TGF-β1和TGF-α在膀胱癌侵袭和转移中的作用

目的 探讨转化生长因子-β（TGF-β1）和转化生长因子－α（TGF-α）对膀胱癌细胞株（EJ）生长的影响以及促进膀胱癌侵袭和转移的可能途径。方法 采用MTT、Western Blot和RT－PCR方法,观察TGF－β1和TGF－α对DJ细胞株生长以及在mRNA和蛋白水平上对金属基质蛋白酶（MMPs)和组织特异性金属蛋白酶抑制剂－2（TIMP－2）表达的影响。结果 （1）TGF-β1和TGF－α对EJ细胞生长存在抑制趋势,但差别无显著性意义。（2）TGF－β1和TGF－α作用于EJ细胞48h时 ,MMP－2、TIMP－2、MT1－MMP mRNA表达降低;TGF－β1组MMP-9 mRNA表达增加,而对照组和TGF－α组无MP－9mRNA表达。（3）当TGF－β1浓度为0．1、1．0ng/ml时,增加细胞培养上清液中MMP－2蛋白含量对TIMP－2蛋白水平无影响。当浓度为5．0、10．0ng/ml时对MMP－2无影响而降低TIMP－2表达;TGF－α在浓度为1.0、5.0、10.0ng/ml时,对MMP－2蛋白表达无影响而降低TIMP－2表达;在100．0ng/ml时增加MMP－2蛋白表达而对TIMP－2表达无影响;无论在对照组和实验组均未检测到MMP－9。结论 TGF-β1、TGF-α不能抑制EJ细胞生长,参与肿瘤侵袭和转移作用可能与调节MMPs、TIMP－2表达途径有关。     

胃癌组织smad4基因和转化生长因子β1及其受体的表达及意义

目的 研究胃癌组织中smad4 mRNA、转化生长因子β、（TGF－β1）、转化生长因子β1受体（TGF－βR1）的表达特征及其意义。方法 常规石蜡包埋切片行smad4 mRNA原位杂交染色及TGF－β1、TGF－βR1免疫组织化学染色。结果 smad4 mRNA、TGF－β1、TGF－βR1在胃腺癌、黏液腺癌和印戒细胞癌中阳性率无明显差异;组织学分级I组、癌细胞未浸润至深肌层和淋巴结未转移的组织smad4 mRNA、TGF-β1、TGF－βR1阳性率明显高于组织学分级Ⅲ级、癌细胞浸润至深肌层或浆膜层和淋巴结转移组织,差异均有显或非常显性意义;smad4 mRNA、TGF－β1、TGF－βR1在胃癌中表达密切相关。结论 smad4 mRNA、TGF－β1和TGF－βR1 3表达与胃癌发生发展、生物学行为和预后可能有关,可作为重要的生物学标记物。     

性激素受体及相关生长因子在前列腺基质细胞中的表达

目的：探讨前列腺基质增生的发病机制与性激素以及相关生长因子的关系。方法：应用RT－PCR的方法研究了在人前列腺不同细胞类型中Smoothelin的表达，研究了雄、雌激素受体及相关生长因子在前列腺基质细胞中的表达，以及它们在前列腺基质细胞分化中表达的变化。结果：Smoothelin是前列腺平滑肌细胞特异性的标记蛋白；雄激素受体（AR）、碱性成纤维细胞生长因子（bFGF)、角化细胞生长因子（KGF）主要在前列腺成纤维细胞中表达，而雌激素受体（ER）、转移生长因子β1（TGFβ1）主要在平滑肌细胞中表达。结论：前列腺基质增生与雌激素受体和转移生长因子β1的过度表达密切相关。     

