整合素连接激酶和肾小管-间质纤维化

整合素连接激酶(Integrin-linkedkinase,ILK)是一种近期发现的Ser/Thr蛋白激酶。ILK能够通过与整合素β1亚单位的结合介导细胞与胞外基质的连接,以依赖于PI3K的方式激活,并通过磷酸化下游底物PKB/AKT、GSK3等使胞外信号得以向下游传递,参与多种信号传导通路,与肾间质纤维化的发生相关。     

整合素连接激酶和肾小管-间质纤维化

整合素连接激酶(Integrin-linked kinase,ILK)是一种近期发现的Ser/Thr蛋白激酶.ILK能够通过与整合素β1亚单位的结合介导细胞与胞外基质的连接,以依赖于PI3K的方式激活,并通过磷酸化下游底物PKB/AKT、GSK3等使胞外信号得以向下游传递,参与多种信号传导通路,与肾间质纤维化的发生相关.     

整合素连接激酶介导的高糖诱导肾小管上皮细胞纤连蛋白的表达

目的 观察在高糖刺激下纤连蛋白（FN）与整合素连接激酶(ILK) 在肾小管上皮细胞的表达情况，探讨糖尿病肾病小管间质纤维化的发病机制。 方法 以人肾小管上皮细胞株（HKC）细胞和链脲佐菌素（STZ）诱导的CD-1小鼠糖尿病动物模型为研究对象，采用Western印迹的方法检测细胞或肾组织ILK和FN蛋白的表达。通过基因转染的方法，将含无激酶活力的人ILK基因表达质粒pCMV-kdILK转染HKC细胞，观察抑制ILK活力对高糖诱导的HKC合成FN的影响。 结果 STZ注射后4周，CD-1小鼠血糖水平显著高于对照组[(20.3±2.7) mmol/L比 （6.1±1.4） mmol/L，P < 0.01]，同时，肾组织ILK和FN的表达量亦显著高于对照组，且ILK与FN表达量呈正相关(P < 0.01)。细胞培养实验证实，高糖能够刺激HKC上调ILK和FN蛋白的表达，并且呈时间和剂量依赖性。HKC细胞转染pCMV-kdILK质粒以抑制ILK的活力，能够显著地拮抗高糖刺激HKC表达FN的作用。 结论 高糖通过上调ILK蛋白增加肾小管表达并合成FN，抑制ILK能够拮抗高糖刺激HKC合成FN的作用。     

缬沙坦对糖尿病肾病大鼠肾小管上皮细胞整合素连接激酶表达的影响

目的：观察缬沙坦对糖尿病肾病（DN）大鼠肾小管上皮细胞整合素连接激酶（ILK）表达的影响，探讨缬沙坦肾脏保护作用的可能机制。方法：30只Wistar雄性大鼠随机分为正常组（n=10）、模型组（n=10）和干预组（缬沙坦30mg·kg^-1·d^-1，n=10）。第8、16周每组各处死5只大鼠，观察大鼠肾脏病理改变以及免疫组化方法检测其肾小管上皮细胞转化生长因子-β1（TGF-β1）、ILK的表达并作半定量分析。结果：（1）DN大鼠肾小管上皮细胞ILK与TGF-β1同向表达增高，随病程进展递增；（2）缬沙坦干预后大鼠肾小管上皮细胞ILK表达较模型组显著降低。结论：（1）DN大鼠肾小管上皮细胞ILK与TGF-β1同向表达增高，提示ILK是肾间质纤维化发展的一个重要因素；（2）缬沙坦可能通过下调ILK来改善肾间质纤维化病变而发挥肾脏保护作用。     

