血管内皮细胞生长因子激活Rac1引起肾小球内皮细胞通透性增高的机制

目的 探讨细胞内Rac1信号激活是否在血管内皮细胞生长因子（VEGF）增加肾小球内皮细胞的通透性和导致紧密连接酪氨酸磷酸化中起作用。 方法 采用原代培养的大鼠肾小球内皮细胞作为实验对象。通过体外研究,检测跨内皮细胞电阻抗观察不同浓度VEGF（5和50 μg/L）对内皮细胞通透性的影响。内皮细胞转染野生型Rac1和显性负性Rac1质粒后,采用免疫沉淀和免疫印迹等方法观察上述效应是否源自Rac1信号的激活,并观察紧密连接occludin蛋白酪氨酸磷酸化状态的改变。 结果 高浓度的VEGF（50 μg/L）刺激可引起大鼠肾小球内皮细胞单层通透性显著增高（P < 0.05）,并引起肾小球内皮细胞中GTP结合的Rac1和膜结合的Rac1显著增加（P < 0.01）,同时紧密连接蛋白occludin的酪氨酸磷酸化也增加（P < 0.05）。用Rac1显性负性突变体转染肾小球内皮细胞能显著减弱VEGF对occludin蛋白酪氨酸磷酸化和内皮细胞通透性的影响（P < 0.05）。 结论 高浓度的VEGF可导致肾小球内皮细胞通透性增高,其与紧密连接蛋白occludin的酪氨酸磷酸化相关,这一作用需要Rac1信号途径的激活。糖尿病中增高的VEGF可能通过Rac1激活-occludin磷酸化导致肾小球内皮通透性增高,这可能是糖尿病肾病的发病机制之一。     

血管生成素样蛋白3在合并糖尿病肝癌中的表达

目的了解血管生成素样蛋白3(ANGPTL3)mRNA在合并糖尿病(DM)肝细胞癌(HCC)和癌周组织的表达,探讨ANGPTL3和血糖代谢的关系。方法采用逆转录-聚合酶链反应(RT-PCR)检测方法,对45例HCC手术标本(其中合并糖尿病10例)的癌和癌周组织中ANGPTL3 mRNA表达水平进行了相对定量分析。结果合并糖尿病患者的HCC肿瘤组织中ANGPTL3 mRNA的表达强度和未合并糖尿病的肿瘤组织表达强度分别为2.01±0.54和1.25±0.35,(P<0.01)。在癌旁组织中,合并糖尿病的和未合并糖尿病的ANGPTL3 mRNA表达强度分别为1.55±0.46和0.95±0.35(P<0.05)。结论ANGPTL3在肝癌患者合并糖尿病中起重要作用。     

儿童原发性肾病综合征中血管生成素样蛋白3的表达

目的 研究血管生成素样蛋白3 (angiopoietin-like 3 protein，ANGPTL3)在儿童原发性肾病综合征(PNS)患者肾组织中表达分布及其参与蛋白尿发生的机制。方法 ANGPTL3分别与足细胞核标记抗原(WT1)、基底膜标记抗原类肝素硫酸蛋白多糖perlecan进行双标记法免疫荧光染色。应用免疫组化的方法检测ANGPTL3和perlecan在不同病理类型的69例PNS及血尿患儿，包括微小病变(MCD)31例、膜性肾病(MN)6例、局灶节段硬化性肾小球肾炎(FSGS)6例、IgA肾病16例、薄基底膜肾病(TBMN)10例以及2例正常对照肾组织中表达，并以IMS彩色图像分析系统量化为免疫组化指数。在MCD病例中将尿蛋白肌酐比值分别与肾组织中ANGPTL3和perlecan肾小球内染色强度及电镜下平均足突宽度(FWP)进行相关分析。对不同病理诊断时间(发病至肾穿刺)分组患儿肾小球ANGPTL3和perlecan的表达进行比较。结果 (1)ANGPTL3在正常肾组织呈现微弱的沉积，而在不同病理类型的肾病综合征患儿的肾组织的肾小球和肾小管存在不同程度的表达。肾小球内ANGPTL3表达量在MCD(7.49±1.96)、MN(6.27±0.98)中显著高于正常对照(0.02±0.001)、TBMN(0.02±0.001)及FSGS(3.14±0.49)(均P < 0.05)。在IgA肾病(系膜增生型)中，蛋白尿组肾小球中ANGPTL3表达量显著高于单纯血尿组(1.90±0.81比0.03±0.01， P < 0.05)。(2) 在MCD肾组织中，WT1及perlecan荧光双标记染色显示， ANGPTL3在足细胞胞浆及沿肾小球血管袢表达。(3) ANGPTL3在肾小球表达量分别与尿蛋白肌酐比值及电镜下平均足突宽度正相关(r为0.86、0.84，P均<0.05)，并与perlecan在肾小球内表达量负相关(r为-0.83，P < 0.05)。(4)不同发病年限的MCD患儿肾组织中肾小球ANGPTL3及perlecan的表达无显著性差异。结论 在不同程度的蛋白尿及不同足突融合程度的肾组织中存在ANGPTL3的表达差异。在MCD中，ANGPTL3主要在足细胞胞浆表达，肾小球中ANGPTL3的表达与蛋白尿程度及足细胞融合程度呈正相关。     

