Detection of Frameshift Mutations of the Transforming Growth Factor p ReceptorⅡin Gastric Cancers with Microsatellite Instability

OBJECTIVE To study the relationship among microsatellite instability （MSI）, frameshift mutations （FM） of the transforming growth factor β receptor Ⅱ （TGF β R Ⅱ）, methylation state of the hMLH1 promoter and hMLH1 protein expression level in gastric cancers, and to explore their relationship to gastric carcinogenesis. METHODS DNA was isolated from 101 gastric specimens and 5 microsatellite loci were detected. PCR, electrophoresis on denatured polyacrylamide gels and silver staining were performed to detect the MSI. The FMs of TGFβR Ⅱ were also screened with the same method. HMLH1 methylation was analyzed by methylation specific PCR （MSP） and sequencing. HMLH1 protein expression was detected using immunohistochemistry. RESULTS The incidence of MSIs was 53.7% and 0% in the cancers and normal tissues, respectively, with the frequency of MSIs being significantly higher in the gastric cancers compared to the normal gastric tissues （P〈0.05）. The frequency of hMLH1 methylation was 41.5%（17/41） in the gastric cancers and 0%（0/60） in the normal group. Decreased hMLH1 expression was observed in 94.1%（16/17） of cases exhibiting methylation. FMs of TGFβR Ⅱ were identified in 5 （62.5%） of the 8 samples with MSIH. In contrast, FMs were not found in MSI-L or microsatellite stable （MSS） cases. CONCLUSION MSIs and FMs of TGFβR Ⅱ may play an important role in gastric carcinogenesis. HMLH1 methylation is an important modification of the DNA which results in inactivation of hMLH1 and mismatch repair defects which lead to MSls and FMs of TGFβR Ⅱ.

Transforming growth factor β receptor Ⅱ expression inexperimental cryptorchidism and apoptosisin spermatogenic cells in rats

Objective: To study the transforming growth factor β receptor Ⅱ (TGFβ-R Ⅱ) expression in experimental cryptorchidism and apoptosis in spermatogenic cells in rats. Methods: The apoptosis of spermatogenic cells was detected by means of the terminal deoxynucleotldyl transferase mediated dUTP nick end lableling method (TUNEL) and the TGFβ-R Ⅱ expression was observed with the immunohistochemistry SABC methods. Results: There was a significant increase in the TGFβ-R Ⅱ expression in unilateral undescended testes (UUTs) compared with that in contralateral descended testes (CDTs, P<0.01). However, there was a significant and time-dependent increase in the mean apoptotic index in UUTs than in CDTs. Conclusion: TGFβ-R Ⅱ may play an important role in spermatogenic cell apoptosis.

Correlation between expression of two transforming growth factor-beta 1 receptors and microvascular density in a rat model of cerebral ischemia and reperfusion injury

The effects of transforming growth factor-β1 （TGF-β1） are currently controversial. Whether TGF-β1 promotes or inhibits revascularization under different conditions remains poorly understood. Based on previous studies, the current experiment established rat models of cerebral ischemia and reperfusion injury （IRI）, and demonstrated that pathological and functional damage was also increased after IRI. The most serious damage was observed at 3 days after reperfusion, at which time microvascular density fell to its lowest level. Soon afterwards, microvascular density increased, new collateral circulation was gradually established at 4 to 7 days after reperfusion, and pathological damage and neurological deficits were improved. TGF-β1, activin receptor-like kinase 5 （ALK5） mRNA and protein expression levels increased gradually over time. In contrast, ALK1 mRNA and protein expression decreased over the same period. A significant negative correlation was detected between microvascular density and expression of the ALK5 gene transcript. There was no correlation between microvascular density and ALK1 gene transcriptional expression following cerebral IRI in a rat model. These findings suggest that ALK5, rather than ALK1, is the critical receptor in the TGF-β1 signal pathways after cerebral IRI.