依贝沙坦对单侧输尿管梗阻小鼠肾脏整合素连接激酶表达的影响及意义

目的研究依贝沙坦（Irb）对单侧输尿管梗阻（UUO）小鼠肾脏整合素连接激酶（ILK）表达的影响,并探讨其与肾小管上皮间充质转化的关系。方法将雄性CD-1小鼠随机分为假手术对照组（C,n=20）、UUO组（UUO,n=40）和Irb治疗组（UUO＋Irb,n=40）,分别于术后1、3、7和14d处死小鼠。Masson染色观察肾间质纤维化。免疫组化检测小鼠肾组织ILK、上皮细胞钙黏蛋白（E-cadherin）和α平滑肌肌动蛋白（α-SMA）表达。Western印迹观察小鼠肾组织ILK蛋白表达。荧光实时定量PCR（real-time PCR）检测ILK、E-cadherin、α-SMA和纤连蛋白（FN）mRNA表达。结果与C组相比,UUO组术后1d ILK mRNA及蛋白表达均增高;术后3d FN mRNA表达上调,E-cadherin mRNA及蛋白表达明显减少,α-SMA mRNA及蛋白表达显著增加。与UUO组相同时间点比较,Irb治疗组ILK、FN及α-SMA表达均被显著抑制（P均＜0．05）;E-cadherin表达则增高（P＜0．01）。ILK蛋白表达与α-SMA蛋白表达呈正相关（r =0．707,P＜0．01）,与E-cadherin蛋白表达呈负相关（r=-0．919,P＜0．01）。结论Irb能减轻肾脏纤维化,抑制肾小管上皮细胞转分化,这可能与其抑制肾小管细胞ILK表达有关。     

糖尿病大鼠肾小管整合素连接激酶的表达及氯沙坦的干预作用

目的：观察糖尿病大鼠肾小管上皮细胞整合素连接激酶（ILK）的表达以及氯沙坦对其的影响。方法：雄性Wistar大鼠腹腔内注射链脲佐菌素（STZ）诱导糖尿病模型,随机分为模型组和氯沙坦组;另设正常组腹腔注射缓冲液。第8周、第16周测24h尿蛋白定量和血肌酐,处死大鼠,取肾组织行HE、Masson染色,观察肾脏病理改变;免疫组化法检测大鼠肾小管上皮细胞ILK、TGF-β1的表达。结果：模型组大鼠肾小管上皮细胞胞浆ILK表达增高,与小管间质病变程度一致;同时TGF-β1表达亦增高,并与ILK表达呈正相关性。氯沙坦组大鼠尿蛋白较模型组明显减少,肾小管间质病变减轻,肾小管上皮细胞ILK、TGF-β1表达明显减弱。结论：糖尿病大鼠肾小管上皮细胞存在有ILK的高表达,ILK的表达强度与肾小管间质损伤程度相一致,并与TGF-β1的表达呈正相关;氯沙坦能下调肾小管上皮细胞ILK的表达。     

结缔组织生长因子对人肾小管上皮细胞转分化影响的研究

目的 探讨结缔组织生长因子(CTGF)在人类肾小管上皮细胞转分化中的作用。方法 将体外培养的人近曲小管上皮细胞(HKC)分为3组:(1)对照组;(2)小剂量CTGF组:培养液中加入重组人CTGF(rhCTGF),终浓度为2.5ng/ml;(3)大剂量CTGF组:rhCTGF终浓度为5.0ng/ml。用逆转录-聚合酶链反应(RT-PCR)技术测定HKCα-平滑肌肌动蛋白(α-SMA)和纤连蛋白(FN)mRNA水平的变化。间接免疫荧光方法检测HKC α-SMA的表达。流式细胞仪检测α-SMA阳性细胞百分率。ELISA方法测定培养液上清中FN的浓度。结果 不同浓度rhCTGF作用于HKC 24h后,α-SMA和FN mRNA水平显著升高(P<0.01)。刺激48h后,胞浆α-SMA蛋白表达明显增强,流式细胞仪测得3组细胞α-SMA阳性百分率依次为:2.4%、38.9%、65.5%(P<0.01);ELISA结果显示,rhCTGF能促进HKC分泌FN,且呈剂量依赖性(P<0.01)。结论 CTGF在体外能刺激肾小管上皮细胞向肌成纤维细胞(MyoF)转分化,并促进其合成细胞外基质(ECM)。     