阿霉素肾病大鼠肾组织中血管生成素样蛋白3基因表达

目的动态观察阿霉素肾病大鼠在发生蛋白尿的过程中肾组织血管生成素样蛋白3（ANGPTL3）mRNA表达水平的变化，探讨ANGPTL3在大鼠肾组织中表达与蛋白尿的关系。方法通过激光微分离技术分离阿霉素肾病大鼠肾小球和肾小管，采用实时荧光定量RT-PCR方法分析阿霉素注射后7、14、21和28d肾组织中ANGPTL3 mRNA表达水平的变化。结果（1）阿霉素注射后第14天开始出现大量蛋白尿（P〈0.01），血清白蛋白明显减少（P〈0．01），胆固醇（P〈0．01）和甘油三酯（P〈0．05）明显增高，以上各项指标均在第28天达高峰。（2）通过激光微分离系统成功地分离了大鼠肾组织中的肾小球和肾小管。（3）阿霉素注射后7及14d后，大鼠肾皮质中总ANGFTL3 mRNA表达水平与同一时间点正常对照组比较无明显变化；到第21天时为正常对照组的9．03倍（P〈0．01）；第28天时为正常对照组的3．95倍（P〈0．05），与第21天时相比已呈现下降趋势。（4）阿霉素注射后不同时间点肾小球中ANGPTL3 mRNA表达水平的变化趋势与肾组织总ANGPTL 3mRNA表达水平的变化一致，第7、14天时，肾小球中ANGPTL 3mRNA表达水平与同一时间点正常对照组比较无明显变化；到第21天时为同一时间点正常对照组的2．18倍（P〈0．05）；第28天时为正常对照组的1．90倍（P〈0．05）。（5）阿霉素注射后不同时间点肾小管中ANGPTL3 mRNA表达水平无明显改变，与同一时间点的正常对照组相比均无显著性差异。结论正常大鼠和阿霉索肾病大鼠的肾组织中均有ANGPTL3 mRNA表达。肾组织可以自身合成ANGPTL3；肾病的大鼠肾组织自身合成ANGPTL3增多，且这种改变是发生在肾小球。ANGPTL3可能通过影响肾小球的功能参与肾病蛋白尿的进展过程。     

血管生成素样蛋白2在肿瘤研究中的进展

近年来,越来越多的研究认为肿瘤微环境中的非肿瘤细胞及细胞外基质对肿瘤的发生、发展和抗肿瘤治疗等有着重要作用。血管生成素样蛋白家族(angiopoietin-likeprotein,Angptl)是新发现的一类分泌性细胞外基质蛋白,包含7个蛋白质成员,分别为Angptl 1、2、3、4、5、6和7,其氨基酸序列与血管生成素蛋白(angiopoietin,Ang)相似,但不与Ang的受体含免疫球蛋白样环及上皮生长因子样域酪氨酸激酶1(tyrosine kinase with immunoglobulin-like and epidermalgrowth factor homology domains-1,Tie 1)和Tie 2结合。研究表明,Angptl 2、3、4、6在脂质代谢和糖代谢中起重要作用,Angptl 2、3、5、7参与调控造血干细胞的活性[1]。最近的研究发现,Angptl 2等家族成员在肿瘤发生、发展中起重要作用,可能作为抗癌治疗的新靶点而受到关注。本文对Angptl 2的结构特性及其在肿瘤中的生物学作用作一阐述。     