Expression of transforming growth factor-β_1 and its typeⅠ receptor in different phases of post-burn hypertrophic scars

Objective: To analyze and compare the expression pattern of the transforming growth factor-β1(TGF-β1) and its type I receptor (TGF-β RI ) in nounal human skin and various phases of post-burn hypertrophic scars (HTS). Method: The immunohistochemical ABC method was employed. Results: In nounal human skin, no evident immunoreactivity of TGF-β1 and TGF-β R I was observed. In activation phase of post-burn HTS, TGF-β R I and TGF-β1 were highly expressed in most dermal fibroblasts which seemed to be the same subset. However, in remission phase, no staining was seen in der mal fibroblasts. Conclusion: The formation of all may involve the increase of TGF-β responsiveness in fibroblasts The ac cumulation at the wound site and failure of apoptosis of over-resposive fibroblasts may contribute to the formation of HTS.

Targeting Transforming Growth Factor-<i>β</i>(TGF-<i>β</i>) in Cancer and Non-Neoplastic Diseases

Transforming growth factor-β?(TGF-β) superfamily is a key player in the regulation of a wide variety of physiological processes from development to pathogenesis. Since the discovery of the prototypic member, TGF-β, almost three decades ago, there have been tremendous advances in our understanding of its complex biology. TGF-β?misregulation has been implicated in the pathogenesis of a variety of diseases, including cancer with a direct role in facilitating metastasis, fibrosis and inflammation. Consequently, TGF-β?is currently explored as a prognostic candidate biomarker of tumor invasiveness and metastasis;and it offers an attractive target for cancer therapy. Several anti-TGF-β?approaches, such as TGF-β?antibodies, antisense oligonucleotides and small molecules inhibitors of TGF-β?type 1 receptor kinase, have shown great promise in the preclinical studies. Here, we consider why the TGF-βsignaling pathway is a drug target, the potential clinical applications of TGF-β?inhibition, the issues arising with anti-TGF-β?therapy and how these might be adopted using personalized approaches with a special care for patient selection and timing of therapy so that we may bring forward all the potentials of targeting this pathway for therapeutic uses in both cancer, preferentially in combination therapy, and non-neoplastic diseases.

Reactivation of the insulin-like growth factor-Ⅱsignaling pathway in human hepatocellular carcinoma

Constitutive activation of the insulin-like growth factor (IGF)-signaling axis is frequently observed in human hepatocellular carcinoma(HCC).Especially the over- expression of the fetal growth factor IGF-Ⅱ,IGF-Ⅰ receptor(IGF-IR),and cytoplasmic downstream effectors such as insulin-receptor substrates(IRS)contribute to proliferation,anti-apoptosis,and invasive behavior. This review focuses on the relevant alterations in this signaling pathway and independent in vivo models that support the central role IGF-Ⅱsignaling during HCC development and progression.Since this pathway has become the center of interest as a target for potential anti-cancer therapy in many types of malignancies,various experimental strategies have been developed,including neutralizing antibodies and selective receptor kinase inhibitors,with respect to the specific and efficient reduction of oncogenic IGF-Ⅱ/IGF-IR-signaling.

Expression of c-erbB-2 oncogene protein, epidermal growth factor receptor, and TGF-β1 in human pancreatic ductal adenocarcinoma