不同免疫抑制剂对大鼠血管平滑肌细胞转化生长因子-β1和Smads信号通路的影响及意义

目的研究不同免疫抑制剂对大鼠血管平滑肌细胞（VSMC）转化生长因子（TGF）-β1和Smacks信号通路的影响，探讨其在慢性移植肾肾病发生、发展中的作用。方法应用大鼠胸主动脉平滑肌细胞体外原代培养技术，分别用CsA（3mg／L）、FK506（1mg／L）、MMF（0．3mg／L）与RPM（10mg／L）处理6、12h。用免疫组织化学和实时荧光定量聚合酶链反应检测TGF—β1、Smacks蛋白和mRNA在平滑肌细胞中的表达及定位。结果CsA组和FK506组TGF—β1、Smad2的蛋白和mRNA表达水平高于对照组、MMF组和RPM组（P〈0．01），Smad7蛋白和mRNA表达低于对照组、MMF组和RPM组（P〈0．01）；MMF组和RAPA组TGF-β1、Smad2蛋白和mRNA表达低于对照组（P〈0．01），而Smad7的表达高于对照组（P〈0．01）。CsA组和FK506组，以及MMF组和RPM组的组间差异无统计学意义（P〉0．05）。结论不同免疫抑制剂可能通过影响血管平滑肌细胞TGF—β1和Smacks信号通路，导致移植物动脉硬化，从而影响慢性移植肾功能丧失的进程。     

转化生长因子-β和碱性成纤维细胞因子在儿童原发性局灶节段性肾小球硬化肾组织中的表达

目的：通过检测转化生长因子-β（TGF-β）和碱性成纤维细胞生长因子（bFGF）在儿童原发性局灶节段性肾小球硬化（FSGS）肾组织中的表达情况,并分析其与肾小管间质病理变化的关系,以了解TGF-β与bFGF在原发性FSGS发生发展中的作用。方法：选择肾活检明确诊断为原发性FSGS患儿的肾组织共43例,其中不伴有肾小管间质病变的FSGS肾组织共16例,设为实验1组;伴有肾小管间质病变的FSGS肾组织共27例,为实验2组。另将同期因孤立性血尿入院肾活检证实为非FSGS、病理改变较轻的肾组织作为对照组,共17例。采用免疫组化法检测细胞/生长因子TGF-β、bFGF在各组中的表达。通过方差分析（ANOVA）和相关分析法分析细胞/生长因子的表达与FSGS肾组织病理变化的关系以及细胞/生长因子之间的相互作用关系。结果：TGF-β、bFGF在各组肾组织中均有表达,表达量在对照组、实验1组和实验2组中依次升高,各组间的差异均具有统计学意义（P〈0.05）;且TGF-β和bFGF的表达与肾小管间质指数呈正相关,相关系数依次为0.763和0.661。此外,TGF-β和bFGF两者的表达量经相关分析也显示呈正相关,相关系数为0.587。结论：TGF-β和bFGF在原发性FSGS患儿肾组织中高表达;随着FSGS的发展,它们在肾组织中表达量不断增加,促使肾小管间质向纤维化发展,而且两者在促进肾脏纤维化具有一定的协同作用。     

水蛭素对皮肤增生性瘢痕成纤维细胞bFGF及TGFβ_1表达的影响

目的：检测水蛭素对人皮肤瘢痕成纤维细胞碱性成纤维细胞因子（basic fibroblast growth factor,bFGF）、转化生长因子β1（transforming growth factor beta 1,TGFβ1）表达的影响,探讨水蛭素抑制瘢痕形成的作用及机制。方法：体外培养并鉴定人皮肤瘢痕成纤维细胞,实时荧光定量RT-PCR和免疫细胞化学法分别检测不同浓度水蛭素作用人成纤维细胞24h后,bFGF、TGFβ1的mRNA和bFGF、TGFβ1蛋白表达水平。结果：浓度为0.156～2.5 U/L的水蛭素可下调瘢痕成纤维细胞TGFβ1mRNA、蛋白的表达,同时上调bFGF的mRNA、蛋白的表达,不同浓度组间比较,差异有统计学意义。水蛭素可抑制增生性瘢痕成纤维细胞分泌TGFβ1,促进其分泌bFGF。结论：水蛭素抑制瘢痕可调节bFGF、TGFβ1分泌,由此抑制成纤维细胞的生长、增殖并进一步抑制瘢痕形成。     

