用。【方法】将30只雄性SD大鼠随机分为正常组、模型组和中药组,每组10只,分别给予普通饮食、高糖高脂饮食、高糖高脂饮食并每天灌胃中成药降糖三黄片(675 mg·kg^-1·d^-1)。连续干预180 d后,检测血清空腹血糖(FBG)、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、空腹胰岛素(FINS),采用苏木素—伊红染色评估胰腺组织病理学变化,免疫组织化学法检测胰腺组织胰岛素(Insulin)、胰十二指肠同源盒因子(Pdx1)、肌腱膜纤维肉瘤癌基因同源物A蛋白(MafA)、叉头状转录因子(FOXO1)蛋白的表达。基于高通量蛋白芯片技术筛选血清差异表达细胞因子。【结果】与正常组比较,模型组大鼠FBG、TC、TG、LDL-C、HOMA-IR水平升高,FINS、HOMA-β、HDL-C水平下降,胰岛β细胞Insulin、Pdx1、MafA蛋白表达下调,FOXO1蛋白表达上调(均P<0.05)。基于高通量的蛋白芯片检测及分析,筛选出正常组和模型组有显著性差异的11种细胞因子:金属蛋白酶组织抑制物1(TIMP-1)、细胞间黏附分子1(ICAM-1)、Gas 1、肿瘤坏死因子样凋亡弱诱导因子受体(TWEAK R)、神经纤毛蛋白2(Neuropilin-2)、LIX、白细胞介素13(IL-13)、激活素A(Activin A)、血浆嗜酸性粒细胞趋化因子(Eotaxin)、半乳凝素3(Galectin-3)、Decorin(P<0.05或P<0.01)。与模型组比较,中药组大鼠FBG、TC、TG、LDL-C、HOMA-IR水平下降,FINS、HOMA-β、HDL-C水平升高,胰岛β细胞Insulin、Pdx1、MafA蛋白表达上调,FOXO1蛋白表达下调(均P<0.05)。基于高通量的蛋白芯片检测及分析,筛选出模型组和中药组有显著性差异的4个细胞因子:Galectin-3、TIMP-1、Activin A、Eotaxin(P<0.05或P<0.01)。【结论】降糖三黄片具有调控FOXO1/Pdx1通路从而延缓"糖脂毒性"作用下的β细胞去分化的作用,并与降低血清细胞因子Galectin-3、TIMP-1、Activin A、Eotaxin含量密切相关。

SMAD2介导的Activin A信号对人胚胎干细胞向限定性内胚层细胞诱导分化的促进作用

【目的】研究SMAD2在Activin A促进人胚胎干细胞向限定性内胚层诱导分化中的作用。【方法】在人胚胎干细胞中转染SMAD2基因siRNA或者过表达质粒后,收集经Activin A分别诱导0,6,12,24,48,72,96和120h的细胞各100ng/mL,采用实时定量PCR检测SMAD2与内中胚层共同前体标记Brachyury和内胚层标记Sox17的表达,进一步通过Western-blot分析Activin A诱导中SMAD2和磷酸化SMAD2(p-SMAD2)表达的变化。【结果】在Activin A诱导人胚胎干细胞向限定性内胚层细胞分化的过程中,干扰SMAD2后48h时才检测到Brachyury强表达,而单纯Activin A处理组24h就检测到强表达;Sox17的表达始终较单纯Activin A处理组明显降低,因此,干扰SMAD2直接抑制了Activin A的诱导作用。而过表达SMAD2,Brachyury和Sox17的表达水平较单纯Activin A处理组明显增加,促进了限定性内胚层的发生;并且在Activin A诱导过程中,p-SMAD2的表达水平明显提高,而SMAD2的表达没有明显改变。【结论】SMAD2作为关键因子,介导了Activin A诱导人胚胎干细胞向限定性内胚层的分化,并转录调控Brachyury和Sox17的表达;SMAD2的磷酸化,激活并介导了Activin A诱导的信号转导通路。