Objective: To detect the relations of c-erbB-2 onco-gene protein, epidermal growth factor receptor (EG-FR) and transforming growth factor-β1 (TGF-β1)to the progression or metastasis of pancreatic carci-noma.Methods: Using streptavidinbiotin complex (SABC)method, c-erbB-2 oncongene protein, we examinedimmunohistochemically EGFR and TGF-β1 expres-sions in wax-tissue sections from 10 individuals withnormal pancreas (NP), 13 patients with chronic pan-creatitis (CP) and 36 patients with pancreatic ductaladenocarcinoma (PC).Results: The positive expression rates of c-cerbB-2oncogene protein, EGFR and TGF-β1 in the NP, CPand PC groups were 0, 0, 10%; 7.7%, 7.7%,7.7%; and 41.7%, 50.0%, 44.4%, respectively.The positive expression rates of the three specific pro-teins increased more significantly in the PC groupthan in the NP and CP groups (P【0.05). The indi-vidual expression of c-erbB-2, EGFR and TGF-β1was not related to the age and sex of the patients aswell as the site, size and histopathological grade oftumors (P】0.05), but to the clinical stage of tumors(P【0.01). The coexpression rate of the three pro-teins was 27.8 % (10/36). This coexpression in thePC group was correlated with the histopathologicalgrades and clinical stages of tumors (P【0.01).Conclusion: Detection of c-erbB-2 oncogene protein,EGFR, and TGF-β1 expressions in pancreatic tissueis helpful to judge the malignancy, progression, andmetastasis of PC.

Influence of baicalin on the expression of receptor activator of nuclear factor-κB ligand and osteoprotegerin in human periodontal ligament cells

Objective To study the effect of baicalin on the expression of receptor activator of nuclear factor-κB ligand(RANKL)and osteoprotegerin(OPG)in cultured human periodontal ligament(HPDL)cells.Methods Small interfering RNA(siRNA)eukaryotic expression vector targeted transforming growth factor βⅡ receptor(TGF-β RⅡ)was constructed and transfected into T cells.HPDL cells with T cells transfected with siRNA or not were placed in the culture medium that had been added with lipopolysaccharide(LPS)and baicalin.The obtained solution was divided into six groups according to the components(group Ⅰ:HPDL cells+LPS+T cells transfected with siRNA1+baicalin;group Ⅱ:HPDL cells+LPS+T cells transfected with siRNA1;group Ⅲ:HPDL cells+LPS+T cells+baicalin;group Ⅳ:HPDL cells+LPS+T cells;group Ⅴ:HPDL cells+baicalin;group Ⅵ:HPDL cells)and was cultured for 48 hours.RT-PCR was used to observe the effect of baicalin on the expression of OPG-RANKL in HPDL cells.Results The ratio of RANKL/OPG in group Ⅰ was lower than that in group Ⅱ(P<0.01)and higher than that in group Ⅲ(P<0.01);The ratio of RANKL/OPG in group Ⅲ was lower than that in group Ⅳ(P<0.01);the ratio of RANKL/OPG in group Ⅳ was higher than that in group Ⅵ(P<0.01);the ratio of RANKL/OPG in group Ⅴ was lower than that in group Ⅵ(P<0.05).Conclusion ① Baicalin could decrease the ratio of RANKL/OPG in HPDL cells.② The TGF-β signaling transduction plays an important role in the effect of baicalin on the RANKL/OPG ratio in HPDL cells.③ Baicalin acts not only through TGF-β to regulate RANKL/OPG in HPDL cells,but also through other pathways.

高亲和PDGFβR多肽修饰的截短型TβRⅡ的可溶性表达条件优化

目的 探讨高亲和血小板衍生生长因子受体(Platelet derived growth factor-β receptor, PDGFβR)多肽ZPDGFβR修饰的截短型转化生长因子β Ⅱ型受体(Truncated transforming growth factor-β receptor type Ⅱ,tTβRⅡ)的重组蛋白(Z-tTβRⅡ)最佳可溶性表达的条件。方法 将含有原核表达质粒pET28/Z-tTβRⅡ的阳性大肠杆菌(Rossta/pET28-Z-tTβRⅡ)置于LB培养基中培养,接着加入不同浓度的IPTG,使其终浓度为0.2、0.4、0.6、0.8 mmo/L,应用SDS-PAGE技术分析在不同温度时间下(16℃、18 h, 20℃、20 h和37℃、6 h)重组蛋白Z-tTβRⅡ的可溶性表达。结果 Z-tTβRⅡ在16℃、18 h下,0.8 mmol/L IPTG时,诱导后全菌表达约22%和诱导后上清表达约13%;Z-tTβRⅡ在20℃、20 h下,诱导后全菌0.8 mmol/L IPTG时表达约23%,诱导后上清0.2 mmol/L IPTG时表达约14%;Z-tTβRⅡ在37℃、6 h下,0.2 mmol/L IPTG时,诱导后全菌约30%和诱导后上清约20%。结论 Z-tTβRⅡ蛋白最佳表达条件为37℃、6 h、IPTG浓度为0.2 mmo/L。