转移生长因子-β、碱性成纤维细胞生长因子诱导人成骨细胞表达血小板衍生生长因子BmRNA的研究

目的　探讨转移生长因子（TGF）-β、碱性成纤维细胞生长因子（bFGF）对人成骨细胞血小板衍生生长因子（PDGF）-B mRNA表达的影响及其意义。方法　体外分离培养人成骨细胞。在体外培养的成骨细胞中分别加入10、20、40、80、160 μg/L梯度浓度的PDGF-BB培养细胞24 h,以摄取3H-TdR为细胞增殖指标检测细胞增殖状况。以4 μg /L的TGF-β和10 μg/L的bFGF培养细胞24 h,寡核苷酸探针检测细胞PDGF-B mRNA的表达。 结果　10～160 μg/L的PDGF-BB可促进成骨细胞增殖（P＜0.05）。在普通培养条件下,细胞不表达PDGF-B mRNA;当培养体系中加入TGF-β和bFGF,可见PDGF-B mRNA的表达。 结论　PDGF-B基因的表达可能是骨组织生长的储备因素,TGF-β和bFGF可诱导成骨细胞表达PDGF-BB。     

甲状旁腺激素促进系膜细胞合成分泌转化生长因子β1

目的：研究甲状旁腺激素（PTH）对大鼠系膜细胞合成与分泌转化生长因子β1（TGF－β1）的影响。方法：（1）分别以10^-12,10^-11,10^-10,10^-9,10^-8mol/l的hPTH1-34刺激大鼠系膜细胞6，12，24，48h后，ELISA方法测定上清中TGF－β1的浓度；（2）分别以10^-12,10^-11,10^-10,10^-9,10^-8mol/L的hPTH1-34刺激大鼠系细胞48h,采用半定量RT－PCR方法检测细胞TGF－β1 mRNA的表达；（3）以10^-8mol/L的hPTH1-34分别刺激大鼠系膜细胞6，12，24，48h，采用半定量RT－PCR方法检测细胞TGF－β1 mRNA的表达，结果：（1）ELISA结果显示，hPTH1-34促进大鼠系膜细胞合成与分泌TGF－β1分泌作用达高峰（P＜0．01），（2）半定量RT－PCR方法结果显示，hPTH1-34促进大鼠系膜细胞TGF－β1 mRNA的表达，并具有浓度依赖和时间依赖性特点（各组与对照组间P＜0．05），结论：hPTH1-34从蛋白和基因水平显著促进系膜细胞TGF－β1的合成与分泌，且呈浓度依赖和时间依赖性特点。     

良性增生前列腺组织中TGFβ1mRNA和蛋白的表达

目的：在转录和翻译水平探讨转化生长因子β1（TGFβ1）在良性前列腺增生症（BPH）前列腺组织中的表达及意义。方法：应用原位杂交和 免疫组织化学法对22例BPH和10例正常前列腺（NP）组织标本中TGFβ1的表达进行定性、定位检测。结果：BPH前列腺和NP组织的上皮和间质都有明显的TGFβ1mRNA表达,其表达在BPH和NP间差异无显著性意义（P＞0．05）;在两组间,基质细胞TGFβ1mRNA表达明显高于上皮细胞（P＜0．01）。BPH前列腺和NP的上皮组织中TGFβ1蛋白表达较弱,且两者之间差异无显著性意义（P＞0．05）;间质中TGFβ1表达均为阳性,BPH前列腺间质中阳性表达显著强于NP的间质（P＜0．01）,以基质为主要成分的增生结节中表达更高。结论：TGFβ1是导致BPH前列腺间质增生的重要物质,启动BPH发生发展的因素在转录后水平调控TGFβ1的表达。     