肾小球的通透性

一、序言肾小球毛细血管的特征:1.良好的水和电解质的通透性。2.自白蛋白起始对蛋白质的不透性;因此分子量低于白蛋白的废物可从肾排出,而电解质等一些体内有用的物质再由肾小管重吸收,以保持内环境的恒定。如肾小球受损,由于血流量低下而滤过量低下,且肾小球毛细血管通透性增加,一些在正常尿液中几乎不能见到的白蛋白等物质便排入尿液。尤其在肾病综合征时,尿蛋白高,血中蛋白质浓度减少;由于胶体渗透压降低等而出现浮肿。上述临床症状肾小球毛     

异丙酚预先给药对内毒素诱导大鼠肾小球血管内皮细胞通透性升高的影响

目的 探讨异丙酚预先给药对脂多糖(LPS)诱导大鼠肾小球血管内皮细胞通透性升高的影响.方法 分离、培养SD大鼠肾小球血管内皮细胞,以1×106/ml的密度接种于24孔培养板(200 μl/孔)和transwell小室(100 μl/室),采用随机数字表法,将其随机分为6组(n=10),正常对照组(C组)不作任何处理;脂肪乳对照组(I 组)加入10%脂肪乳4 μg/ml;异丙酚组(P组)加入异丙酚4μg/ml;LPS组(L组):加入LPS 10μg/ml;LPS+脂肪乳组(L+I组)加入10%脂肪乳4 μg/ml及LPS 10μg/ml;LPS+异丙酚组(L+P组)加入异丙酚4μg/ml 及LPS 10 μg/ml.于加入LPS前30 min加入脂肪乳或异丙酚,药物的浓度均为终浓度.加入LPS后6 h,收集细胞,采用逆转录-聚合酶链反应测定血管内皮细胞生长因子(VEGF)mRNA表达水平;收集上清液,采用酶联免疫吸附法测定VEGF浓度;测定血管内皮细胞通透性.结果 与C组比较,L组、L+I组和L+P组VEGF mRNA表达上调,上清液中VEGF浓度和血管内皮细胞通透性增加(P＜0.05),而I组和P组上述指标差异无统计学意义(P＞O.05).与L组比较,L+P组VEGF mRNA表达下凋,上清液中VEGF浓度和血管内皮细胞通透性降低(P＜0.05),L+I组上述指标差异无统计学意义(P＞0.05).上清液中VEGF浓度与血管内皮细胞通透性呈正相关(r=0.833,P＜0.05).结论 异丙酚预先给药可抑制LPS诱导大鼠肾小球血管内皮细胞通透性升高,其机制与下调VEGF表达有关.

Abstract：

Objective To investigate the influence of propofol pretreatment on the increased glomerular endothelial cell permeability induced by lipopolysaccharide (LPS) in rats.Methods Glomerular endothelial cells isolated from SD rats were cultured in 24-well plates(200 μl/well) and transwell filters (100 μl/filter) at 1×106/ml and assigned into 6 groups (n=10 each):control group (group C) , introlipid group (group I), propofol group (group P) , LPS group (group L), LPS+introlipid group (group L+I) and LPS+propofol group (group L +P). In group I, 10% introlipid 4 μg/ml was added. In group P, 4 μg/ml propofol was added. In group L, 10 μg/ml LPS was added. In group L+I, 10% introlipid 4 fig/ml combined with 10 μg/ml LPS was added. In group L+ P, 4 μg/ml propofol combined with LPS 10 μg/ml was added. Introlipid or propofol was added 30 min before the administration of LPS and the corresponding concentrations mentioned above were all final concentrations.After 6 h incubation with LPS, the cells were collected for measurement of vascular endothelial growth factor (VEGF) mRNA expression using RT-PCR. The supernatant was collected for determination of the VEGF concentration by ELJSA. The endothelial cell permeability was determined. Results Compared with group C, the expression of VEGF mRNA was up-regulated and the VEGF concentration and endothelial cell permeability were significantly increased in L, L+I and L + P groups (P＜0.05 ) ,but no significant change was found in the parameters mentioned above in I and P groups (P＞0.05). Compared with group L, the expression of VEGF mRNA was downregulated and the VEGF concentration and endothelial cell permeability were significantly decreased in L+P group (P＜0.05), but no significant change was found in the parameters mentioned above in group L+I(P＞0.05). A positive correlation existed between the concentration of VEGF and the permeability of endothelial cells(r= 0.833,P＜0.05).Conclusion Propofol pretreatment can decrease the increased glomerular endothelial cell permeability induced by LPS probably through down-regulation of VEGF expression.     