Transforming growth factor-β1 involved in urotensin Ⅱ-induced phenotypic differentiation of adventitial fibroblasts from rat aorta

Background Urotensin Ⅱ （UⅡ） is a new vasoconstrictive peptide that may activate the adventitial fibroblasts.Transforming growth factor-β1 （TGF-β1） is an important factor that could induce the phenotypical transdifferentiation of adventitial fibroblasts. This study aimed to explore whether TGF-β1 is involved in UⅡ-induced phenotypic differentiation of adventitial fibroblasts from rat aorta.Methods Adventitial fibroblasts were prepared by the explant culture method. TGF-β1 protein secretion from the cells was determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expression of α-smooth nuscle actin （α-SM-actin）, the marker of phenotypic differentiation from fibroblasts to myofibroblasts, were determined using real-time quantitative RT-PCR （real-time RT-PCR） and Western blotting, respectively.Results UⅡ stimulated the secretion of TGF-β1 in cultured adventitial fibroblasts in a time-dependent manner. The secretion reached a peak at 24 hours, was higher by 69.8% （P ＜0.01）, than the control group. This effect was also concentration dependent. Maximal stimulation was reached at 10-8 mol/L of UⅡ （P ＜0.01）, which was increased by 59.9%,compared with in the control group （P ＜0.01）. The secretion of TGF-β1 induced by UⅡ was significantly blocked by SB-710411 （10-7 mol/L）, a specific antagonist of UⅡ receptor. In addition, both UⅡ （10-8 mol/L） and TGF-β1 significantly stimulated α-SM-actin mRNA and protein expression. Moreover, the α-SM-actin induced by UⅡ was inhibited by the specific neutralizing antibody （20 μg/ml） of TGF-β1, while the α-SM-actin expression stimulated by TGF-β1 （20 ng/ml）was inhibited by SB-710411 （10-7 mol/L）, the UⅡ receptor antagonist.Conclusion This study suggests that UⅡ could induce TGF-β1 secretion in adventitial fibroblasts via UT activation, and TGF-β1 might be involved in phenotypic differentiation from adventitial fibroblasts into myofibroblasts induced by UⅡ, and TGF-β1 signaling might be one of the important pathways by which UⅡ is involved in vascular fibrosis.

Controlled release of transforming growth factor-beta receptor kinase inhibitor from thermosensitive Chitosan-based hydrogel Application for prevention of capsular contracture

Background Capsular contracture has become the most common complication associated with breast implant.Transforming growth factor-beta （TGF-β） is well known for a prominent role in fibrotic diseases.Due to the critical role of TGF-β in pathogenesis of capsular formation,we utilized thermosensitive C/GP hydrogel to controlled release of TGF-β receptor kinase inhibitor （SD208） and investigated their effects on capsular contracture.Methods In vitro degradation and drug release of C/GP hydrogel were performed.Twenty-four rabbits underwent subpanniculus implantation with 30 ml smooth silicone implants and were randomly divided into four groups as fellows：Group 1 received saline solution;Group 2 received SD208;Group 3 received SD208-C/GP;Group 4 received C/GP.At 8 weeks,the samples of capsular tissues were analyzed by hematoxylin and eosin and immunohistological staining.The mRNA expression of collagen Ⅲ and TGF-β1 was detected by RT-PCR assay.Results C/GP hydrogel could be applied as an ideal drug delivery vehicle which supported the controlled release of SD208.SD208-C/GP treatment showed a significant reduction in capsule thickness with fewer vessels.The histological findings confirmed that the lower amounts of inflammatory cells and fibroblasts infiltrate in SD208-C/GP group.In contrast,typical capsules with more vessel predominance were developed in control group.We did not observe the same inhibitory effect of SD208 or C/GP treatment on capsular contracture.Moreover,SD208-C/GP therapy yielded an evident down-regulation of collagen Ⅲ and TGF-β1 mRNA expression.Conclusions This study demonstrated that controlled release of TGF-β receptor kinase inhibitor from thermosensitive C/GP hydrogel could significantly prevent capsule formation after mammary implants.