转化生长因子β1和结缔组织生长因子在狼疮肾炎肾小管间质中的表达

目的 研究狼疮性肾炎肾小管间质转化生长因子β1（TGF－β1）和结缔组织生长因子（CTGF）的表达特点及其意义。方法 应用免疫组织化学方法比较原发性肾小球肾炎微小病变型（MCD）和狼疮肾炎（LN）肾小管间质中TGF－β1和CTGF的表达及分布以及浸润细胞，α－平滑肌肌动蛋白（SMA）的表达特点。结果 TGF－β1及CTGF可不同程度地表达于LN的肾小球和肾小管间质，且较MCD的表达普遍增高，肾间质TGF－β1表达量与CTGF的表达量之间的相关系数r=0.5316,P=0.023。LN患者肾间质内CD3阳性细胞，CD68阳性细胞，PCNA阳性细胞以及α－SMA的表达明显高于MCD患者。α－SMA的表达程度与肾小管间质纤维化程度存在正相关关系，r=0.436,P=0.032。结论 LN肾间质内TGF－β1和CTGF表达增高，可能与LN肾间质病变及炎性细胞的浸润有关。     

膀胱出口梗阻大鼠逼尿肌中神经生长因子mRNA的变化及其意义

目的探讨膀胱出口梗阻(BOO)大鼠模型膀胱逼尿肌中神经生长因子(NGF)mR- NA的表达变化及意义。方法建立BOO大鼠模型,采用逆转录-聚合酶链反应(RT-PER)检测大鼠膀胱逼尿肌中NGF mRNA的表达。结果:NGF mRNA在模型组和对照组的膀胱逼尿肌细胞中均有表达,模型组大鼠的逼尿肌NGF mRNA水平高于对照组,两组间的mRNA平均水平差异有统计学意义(P<0.01)。结论膀胱出口梗阻后,膀胱逼尿肌细胞中NGF mRNA表达水平增高,这可能与BOO所致膀胱功能受损的发生有关。     

前列腺增生症所致膀胱出口梗阻患者逼尿肌中神经生长因子mRNA的变化及意义

目的　探讨前列腺增生症 (BPH)所致膀胱出口梗阻 (BOO)患者膀胱逼尿肌中神经生长因子 (NGF)mRNA的表达变化及意义。方法　对同龄对照组 8例膀胱癌患者、BPH梗阻逼尿肌稳定组 2 4例患者和BPH梗阻逼尿肌不稳定组 16例患者的膀胱壁逼尿肌组织 ,采用逆转录聚合酶链反应(RT PCR)检测膀胱逼尿肌细胞中NGFmRNA的表达。结果　NGFmRNA在同龄对照组、BPH梗阻逼尿肌稳定组和梗阻逼尿肌不稳定组患者的膀胱逼尿肌细胞中均有表达 ,三组患者的平均表达水平两两之间差异均有显著性意义 (P <0 0 1) ,而且NGFmRNA在同龄对照组、BPH梗阻逼尿肌稳定组和梗阻逼尿肌不稳定组的平均表达水平逐渐增加。结论　前列腺增生症引起膀胱出口梗阻后 ,膀胱逼尿肌细胞中NGFmRNA表达水平增高 ,并可能与逼尿肌不稳定 (DI)的发生有关。     

Expression of transforming growth factor beta1 gene, basic fibroblast growth factor gene and hydroxyproline in diabetes-induced bladder dysfunction in a rat model