黏着斑激酶在转化生长因子β1诱导的人肾小管上皮细胞转分化中的作用

目的 观察转化生长因子（TGF）β1诱导的正常人近端肾小管上皮细胞（HK-2）转分化（EMT）过程中黏着斑激酶（FAK）的表达及下调FAK的表达后对TGF-β1诱导的HK-2细胞转分化进程的影响。 方法 应用TGF-β1（10 μg/L）刺激HK-2细胞,采用RT-PCR、Western印迹和免疫荧光方法分别检测E钙黏蛋白（E-cadherin）、α平滑肌肌动蛋白（α-SMA）、FAK mRNA和蛋白的表达及磷酸化（p）-FAK（Tyr397）的蛋白表达。应用Lipofectmine2000将FAK siRNA转染HK-2细胞,采用Western印迹观察下调表达FAK对上述指标的影响。 结果 TGF-β1刺激后,HK-2细胞α-SMA蛋白和mRNA水平上调,E-cadherin蛋白和mRNA表达下调。FAK蛋白和mRNA随时间的延长表达逐渐增多,48 h达到高峰。p-FAK（Tyr397）蛋白表达趋势与FAK相同。脂质体转染siRNA后FAK的mRNA和蛋白分别下调了50%和41%,下调表达FAK后可以显著抑制TGF-β1诱导的HK-2细胞α-SMA蛋白的上调表达,逆转 E-cadherin蛋白的下调表达。 结论 在TGF-β1诱导的HK-2细胞转分化进程FAK蛋白表达上调,敲低FAK蛋白表达后可以部分减轻EMT的程度,提示FAK在TGF-β1诱导的肾小管上皮细胞转分化和肾脏纤维化中发挥一定的作用。     

晚期糖基化终产物诱导人肾小管上皮细胞表达结缔组织生长因子

目的观察晚期糖基化终产物（AGE）修饰的牛血清白蛋白（BSA）对体外培养的人近端肾小管上皮细胞株（HK-2细胞）表达结缔组织生长因子（CTGF）的影响，并探讨可能的作用途径。方法将HK-2细胞在体外与不同浓度的AGE-BSA和BSA共同培养。间接免疫荧光法检测糖基化终产物受体（RAGE）。免疫印迹法观察HK-2细胞表达的CTGF蛋白质，ELISA和免疫印迹法检测TGF-β1的合成和分泌。结果在HK-2细胞的胞膜和胞质存在RAGE的表达。AGE-BSA以时间和剂量依赖方式上调HK-2细胞CTGF的表达，8、24、48及72h组分别为0h组的117％、138％、257％及339％：20、50及100mg／L组分别为0mg／L组的186％、240％及287％。在一定的剂量和时间范围内，AGE—BSA能够诱导TGF-β1蛋白质的表达和分泌。抗RAGE和抗TGF-β1的单克隆抗体能够部分抑制AGE-BSA诱导的CTGF蛋白质表达。结论人肾小管上皮细胞表面存在RAGE的表达。AGE—BSA可能部分地通过RAGE介导TGF-β1表达上调。诱导HK-2细胞CTGF表达。     

整合素连锁激酶介导转化生长因子β1上调肾小管上皮细胞表达纤连蛋白的研究

目的 研究转化生长因子β1（TGF-β1）诱导肾小管上皮细胞合成纤连蛋白（FN）与整合素连锁激酶（ILK）表达的关系.方法 培养人肾小管上皮细胞（HKC）,用蛋白印迹方法检测TGF-β1诱导HKC合成FN和表达ILK的作用.通过基因转染的方法,将含人野生型ILK基因的表达质粒pCMV-wtILK和无激酶活力的人ILK基因表达质粒pCMV-kdILK转染HKC细胞,观察ILK过度表达和抑制ILK活力对TGF-β1诱导的HKC合成FN的影响.结果 TGF-β1能够刺激HKC合成FN,其作用呈剂量依赖性.TGF-β1刺激8 h即可上调HKC细胞ILK的表达,与TGF-β1所致的FN合成的增加相一致.转染pCMV-wtILK质粒的HKC细胞,其FN的表达呈增加趋势.转染pCMV-kdILK抑制ILK的活力能够显著拮抗TGF-β1刺激HKC表达FN的作用.结论 TGF-β1刺激肾小管上皮细胞FN合成与其所致的ILK表达密切相关.抑制ILK的活力能够拮抗TGF-β1导致的FN合成.     

Connective tissue growth factor expression is increased in biliary epithelial cells in biliary atresia

Background/Purpose

Connective tissue growth factor (CTGF) has been implicated in the pathogenesis of hepatic fibrosis and is elevated in the serum of children with biliary atresia (BA). The objective of this study was to evaluate hepatic CTGF messenger RNA (mRNA) expression and its relationship to hepatic histology in children with BA.

Methods

Connective tissue growth factor mRNA expression was evaluated by in situ hybridization in 26 liver biopsies from 11 patients with BA, 11 with other diseases, and 4 autopsy controls. Serial sections were immunostained with cell-specific markers to characterize the cells expressing CTGF. Biopsies were scored for CTGF expression (0-4) and inflammation and fibrosis (1-4).