重组人activin A对A549细胞增殖及凋亡的影响

背景与目的:活化素(activins)是转化生长因子TGF-β超家族成员。有研究表明,活化素可以诱导多种肿瘤细胞的凋亡。本研究旨在探讨重组人activin A对人肺腺癌细胞系A549增殖及凋亡的影响。方法:体外培养A549细胞,以不同浓度activin A处理A549细胞不同时间后,用MTT法检测其生长抑制情况;流式细胞仪及Annexin V-FITC试剂盒检测activin A对A549细胞凋亡的影响;Western blot检测活化素Ⅱ型受体(ActRⅡ和ActRⅡB)的表达情况。结果:activin A能抑制A549细胞增殖,且呈剂量和时间依赖性。流式细胞仪检测结果显示,activin A能促进A549细胞凋亡。Western blot结果显示,随着activin A浓度的增加,活化素Ⅱ型受体的表达量呈浓度依赖性增加。结论:activin A能在体外抑制A549细胞的增殖并诱导其凋亡。推测是通过诱导活化素Ⅱ型受体的表达,激活其下游一系列信号转导通路,从而发挥其生物学功能。

Activin A和Lefty A对人胚胎干细胞生长的影响

目的探讨TGF-β/Activin/Nodal信号通路的相关因子Activin A和Lefty A在一定浓度范围内,对人胚胎干细胞(hESC)自我更新的影响。方法在hES3细胞株的无滋养层无血清培养体系中加入1-100ng/ml的Activin A和Lefty A。7天后,通过碱性磷酸酶染色法对hES3细胞的自我更新状态进行评估。结果 Activin A在浓度为1,3,10,30和100ng/ml时,与阴性对照(SR培养基)组相比,未分化克隆的比率从7.7%分别提高到了18.5%,46.8%,61.4%,64.4%和79.1%,差异有统计学意义(P<0.01)。Lefty A组在浓度为1,3,10,30和100ng/ml时,与阴性对照(MCM培养基)组相比,未分化克隆的比率从80.5%分别降低到了72.4%,74.6%,72.2%,69.5%和65.3%,在浓度为100ng/ml时,差异有统计学意义(P<0.05)。结论较低浓度的Activin A即能有效维持hESC的自我更新,而较高浓度的Lefty A能诱导hESC分化。该结果进一步揭示了TGF-β/Activin/Nodal信号通路及其相关因子对hESC自我更新和分化的作用特点,有待对其机制进行深入研究。

激活素Activin A对猪卵母细胞胞质成熟的影响

[目的]探讨体外成熟过程中在培养液中添加激活素Activin A对猪卵母细胞胞质成熟的影响。[方法]在TCM-199中添加不同剂量Activin A的培养猪卵母细胞40 h,以激光共聚焦显微镜观察到的着色的线粒体排布形态类型来判断卵母细胞胞质是否成熟。[结果]当Activin A剂量为100 ng/ml时,胞质中线粒体呈弥散型分布形态的卵母细胞数目极显著增加(P<0.01),同时线粒体呈圆周型排布与半周型排布的卵母细胞数目显著下降(P<0.05)。[结论]猪卵母细胞体外成熟过程中在成熟培养液中添加激活素Activin A,能促进卵母细胞胞质的成熟。

激活素A及其信号传导通路与动脉粥样硬化

1激活素的生物学作用 激活素（Activin）属于转化生长因子β（trans-forming growth factor,TGF-β）超家族成员之一。它是一种二聚体糖蛋白,是由βA、βB两个亚基通过二硫键连接而成,分别为Activin A（βA、βA）,Ac-tivin B（βB、βB）,Activin AB（βA、βB）。Activin具有广泛的组织来源,具有刺激垂体前叶腺细胞促性腺激素分泌的作用,它参与多种细胞的增殖、分化过程。同时,Activin在组织修复、