丹参酮ⅡA对高血压大鼠肥厚心肌TGF-β_1/Smads信号通路的影响

目的研究丹参酮(Tanshinone,TSN)ⅡA对压力超负荷大鼠肥厚心肌血管紧张素1型受体(angiotensin Ⅱtype 1 receptor,AT1R)、转化生长因子β1(transforming growth factor-β1,TGF-β1)与其胞内信号蛋白Smads基因表达的影响,探讨TSNⅡA抑制高血压左心室肥厚的分子机制。方法 SD大鼠行腹主动脉缩窄术建立高血压左室心肌肥厚模型,术后4周将手术大鼠随机分为模型组、丹参酮低、高剂量组[10、20mg/(kg.d)]、缬沙坦组[10mg/(kg.d)],每组8只;另有8只作为假手术组。用药8周后检测各组尾动脉压,取左心室组织检测左心室质量指数(left ventricular mass index,LVMI)、病理切片HE染色测量心肌纤维直径(myocardial fiber dimension,MFD);采用逆转录-聚合酶链式反应(reverse transcription-polymerase chain raction,RT-PCR)检测AT1R mRNA的表达水平,免疫印迹法(Western blot)分别检测TGF-β1及其胞内信号蛋白Smad-3、4、7的蛋白水平。结果 (1)丹参酮低、高剂量组血压没有变化,并显著高于假手术组和缬沙坦组(P<0.01)。(2)丹参酮低、高剂量组和缬沙坦组的LVMI、MFD均显著低于模型组(P<0.01)。(3)心肌肥厚时AT1R、TGF-β1和Smad-3的表达显著增加(P<0.01),高剂量TSNⅡA和缬沙坦都可使肥厚心肌的AT1R mRNA和TGF-β1、Smad-3蛋白水平明显下调(P<0.01),缬沙坦对TGF-β1的下调作用较丹参酮明显(P<0.05)。(4)低、高剂量的丹参酮和缬沙坦均可以使Smad-7蛋白的表达显著上调(P<0.01),丹参酮高剂量组上调作用明显超过缬沙坦组(P<0.05)。结论丹参酮ⅡA对心肌肥厚的抑制作用是非血压依赖性的,其对高血压心肌肥厚的抑制作用可能与抑制AT1R mRNA表达、阻滞TGF-β1/Smads的信号转导有关。

TGF-βRⅡ和Smad4蛋白在葡萄膜黑色素瘤中的表达

目的研究转化生长因子Ⅱ型受体(TGFβRⅡ)及其下游的抑癌基因Smad4蛋白在葡萄膜黑色素瘤中的表达。方法应用免疫组织化学SP法对24例葡萄膜黑色素瘤瘤组织中TGFβRⅡ和Smad4蛋白的表达进行检测。结果在24例葡萄膜黑色素瘤组织切片中,可见瘤细胞TGFβRⅡ阳性12例(50%),Smad4阳性11例(45.8%),两者均阳性5例,两者均阴性6例。结论葡萄膜黑色素瘤组织中存在TGFβRⅡ和/或Smad4的蛋白表达异常,可能与葡萄膜黑色素瘤的发病有关。