AIMS: To investigate the content of hydroxyproline (Hyp) and the expression of transforming growth factor beta1 (TGF beta1) and basic fibroblast growth factor (bFGF) in the bladder 8 weeks after diabetes induction. METHODS: Thirty wistar rats were divided into three groups: control (n = 10), streptozotocin-induced diabetic group (n = 10), TAD group (n = 10; diabetic rats were fed with Tadenan 100 mg kg(-1) day(-1)). Eight weeks later, the bladders were dissected. RT-PCR, immunohistochemistry, and ELISA were used to detect the expression of TGF beta1 and bFGF in the bladder. Also hydroxyproline (Hyp) was measured using a method based on alkaline hydrolysis. RESULTS: The content of hydroxyproline in the diabetic group was greater than that of control group (P < 0.05); we found significantly increased expression of TGF beta1 mRNA and bFGF mRNA in the bladder from the diabetic group compared with the control group; immunohistochemical and ELISA studies showed a statistically significant increased expression of TGF beta1 protein and bFGF protein in the bladder from the diabetic group compared with the control group (P < 0.05). The content of hydroxyproline in TAD group was less than that of diabetic group (P < 0.05); mRNA expression of TGF beta1 and bFGF greatly decreased in TAD group compared with that of the diabetic group; immunohistochemical and ELISA studies showed decreased levels of TGF beta1 protein and bFGF protein in the bladder from TAD group compared with the diabetic group (P < 0.05). CONCLUSIONS: Rats with streptozoticin-induced diabetes mellitus showed significant increase in hydroxyproline, TGF beta1 and bFGF levels in their bladders, which may be an important mechanism inducing diabetic cystopathy. Tadenan could effectively reduce hydroxyproline, TGF beta1, and bFGF levels.     

膀胱出口部分梗阻早期结缔组织生长因子的表达及意义

目的 研究结缔组织生长因子(CTGF)在大鼠膀胱出口部分梗阻(B00)致膀胱重塑时早期各时相在逼尿肌中的表达.方法 Wistar大鼠36只随机分为3组:梗阻7d组、梗阻14d组及对照组,每组12只.按设计,各时段获取膀胱标本,测量其重量及最大膀胱容量.用逆转录-聚合酶链反应(RT-PCR)半定量法测定膀胱逼尿肌的CTGF mRNA.CTGF相关蛋白定位、定性诊断实验用免疫组织化学法.结果 梗阻14 d组(B002组)、梗阻7 d组(B001组)的CTGFmRNA相对峰值分别为0.99±0.58、0.84±0.12.两组比较差异有统计学意义(P＜0.05).B002组、B001组膀胱重量分别为(241.08±4.36)、(237.08±6.02)g,均高于对照组(158.50±4.62)g(P＜0.05).B002组、B001组膀胱容量分别为(0.82±0.03)、(0.74±0.03)ml,均高于对照组(0.62±0.02)ml(P＜0.05).免疫组织化学结果提示:B001组(3/12)及B002组的标本部分或全部免疫染色,显色区分布在黏膜下固有层或平滑肌肌束间.对照组无1例染色.结论 CTGF是PB00膀胱纤维化早期过程中重要的调节因子.     

Effect of peritoneal dialysis on expression of vascular endothelial growth factor, basic fibroblast growth factor and endostatin of the peritoneum in peritoneal dialysis patients