Results

High levels of CTGF expression were observed in 9 of 11 BA with localization to biliary epithelial cells and vascular endothelial cells. Connective tissue growth factor mRNA expression was correlated with fibrosis in BA and all livers. In the 11 patients with other liver diseases, 7 had CTGF expression limited to hepatic stellate cells and vascular endothelial cells. None of the 4 livers in children without liver disease had significant levels of CTGF.

Conclusions

In BA livers, novel biliary epithelia CTGF mRNA expression is high and correlates with severity of fibrosis. These data support a role for biliary epithelial cell signaling in fibrogenesis.     

甲状旁腺激素通过丝裂原活化蛋白激酶信号通路诱导人近曲小管上皮细胞结缔组织生长因子表达

目的 观察甲状旁腺激素（PTH）对人肾小管上皮细胞分泌结缔组织生长因子（CTGF）的影响，并探讨丝裂原活化蛋白激酶（MAPK）信号途径在此过程中的作用。 方法 采用实时定量PCR、Western印迹、报告基因等技术，观察PTH诱导人近端肾小管上皮细胞系HK-2细胞CTGF表达的情况。使用信号通路抑制剂PD98059、U0126阻断信号通路以明确PTH发挥作用的信号途径。 结果 正常HK-2细胞有基础水平的CTGF mRNA和蛋白表达，PTH刺激后其表达水平显著增加。10-10 mol/L PTH作用12 h后，荧光素酶活性较对照组明显升高[（1.8884±0.0780）比（0.9891±0.0300） A，P ＜ 0.01]。正常HK-2细胞有少量p-ERK1/2表达，PTH刺激后p-ERK1/2表达明显升高，以10-10 mol/L PTH作用30 min时效应最强；MAPK通路抑制剂PD98059、U0126作用后，CTGF mRNA、蛋白、基因启动子表达均明显下降。 结论 PTH可诱导HK-2细胞CTGF表达，其作用可能是通过MAPK信号通路来实现的。     

结缔组织生长因子影响体外培养瘢痕成纤维细胞ERK／MAPK信号通路活化及增殖的研究

目的探讨结缔组织生长因子（connective tissue growth factor,CTGF）诱导增生性瘢痕（hypertrophic scar,HS）成纤维细胞增殖的信号转导通路。方法采用。H-胸腺嘧啶核苷（^3H—TdR）掺入法观察不同浓度CTGF促HS成纤维细胞增殖的效应,以Western印迹法检测CTGF刺激HS成纤维细胞0、5、10、15、30、60min后,磷酸化及非磷酸化细胞外信号调节激酶1／2（extracellular-signal regulated kinase,ERK1／2）的表达,以两者的比值AI衡量信号通路活化程度;应用特异性阻断剂PD98059阻断ERK通路,MTT法检测CTGF诱导细胞增殖的变化。结果CTGF在一定浓度范围内呈浓度依赖性促HS成纤维细胞增殖,ERK1／2在无CTGF刺激时AI为0．0131±0．0036,CTGF刺激HS成纤维细胞5、10、15、30、60min后,AI值分别为0．0221±0．0033,0．1310±0．0361,0．2090±0．0201,0．1710±0．0379,0．0413±0．0036,在15min达高峰;采用PD98059选择性阻断ERK1／2通路后（A=0．420±0．046）与CTGF刺激组比较（A=0．660±0．035）,细胞增殖显著受到抑制（P〈0．01）。结论ERK1／2是CTGF诱导HS成纤维细胞增殖的主要活化的信号通路。     