肾素血管紧张素系统在晚期糖基化终产物改变肾小球内皮细胞通透性中的作用

【摘要】 目的 探讨晚期糖基化终产物（AGE）对大鼠肾小球内皮细胞（rGEnC）紧密连接的影响及激活细胞内肾素血管紧张素系统（RAS）在其中的作用。 方法 采用原代培养的rGEnC,予不同浓度AGE（20、40、80 mg/L）分别作用6 h、12 h和24 h,采用跨内皮细胞电阻抗和异硫氰酸荧光素标记的牛血清白蛋白滤过率观察通透性的变化;Western印迹检测晚期糖基化终产物受体(RAGE)、紧密连接蛋白[occludin、claudin-5、连接黏附分子A（JAM-A）和闭合小环蛋白1（ZO-1）]和细胞RAS组分[血管紧张素原、肾素和血管紧张素Ⅱ（AngⅡ）1型受体（AT1）]蛋白表达量的变化;免疫荧光技术显示紧密连接的完整性;紫外光法和酶免疫分析技术测定细胞内外血管紧张素转化酶（ACE）活性及AngⅡ水平。 结果 AGE可引起内皮细胞通透性、RAGE表达量、ACE活性、AngⅡ浓度和AT1表达量的升高,occludin、claudin-5和JAM-A表达量的下降。加入抗RAGE抗体（100 mg/L）预处理后,上述AGE作用被阻断。AGE可引起上述紧密连接蛋白在细胞连接处的中断。予卡托普利（1 mmol/L）或缬沙坦（10 μmol/L）预处理可部分阻断AGE上述效应。 结论 AGE可通过上调RAGE表达,激活细胞内肾素血管紧张素系统,破坏肾小球内皮细胞紧密连接,导致其通透性的升高。     

血管生成素样蛋白3的表达及其与肝细胞癌侵袭和生长的关系研究

目的了解血管生成素样蛋白3（ANGPTL3）mRNA在肝细胞癌（HCC）和癌周组织的表达,探讨ANGPTL3和HCC侵袭和转移的关系,为分子水平干预肿瘤血管生成,预防HCC复发和转移打下基础.方法采用逆转录-聚合酶链反应（RT-PCR）检测方法,对45例HCC手术标本的癌和癌周组织中ANGPTL3mRNA表达水平进行了相对定量分析.结果肿瘤组织中ANGPTL3mRNA的表达率93.3%（42/45）,癌周组织中表达率77.8%（35/45）,两者无显著差异（P＞0.05）.但肝癌组织中ANGPTL3mRNA的表达强度明显高于癌周组织.ANGPTL3mRNA的表达和肿瘤的新生血管生成,癌栓的形成和肿瘤分级相关,而和肿瘤大小,包膜的完整性无明显相关.结论ANGPTL3在HCC的侵袭和转移中发挥重要作用,促进肿瘤血管形成及HCC的侵袭和转移关系密切.     

肝上皮样血管内皮细胞瘤

患者女,22岁.于2007年7月体格检查发现HBsAg、抗.Hbe、抗-HBc-IgM阳性,肝功能、AFP及CEA水平正常.上腹部CT检查发现肝左、右叶内病灶,考虑弥漫型肝癌,不排除肝转移癌或肝海绵状血管瘤.因实验室检查、临床表现无明显异常及患者经济原因,未进一步诊治.2008年12月患者复查AFP、肝功能及血常规正常,HBV DNA为2.039×103拷贝/ml.腹部超声及上腹部CT检查:肝内多发占位,考虑为肝转移癌.     

Angiopoietin 1 and vascular endothelial growth factor modulate human glomerular endothelial cell barrier properties