Aim: The aim of this study is to investigate the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and endostatin (ES) in human peritoneum and investigate the relationship between them and peritoneum neoangiogensis in the patients with uraemia and peritoneal dialysis (PD). Methods: Peritoneal biopsies were obtained from normal subjects (n = 8), uraemic predialysis patients (n = 12) and PD patients (n = 10). The mRNA expression of VEGF, bFGF and ES in peritoneal tissues were measured through real‐time polymerase chain reaction. The protein expression of VEGF, bFGF and ES in peritoneal tissues were determined through western blot. Microvessel density (MVD) of peritoneal tissue was assessed using immunohistochemistry with CD34 monoclonal antibody. Results: The mRNA and protein of VEGF, bFGF and ES were expressed in all peritoneal samples. Compared with the normal control group, the mRNA and protein expression of VEGF and bFGF in peritoneal tissues were all significantly upregulated in the uraemic predialysis and PD group (all P < 0.05). Compared with the normal control group, the protein expression of ES were significantly upregulated in the uraemic predialysis and PD group (all (P < 0.05), but the mRNA expression of ES did not have obvious differences in the uraemic predialysis and PD group as compared to the normal control group (P > 0.05). MVD of peritoneal tissue were increased in the uraemic predialysis and PD group compared with the normal group (all P < 0.05). A significant positive correlation was found between VEGF mRNA expression and MVD, bFGF mRNA expression and MVD. Conclusion: The mRNA expression of VEGF and bFGF, the protein expression of VEGF, bFGF, and ES and microvessel density (MVD) are increased both in the uraemic predialysis and PD patients. These results show that uraemia circumstances and non‐physiological compatibility of peritoneal dialysis solution might increase VEGF, bFGF and ES expression and MVD, which might participate in the increment of the peritoneum neoangiogensis and ultrafiltration failure in PD patients.     

Calcineurin mediates bladder smooth muscle hypertrophy after bladder outlet obstruction

PURPOSE: Bladder outlet obstruction (BOO) leads to compensatory bladder hypertrophy. However, the hypertrophy mechanism remains elusive. We report that calcineurin (Cn) is involved in bladder hypertrophy. MATERIALS AND METHODS: Partial BOO was surgically induced in 10-week-old female Wistar rats. The bladder was excised 2, 4 and 6 weeks following surgery in 9 rats each. Histological study was performed at each time point. Cn expression was examined by Western blot analysis. Myosin heavy chain expression was evaluated on gels stained with Coomassie blue. Primary cultured bladder smooth muscle cells were infected with recombinant adenoviruses encoding a constitutive active form of CnA (DeltaCnA), CnB and lacZ, and cell size was measured. RESULTS: In histological findings bladder smooth muscle hypertrophy was observed 2 and 4 weeks after surgery. However, the thickened muscles became thinner 6 weeks after BOO. CnA expression 2 weeks after BOO increased 3.2-fold compared with that of controls. Expression significantly decreased 4 and 6 weeks after surgery. In contrast, CnB expression was unchanged throughout hypertrophy development. Changes in myosin heavy chain expression correlated with changes in CnA. We observed significant hypertrophy in DeltaCnA and CnB over expressing smooth muscle cells. Moreover, FK506, which is a potent inhibitor of Cn, blocked hypertrophy in DeltaCnA and CnB over expressing smooth muscle cells. CONCLUSIONS: These data suggest that Cn has an important role in the induction of bladder smooth muscle hypertrophy.     

Muscarinic and purinergic receptor expression in the urothelium of rats with detrusor overactivity induced by bladder outlet obstruction

OBJECTIVE

To investigate the expression of muscarinic and purinergic receptors in rat urothelium, and changes in their distribution and expression following detrusor overactivity induced by bladder outlet obstruction (BOO).

MATERIALS AND METHODS

Thirty Sprague‐Dawley rats were divided into control (10) and BOO groups (20). Partial BOO was induced for 3 weeks and the rats assessed by cystometrography. A portion of the bladder was stained using immunofluorescence for M₂ and M₃ muscarinic receptors, and P2X₃ purinergic receptors. The remainder was dissected into bladder urothelium and the smooth muscle layer, and the expression of the receptor proteins analysed by Western blotting.

RESULTS

Cystometrography showed a significant decrease in contraction interval and increase in contraction pressure in the BOO group. On immunofluorescence staining, muscarinic and purinergic receptors were localized in both the urothelium and the muscle layer. Immunoreactivity of M₂ and M₃ muscarinic receptors was greater in the urothelium of the BOO group than in the control group; there was a smaller increase in P2X₃ immunoreactivity. On Western blotting, the expression of M₂, M₃ and P2X₃ receptors was increased in the urothelium of the BOO group, and there was increased M₃ receptor expression in the muscle layer of the BOO group.