金雀异黄素在甲状旁腺激素诱导的人近曲小管上皮细胞结缔组织生长因子表达中的调控作用

目的 探讨金雀异黄素（Gen）对甲状旁腺激素（PTH）引起的人近曲小管上皮细胞分泌结缔组织生长因子（CTGF）的调控作用。 方法 应用实时定量-聚合酶链反应（real time-PCR）、Western蛋白印迹、报告基因等技术,观察Gen对PTH诱导人近端肾小管上皮细胞系HK-2细胞CTGF表达的影响。使用MAPK通路抑制剂U0126阻断信号通路以明确Gen发挥作用的机制。 结果 HK-2细胞有基础量的CTGF mRNA和蛋白表达,PTH刺激后其表达量显著增加（P ＜ 0.05）。10-10 mol/L PTH作用12 h后,荧光素酶活性较对照组明显升高（1.8884±0.0780比0.9891±0.0300,P ＜ 0.01）。Gen剂量依赖性下调PTH诱导的HK-2细胞CTGF表达。正常HK-2细胞有少量磷酸化（p）ERK1/2表达,PTH刺激后p-ERK1/2表达明显升高,以10-10 mol/L PTH作用30 min时效应最强。U0126作用后,CTGF mRNA、蛋白表达均明显下降（P ＜ 0.05）。Gen抑制PTH所致的HK-2细胞ERK1/2活化。 结论 Gen可通过阻断MAPK信号通路抑制PTH诱导的HK-2细胞CTGF表达。     

结缔组织生长因子影响体外培养瘢痕成纤维细胞ERK/MAPK信号通路活化及增殖的研究

Objective To explore the signal mechanism of proliferation stimulating effect of connec-tive tissue growth factor (CTGF) on hypertrophic scar (HS) derived fibroblasts. Methods <'3>H-TdR in-corporation technique was used to determine the proliferative effect of CTGF at different concentration. Western blot was applied to semi-quantitively analyze the expression of phosphorylated and total ERK1/2 protein after 0, 5, 10, 15, 30, and 60 min of CTGF stimulation, and the relative value of which was de-fined as AI to measure the activation of ERK1/2 signal pathway. PD98059 was admitted to specifically block the ERK1/2 pathway, and subsequently cell proliferation stimulated by CTGF was studied by MTT. Results CTGF could stimulate fibroblasts proliferation with a dose-dependant manner, and activa-ted the ERK1/2 signal pathway, and AI built up to 0.209±0.0201, reaching the apex at 15 min after stimulation performed. Inhibition of ERK1/2 activation by PD98059 suppressed CTGF-mediated HS fi-broblasts proliferation significantly, while OD significantly dropped. Conclusion CTGF induces a prolif-erative response in HS fibroblasts, and this action is mainly dependent on the activation of ERK1/2 signal pathway.     

结缔组织生长因子影响体外培养瘢痕成纤维细胞ERK/MAPK信号通路活化及增殖的研究

Objective To explore the signal mechanism of proliferation stimulating effect of connec-tive tissue growth factor (CTGF) on hypertrophic scar (HS) derived fibroblasts. Methods <'3>H-TdR in-corporation technique was used to determine the proliferative effect of CTGF at different concentration. Western blot was applied to semi-quantitively analyze the expression of phosphorylated and total ERK1/2 protein after 0, 5, 10, 15, 30, and 60 min of CTGF stimulation, and the relative value of which was de-fined as AI to measure the activation of ERK1/2 signal pathway. PD98059 was admitted to specifically block the ERK1/2 pathway, and subsequently cell proliferation stimulated by CTGF was studied by MTT. Results CTGF could stimulate fibroblasts proliferation with a dose-dependant manner, and activa-ted the ERK1/2 signal pathway, and AI built up to 0.209±0.0201, reaching the apex at 15 min after stimulation performed. Inhibition of ERK1/2 activation by PD98059 suppressed CTGF-mediated HS fi-broblasts proliferation significantly, while OD significantly dropped. Conclusion CTGF induces a prolif-erative response in HS fibroblasts, and this action is mainly dependent on the activation of ERK1/2 signal pathway.     

结缔组织生长因子影响体外培养瘢痕成纤维细胞ERK/MAPK信号通路活化及增殖的研究

Objective To explore the signal mechanism of proliferation stimulating effect of connec-tive tissue growth factor (CTGF) on hypertrophic scar (HS) derived fibroblasts. Methods <'3>H-TdR in-corporation technique was used to determine the proliferative effect of CTGF at different concentration. Western blot was applied to semi-quantitively analyze the expression of phosphorylated and total ERK1/2 protein after 0, 5, 10, 15, 30, and 60 min of CTGF stimulation, and the relative value of which was de-fined as AI to measure the activation of ERK1/2 signal pathway. PD98059 was admitted to specifically block the ERK1/2 pathway, and subsequently cell proliferation stimulated by CTGF was studied by MTT. Results CTGF could stimulate fibroblasts proliferation with a dose-dependant manner, and activa-ted the ERK1/2 signal pathway, and AI built up to 0.209±0.0201, reaching the apex at 15 min after stimulation performed. Inhibition of ERK1/2 activation by PD98059 suppressed CTGF-mediated HS fi-broblasts proliferation significantly, while OD significantly dropped. Conclusion CTGF induces a prolif-erative response in HS fibroblasts, and this action is mainly dependent on the activation of ERK1/2 signal pathway.     