干扰素γ及血管紧张素Ⅱ对大鼠血管平滑肌细胞表达转化生长因子β1型受体的影响

转化生长因子β1(TGF β1)刺激细胞外基质 (ECM)生成 ,作者观察了血管紧张素Ⅱ(AngⅡ)及γ干扰素 (IFN γ)对大鼠血管平滑肌细胞 (VSMC)TGF βⅠ型受体(TβR I)表达的影响。培养大鼠VSMC ,以Western印迹法观察AngⅡ(10 -7mol/L)及IFN γ(5 0 0U/ml)作用 2 4h时对VSMCTβR I表达的影响。发现AngⅡ组TβR I表达明显高于对照组 (OD值 10 3 0 6± 9 34vs 6 2 2 4±4 39,P <0 0 1) ,IFN γ单独孵育对TβR I表达无影响 ,但可以明显抑制AngⅡ引起的TβR I表达 (OD值 81 37± 5 87)。表明AngⅡ刺激大鼠VSMCTβR I表达 ,IFN

转化生长因子β1Ⅱ型受体在大鼠慢性胰腺炎中的表达及氧化苦参碱对其的影响

目的:探讨转化生长因子β1Ⅱ型受体(TβRⅡ)在慢性胰腺炎(CP)纤维化病理进程中的作用,研究氧化苦参碱(OM)对胰腺纤维化的作用机制.方法:40只Wistar♂大鼠随机分为4组,即阴性对照组(NC组,n=10),CP模型组(CP组,n=10),OM干预组(OP组,n=10)和OM治疗组(OT组,n=10).NC组隔日给予腹腔注射生理盐水300mg/kg;其他每组均隔日腹腔注射二乙基硫代氨基甲酸盐(DDC)700mg/kg,30d停止.另外OP组于注射DDC同日开始每日腹腔注射OM100mg/kg,OT组于注射DDC1wk后开始每日腹腔注射OM100mg/kg,分别于注射DDC20d、40d后处死动物.胰腺组织行HE染色和Masson胶原染色并进行病理学评分,Western blot检测胰腺组织TβRⅡ的表达.结果:Masson染色测定结果显示,在20d、40d时CP组胶原纤维含量显著高于其余各组(20d:22.54%±4.45%vs13.16%±1.84%,19.58%±2.78%,2.45±0.24%;40d:35.14%±3.27%vs25.14%±3.67%,28.68%±2.55%,3.0%±0.32%;均P<0.05),OP组和OT组在40d时的胶原纤维面积百分比均比同组20d时增高(25.14%±3.67%vs13.16%±1.84%;28.68%±2.55%vs19.58%±2.78%;均P<0.05).West-ern blot结果显示,在20d、40d时,CP组胰腺组织TβRⅡ表达显著高于其余各组(20d:0.74±0.05vs0.47±0.03,0.61±0.03,0.21±0.02;40d:1.01±0.14vs0.64±0.08,0.75±0.04,0.23±0.03;均P<0.05),OP组和OT组在40d时胰腺组织TβRⅡ的表达均比20d时明显增高(0.64±0.08vs0.47±0.03;0.75±0.04vs0.61±0.03;均P<0.05).结论:腹腔注射DDC建立大鼠胰腺纤维化模型,方法有效.OM有显著的抗胰腺纤维化作用,可能与其降低TβRⅡ含量,抑制TGF-β信号转导通路有关.

转化生长因子-β受体Ⅱ在增生性玻璃体视网膜病变增生膜中的表达

目的:观察及评估转化生长因子-β受体Ⅱ(TGF-βRⅡ)在增生性玻璃体视网膜病变(PVR)增生膜中的表达及临床意义。 方法:采用免疫组化和原位杂交方法,对13例PVR患者行玻璃体手术增生膜获得的16例进行TGF-βRⅡ的蛋白和mRNA的检测。 结果:免疫组化结果为:9例C2～C3级膜中,染色反应为阳性的有8例,总阳性率为88.9％。7例D1～D3级膜中有6例为阳性,总阳性率为85.7％。阳性细胞多是一类胞体为长圆形,胞核呈圆形或卵圆形的上皮样细胞。统计学分析TGF-βRⅡ标记与膜分级间无相关性(P>0.05)。原位杂交结果与免疫组化基本一致。 结论:PVR发生过程中视网膜色素上皮细胞在生长因子等的刺激下,TGF-βRⅡ表达显著上调,表明了TGF-β参与PVR增生膜的形成。眼科学报 2003;19:244-247。