Normal glomerular filtration depends on the combined properties of the three layers of glomerular capillary wall: glomerular endothelial cells (GEnC), basement membrane, and podocytes. Podocytes produce endothelial factors, including angiopoietin 1 (ang1), and vascular endothelial growth factor (VEGF), whereas GEnC express their respective receptors Tie2 and VEGFR2 in vivo. As ang1 acts to maintain the endothelium in other vascular beds, regulating some actions of VEGF, these observations suggest a mechanism whereby podocytes may direct the unique properties of the glomerular endothelium. This interaction was investigated by studies on the barrier properties of human GEnC in vitro. GEnC were examined for expression of endothelium-specific markers by immunofluorescence and Western blotting and for typical responses to TNF-alpha by a cell-based immunoassay. Expression of angiopoietin and VEGF receptors was examined similarly. Barrier properties of GEnC monolayers cultured on porous supports were investigated by measurement of transendothelial electrical resistance (TEER) and passage of labeled albumin. Responses to a cAMP analogue and thrombin were examined before those to ang1 and VEGF. Results confirmed the endothelial origin of GEnC and their expression of Tie2 and VEGFR2. GEnC formed monolayers with a mean TEER of 30 to 40 Omega/cm(2). The cAMP analogue and thrombin increased and decreased TEER by 34.4 and 14.8 Omega/cm(2), respectively, with corresponding effects on protein passage. Ang1 increased TEER by 11.4 Omega/cm(2) and reduced protein passage by 45.2%, whereas VEGF reduced TEER by 12.5 Omega/cm(2) but had no effect on protein passage. Both ang1 and VEGF modulate GEnC barrier properties, consistent with potential in vivo roles; ang1 stabilizing the endothelium and resisting angiogenesis while VEGF induces the high permeability to water, characteristic of the glomerular endothelium.     

Steen solution protects pulmonary microvascular endothelial cells and preserves endothelial barrier after lipopolysaccharide-induced injury

ObjectivesAcute respiratory distress syndrome represents the devastating result of acute lung injury, with high mortality. Limited methods are available for rehabilitation of lungs affected by acute respiratory distress syndrome. Our laboratory has demonstrated rehabilitation of sepsis-injured lungs via normothermic ex vivo and in vivo perfusion with Steen solution (Steen). However, mechanisms responsible for the protective effects of Steen remain unclear. This study tests the hypothesis that Steen directly attenuates pulmonary endothelial barrier dysfunction and inflammation induced by lipopolysaccharide.MethodsPrimary pulmonary microvascular endothelial cells were exposed to lipopolysaccharide for 4 hours and then recovered for 8 hours in complete media (Media), Steen, or Steen followed by complete media (Steen/Media). Oxidative stress, chemokines, permeability, interendothelial junction proteins, and toll-like receptor 4-mediated pathways were assessed in pulmonary microvascular endothelial cells using standard methods.ResultsLipopolysaccharide treatment of pulmonary microvascular endothelial cells and recovery in Media significantly induced reactive oxygen species, lipid peroxidation, expression of chemokines (eg, chemokine [C-X-C motif] ligand 1 and C-C motif chemokine ligand 2) and cell adhesion molecules (P-selectin, E-selectin, and vascular cell adhesion molecule 1), permeability, neutrophil transmigration, p38 mitogen-activated protein kinase and nuclear factor kappa B signaling, and decreased expression of tight and adherens junction proteins (zonula occludens-1, zonula occludens-2, and vascular endothelial-cadherin). All of these inflammatory pathways were significantly attenuated after recovery of pulmonary microvascular endothelial cells in Steen or Steen/Media.ConclusionsSteen solution preserves pulmonary endothelial barrier function after lipopolysaccharide exposure by promoting an anti-inflammatory environment via attenuation of oxidative stress, toll-like receptor 4-mediated signaling, and conservation of interendothelial junctions. These protective mechanisms offer insight into the advancement of methods for in vivo lung perfusion with Steen for the treatment of severe acute respiratory distress syndrome.     

Growth properties of cultured human endothelial cells on differently coated artificial heart materials

The cultivation of autologous endothelial cells on the blood surface of artificial hearts might prevent their detrimental thromboembolic complications. To investigate the growth characteristics of endothelial cells on theoretically suitable biomaterials, we compared three polyurethanes (Pellethane, Biomer, Enka) and three silicone rubbers (Elastosil, 3145 RTV, Medical Adhesive). All synthetic surfaces were precoated with an extracellular matrix (group 1), fibronectin (group 2), or a glutaraldehyde-preserved cellular matrix (group 3). After the seeding of 2.5 x 10(4)/cm2 human endothelial cells into the various surfaces, primary adherence, growth kinetics, and maintenance of monolayer integrity were studied for 13 days. On the three polyurethanes all precoating procedures resulted in endothelial cell proliferation and the formation of persistent monolayers. In contrast, on silicone rubbers a persistent coverage with a confluent endothelium could be achieved only on the glutaraldehyde-preserved cellular matrix. When endothelial cell growth was quantitatively assessed on all precoating substrates, the glutaraldehyde-preserved cellular matrix proved to be far superior on each of the synthetics (p less than 0.001). These results demonstrate the theoretical feasibility of endothelialization of artificial hearts in vitro. Provided such an endothelium can withstand the mechanical forces within an artificial heart, in vitro endothelialization might contribute to a regained attractiveness of the elective long-term implantation of artificial hearts.     