结缔组织生长因子影响体外培养瘢痕成纤维细胞ERK/MAPK信号通路活化及增殖的研究

Objective To explore the signal mechanism of proliferation stimulating effect of connec-tive tissue growth factor (CTGF) on hypertrophic scar (HS) derived fibroblasts. Methods <'3>H-TdR in-corporation technique was used to determine the proliferative effect of CTGF at different concentration. Western blot was applied to semi-quantitively analyze the expression of phosphorylated and total ERK1/2 protein after 0, 5, 10, 15, 30, and 60 min of CTGF stimulation, and the relative value of which was de-fined as AI to measure the activation of ERK1/2 signal pathway. PD98059 was admitted to specifically block the ERK1/2 pathway, and subsequently cell proliferation stimulated by CTGF was studied by MTT. Results CTGF could stimulate fibroblasts proliferation with a dose-dependant manner, and activa-ted the ERK1/2 signal pathway, and AI built up to 0.209±0.0201, reaching the apex at 15 min after stimulation performed. Inhibition of ERK1/2 activation by PD98059 suppressed CTGF-mediated HS fi-broblasts proliferation significantly, while OD significantly dropped. Conclusion CTGF induces a prolif-erative response in HS fibroblasts, and this action is mainly dependent on the activation of ERK1/2 signal pathway.     

结缔组织生长因子影响体外培养瘢痕成纤维细胞ERK/MAPK信号通路活化及增殖的研究

Objective To explore the signal mechanism of proliferation stimulating effect of connec-tive tissue growth factor (CTGF) on hypertrophic scar (HS) derived fibroblasts. Methods <'3>H-TdR in-corporation technique was used to determine the proliferative effect of CTGF at different concentration. Western blot was applied to semi-quantitively analyze the expression of phosphorylated and total ERK1/2 protein after 0, 5, 10, 15, 30, and 60 min of CTGF stimulation, and the relative value of which was de-fined as AI to measure the activation of ERK1/2 signal pathway. PD98059 was admitted to specifically block the ERK1/2 pathway, and subsequently cell proliferation stimulated by CTGF was studied by MTT. Results CTGF could stimulate fibroblasts proliferation with a dose-dependant manner, and activa-ted the ERK1/2 signal pathway, and AI built up to 0.209±0.0201, reaching the apex at 15 min after stimulation performed. Inhibition of ERK1/2 activation by PD98059 suppressed CTGF-mediated HS fi-broblasts proliferation significantly, while OD significantly dropped. Conclusion CTGF induces a prolif-erative response in HS fibroblasts, and this action is mainly dependent on the activation of ERK1/2 signal pathway.     

结缔组织生长因子影响体外培养瘢痕成纤维细胞ERK/MAPK信号通路活化及增殖的研究

Objective To explore the signal mechanism of proliferation stimulating effect of connec-tive tissue growth factor (CTGF) on hypertrophic scar (HS) derived fibroblasts. Methods <'3>H-TdR in-corporation technique was used to determine the proliferative effect of CTGF at different concentration. Western blot was applied to semi-quantitively analyze the expression of phosphorylated and total ERK1/2 protein after 0, 5, 10, 15, 30, and 60 min of CTGF stimulation, and the relative value of which was de-fined as AI to measure the activation of ERK1/2 signal pathway. PD98059 was admitted to specifically block the ERK1/2 pathway, and subsequently cell proliferation stimulated by CTGF was studied by MTT. Results CTGF could stimulate fibroblasts proliferation with a dose-dependant manner, and activa-ted the ERK1/2 signal pathway, and AI built up to 0.209±0.0201, reaching the apex at 15 min after stimulation performed. Inhibition of ERK1/2 activation by PD98059 suppressed CTGF-mediated HS fi-broblasts proliferation significantly, while OD significantly dropped. Conclusion CTGF induces a prolif-erative response in HS fibroblasts, and this action is mainly dependent on the activation of ERK1/2 signal pathway.