转化生长因子β受体Ⅱ在大鼠实验性隐睾中的表达及与生精细胞凋亡的关系

目的:探讨转化生长因子β受体Ⅱ(TGFβ-RⅡ)与实验性隐睾诱导的生精细胞凋亡的关系。方法:建立大鼠单侧隐睾动物模型,SABC法检测TGFβ-RⅡ在隐睾及对照侧睾丸组织内的分布及表达,TUNEL法检测凋亡生精细胞。结果:术后不同时间组隐睾侧曲细精管TGFβ-RⅡ表达均低于对照侧(P<0.01)。术后隐睾侧细胞凋亡数量较对照侧明显增加(P<0.01)。结论:TGFβ可能通过TGFβ-RⅡ介导的信号转导过程在睾丸生精细胞凋亡过程中发挥重要的调控作用。

TGF-βⅡ型受体与Fn在小鼠肾泌尿小管发育中的表达

目的观察转化生长因子βⅡ型受体(TGF-βRⅡ)及纤维连接蛋白(Fn)在小鼠肾泌尿小管发育中的时空性表达,探讨TGF-βRⅡ和Fn与泌尿小管发育的关系。方法采用免疫组织化学技术结合体视学方法,测定不同胚龄(E12、14、16、18 d)及生后日龄(P1、3、7、14、21、28、42 d)小鼠肾泌尿小管TGF-βRⅡ和Fn的表达及其含量变化。结果TGF-βRⅡ在各期肾小管及集合管内均有表达,其表达量随着发育逐渐增加,但在各期近端小管强烈表达,各期集合管表达较强,而各期远端小管表达较弱;Fn在各期肾小管、集合管的基底膜处均有表达,其表达量随着发育逐渐增加。结论TGF-β和Fn可能对小鼠肾泌尿小管的发育以及成熟泌尿小管结构的维持起重要作用。

EMT、TGF-β_1、Ang Ⅱ与器官纤维化发生机制的研究进展

纤维化是大多数慢性炎症性疾病的病理转归,几乎能发生在身体的每个组织器官。纤维化以过多的细胞外基质沉积为特征,进一步发展可导致器官功能衰竭乃至死亡。关于器官纤维化的研究很多,但其确切机制目前尚不明确。近年来,上皮间质转化(EMT)、转化生长因子β1(TGF-β1)、血管紧张素Ⅱ(AngⅡ)在组织器官纤维化形成机制研究中备受关注。该文就EMT、TGF-β1、AngⅡ与各器官纤维化的相互关系及作用机制予以综述,以更全面地认识纤维化的发生机制。

TGF-β1/TGF-βRⅡ和Smad4在葡萄膜黑色素瘤中的表达

目的探讨转化生长因子β1(TGF-β1)/转化生长因子β受体Ⅱ(TGF-βRⅡ)和Smad4在葡萄膜黑色素瘤中的表达以及它们在葡萄膜黑色素瘤发病过程中可能的机制。方法应用免疫组织化学SP法检测TGF-β1/TGF-βRⅡ和Smad4在24例葡萄膜黑色素瘤瘤组织石蜡切片中的表达,并累计其表达的阳性率。结果24例葡萄膜黑色素瘤组织切片中,可见瘤组织TGF-β1阳性率为24/24,TGF-βRⅡ阳性率12/24,Smad4阳性率11/24,后两者双阳性率为5/24。结论葡萄膜黑色素瘤组织中TGF-β1表达高于瘤旁组织;TGF-βRⅡ和(或)Smad4的表达异常与葡萄膜黑色素瘤发病有关。