3-脱氧葡糖醛酮诱导人血管内皮细胞凋亡

目的 探讨３－脱氧葡糖醛酮（３－ＤＧ）对人血管内皮细胞（ＶＥＣｓ）存活的影响及作用机制。方法 从人脐静脉分离血管内皮细胞并与不同浓度的３－ＤＧ在体外共同培养,细胞凋亡用形态学和原位末端标记（ＴＵＮＥＬ）法证实,凋亡或死亡细胞数量用ＦＴＴＣＡｎｎｅｘｉｎ－Ｖ及碘经丙碇（ＰＩ）染色后,以流式细胞仪检测。细胞内氧化水平以氧化敏感的荧光染料２,７－二氢二氯荧光素（ＤＣＦＨ）染色,用流式细胞仪测定。结果     

omega-3 fatty acids decrease endothelial adhesion of human colorectal carcinoma cells

BACKGROUND: Diets rich in omega-3 fatty acids have been shown to decrease both the initiation and promotion of colon carcinogenesis although their effect on hepatic metastasis formation is less well understood. Since adhesion of human colorectal carcinoma (HCRC) cells to hepatic endothelial cells is an important step in the metastatic cascade, the effect of membrane omega-3 fatty acid alterations on endothelial cell adhesion was studied. MATERIALS AND METHODS: CX-1 cells, a moderately differentiated HCRC cell line known to produce hepatic metastases in an athymic mouse intrasplenic injection model, were used. Cells were grown in omega-3 fatty acid-enriched medium and membrane-free fatty acid modifications confirmed with gas chromatography. Both human umbilical vein and hepatic sinusoidal endothelial cells were used in the binding assays. Adhesion assays were performed in a standard fashion using (51)Cr-labeled cells to tumor necrosis factor (TNF)-stimulated endothelial cell monolayers. Immunohistochemical analysis was performed for sialyl-Lewis(x), the receptor involved in endothelial adhesion on the surface of control and fatty acid-modified cells. RESULTS: Gas chromatographic analysis confirmed membrane fatty acid modification of CX-1 cells by growth in docosahexanoic acid (omega-3) (4.761 nmol/10(6) cells vs 0.057 nmol/10(6) cells for controls). Binding of CX-1 to both human umbilical vein and hepatic sinusoidal endothelial cells decreased from 38.4 +/- 0.44 to 11.58 +/- 0.87% (P < 0.01). Immunocytochemical analysis showed a decrease in sialyl-Lewis(x) expression with omega-3 treatment. CONCLUSIONS: These data indicate that omega-3 fatty acids may also be protective against the formation of hepatic metastases. The mechanism for this may be decreased endothelial cell adhesion which in turn may be due to decreased expression of the endothelial receptor sialyl-Lewis(x).     

Angiopoietin-like protein 3 induces podocytes actin rearrangement via integrin beta 3

Objective To explore whether Angiopoietin-like protein 3 (ANGPTL3) is involved in podocyte actin rearrangement, and to analyze whether integrin β3 signal pathway is a key in ANGPTL3 inducing actin rearrangement. Methods The cultured podocytes were divided into six groups: wild type, ADR treated, ADR+Dex, MOCK, ANGPTL3- cDNA, miRNA, and AD +miRNA group. (1) We observed actin cytoskeleton using Invitrogen reagents with confocal microscopy; (2) Actin cytoskeleton after blocking β3 on podocytes was; (3) The expression of total FAK and p-FAK was through Western blotting. Results (1) The wild type podocyte's cytoskeleton is arranged orderly. After ADR treatment, podocyte's actin are rearranged and weaken (P﹤0.05). There was no significant difference in actin arrangement between knock-down and MOCK group. In ANGPTL3-cDNA group the podocyte actin was also significantly rearranged; on the contrary, in miRNA+ADR group, the actin rearrangement never obviously happened (P﹤0.05). (2) Over-expression of ANGPTL3 podocytes blocked integrin β3 did not happen actin rearrangement. (3) The expression of p-FAK significantly increased in over-expression ANGPTL3 podocytes. Conclusion ANGPTL3 is a key in inducing actin rearrangement. Intergrin β3 maybe a central pathway in ANGPTL3's role with podocytes.