CONCLUSIONS

There were detectable changes in muscarinic and purinergic receptors with bladder overactivity induced by BOO. Our results suggest that changes in urothelium receptor expression could have a role in mediating the afferent sensory responses in the urinary bladder.     

Expression of epidermal growth factor, basic fibroblast growth factor and insulin growth factor-1 and relation to myocyte regeneration of obstructed ureters in rats

OBJECTIVE: To investigate the roles of epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) and insulin growth factor-1 (IGF-1) in the myocyte regeneration of obstructed ureters. MATERIAL AND METHODS: The expression of EGF, bFGF, IGF-1 and proliferation cell nuclear antigen (PCNA) was studied immunohistochemically in 54 female Sprague-Dawley rats. RESULTS: Tissue damage to the smooth muscle layer in the obstructed ureters was aggravated during the period of obstruction. The expression of EGF, bFGF and IGF-1 in myocytes was detected using the method of concurrent immunohistochemical staining. The expression of EGF, bFGF and IGF-1 in the smooth muscle layer was found from Day 14 after ligation. The expression of EGF, bFGF and IGF-1 increased to a peak on Day 21 and then declined. The expression of PCNA in the smooth muscle layer was also found from Day 14 after ligation and increased to a peak on Day 21. The expressions of EGF, bFGF and IGF-1 were significantly correlated with the expression of PCNA in the smooth muscle layer (r=0.7982, 0.6264 and 0.5840, respectively; p-values all <0.002). Co-expression of EGF, bFGF, IGF-1 and PCNA was determined using the method of double immunofluorescence staining. Co-expression of PCNA was observed in 34% of EGF-positive myocytes, 53.6% of bFGF-positive myocytes and 41.1% of IGF-1-positive myocytes at Day 21 post-ligation. CONCLUSIONS: Expression of EGF, bFGF and IGF-1 may contribute to myocyte regeneration of damaged ureters in rats with obstructive uropathy.     

Possible role of endothelin-1 in the rabbit urinary bladder hyperplasia secondary to partial bladder outlet obstruction

OBJECTIVES: Urinary bladder hypertrophy and hyperplasia are common features of bladder outlet obstruction (BOO). The urinary bladder is known to synthesize endothelin-1 (ET-1), which is a potent vasoconstrictor peptide with mitogenic properties. Using an animal model of partial BOO, we investigated the potential role of ET-1 and its receptor subtypes (ET(A) and ET(B)) in bladder smooth muscle cell (SMC) proliferation. MATERIALS AND METHODS: Partial BOO was produced in adult male New Zealand White rabbits. After 3 weeks, the bladder was removed and SMCs from the dome and bladder neck were grown using standard explant methodology. At passage 2, the cells were made quiescent and then further incubated in foetal calf serum (FCS), control age-matched rabbit serum (CRS) or partial BOO serum (BRS) in the presence or absence of ET(A)-antagonist (BQ123) or ET(B)-antagonist (BQ788). SMC proliferation was then measured 24 h later with 5-bromo-2'deoxy-uracil and by cell counting using a haemocytometer at 48 h. Immunostaining for alpha-actin was performed on detrusor and bladder neck cells to confirm the presence of smooth muscle cells. RESULTS: BQ123 and BQ788 did not influence detrusor or bladder neck SMC proliferation in FCS or CRS. However, in the presence of BRS, BQ123 and BQ788 (100 nmol/L) significantly (p = 0.008) inhibited detrusor and bladder neck SMC proliferation. Cell counts were significantly reduced from the detrusor (p = 0.03, p = 0.01 with BQ123 and BQ788, respectively) and bladder neck (p = 0.01 for both BQ123 and BQ78). CONCLUSIONS: These results suggest that ET antagonists may have a role in preventing SMC hyperplasia associated with partial BOO.