EGFR在TGFβ1诱导Ⅱ型肺泡上皮细胞转分化中的作用

目的探讨表皮生长因子受体(EGFR)在转分化因子β1(TGFβ1)体外诱导Ⅱ型肺泡上皮细胞转分化中的作用。方法体外培养Ⅱ型肺泡上皮细胞系细胞-A549细胞,以TGFβ1刺激,倒置相差显微镜观察细胞形态学的变化;收集不同时段的细胞,应用RT-PCR检测TGFβ1干预前后E-钙黏蛋白(E-cadherin)和α平滑肌肌动蛋白(α-SMA)mRNA表达变化;Western blot观察E-cad、α-SMA和信号转导蛋白EGFR表达的变化。结果倒置相差显微镜观察到TGFβ1刺激后A549细胞由鹅卵石状变为梭形,形态如同肌成纤维细胞;TGFβ1刺激A549细胞能导致E-cadherin mRNA和蛋白表达下调;α-SMA mRNA和蛋白表达上调;磷酸化EGFR(p-EGFR)表达上调。结论 TGFβ1能在体外诱导肺泡上皮细胞向间质细胞转分化,其机制与EGFR信号通路的活化相关。抑制EGFR的活化可能为临床防治肺纤维化提供新的途径。     

马兜铃酸I诱导人肾小管上皮细胞转分化的作用及机制

目的：探讨马兜铃酸Ｉ（Ａｒｉｓｔｏｌｏｃｈｉｓ ａｃｉｄ Ｉ,ＡＡＩ）在人类肾小管上皮细胞（ＨＫＣ）转分化中的可能作用,了解ＡＡＩ引起肾小管间质损害的机制。方法：将体外培养ＨＫＣ细胞分为无血清对照组（Ｃ组）和ＡＡＩ实验组两组,波形蛋白和α－平滑肌肌动蛋白（α－ｓｍｏｏｔｈ ｍｕｓｃｌｅ ａｃｔｉｎ,α－ＳＭＡ）表达的变化;应用流式细胞技术检测表达α－ＳＭＡ阳性（＋）的ＨＫＣ细胞百分率;采用免疫酶标     

Smad锚着蛋白在高糖诱导人肾小管上皮细胞细胞外基质沉积中的作用

目的:阐明Smad锚着蛋白(Smad anchor for receptor activation,SARA)在高葡萄糖诱导的人近端肾小管上皮细胞系(HK-2细胞)细胞外基质(ECM)沉积中的作用及分子机制,探讨以SARA为靶点抑制高葡萄糖诱导的HK-2细胞ECM沉积的策略.方法:用高浓度葡萄糖(30 mmol/L D-葡萄糖)刺激HK-2细胞,通过Western Blot及实时定量PCR( Real-time PCR)检测纤维连接蛋白(FN)和I型胶原(Col I),进而检测转化生长因子β1( TGF-β1)、Smad2、Smad3、p-Smad2、p-Smad3的表达变化,通过细胞免疫荧光、Western Blot、Real-time PCR检测SARA的表达变化;分别转染全长SARA质粒[SARA(WT)]及敲除SBD结构域的SARA质粒[SARA(dSRD)],检测转染后高糖诱导HK-2细胞FN及Col I表达的变化.结果:Western Blot及Real-time PCR结果显示,30mmol/L D-葡萄糖刺激后,HK-2细胞Col I蛋白及mRNA表达呈时间依赖性升高.高糖可诱导TGF-β1、Smad3蛋白及其mRNA表达呈时间依赖性上调;Smad2 mRNA表达呈时间依赖性上调,而其蛋白表达呈时间依赖性下调;高糖可促进Smad2和Smad3磷酸化,但Smad3的活化时间更长.而SARA的蛋白及mRNA表达呈时间依赖性降低,细胞免疫荧光结果亦证实高糖刺激后SARA表达下降.与高糖组相比,转染SARA(WT)可使HK-2细胞FN和 Col I表达下调;转染SARA (dSBD)对高糖诱导的HK-2细胞FN和ColI表达无明显影响.结论:高糖诱导的HK-2细胞ECM沉积过程中,TGF-β1信号通路活化,SARA的表达下调;过表达SARA可能通过上调Smad2的蛋白表达,抑制TGF-β31信号传导,从而减少高糖诱导的HK-2细胞ECM分泌.     

三七总皂甙对马兜铃酸Ⅰ诱导人肾小管上皮细胞转分化的作用及机制

目的 探讨三七总皂甙(PNS)治疗肾间质纤维化的作用机制.方法 将人肾小管上皮细胞(HK-2)按不同处理因素分为6组,空白对照组不予干预;PNS对照组加入PNS,使终质量浓度为 400 μg/ml;马兜铃酸I(AA I)诱导组加入AA I,终质量浓度为20 μg/ml;PNS低、中、高剂量组均加入AA I 20 μg/ml,同时分别加PNS 200、400、600 μg/ml.培养48 h后应用倒置相差显微镜观察细胞形态学变化;免疫组织化学法检测α-平滑肌肌动蛋白(α-SMA)表达;ELISA法测定细胞上清液中TGF-β1水平;RT-PCR法检测结缔组织生长因子(CTGF) mRNA表达.结果 AA I诱导组HK-2细胞从原来典型的上皮细胞形态转变为长梭形肌成纤维细胞形态,胞质内大量表达α-SMA,其积分光密度值、TGF-β1水平、CTGF mRNA表达均增加(P＜0.05);PNS各剂量组细胞形态学改变减轻,α-SMA、CTGF mRNA表达和TGF-β1分泌降低,且呈剂量依赖性(P＜0.05);PNS对照组各指标均无明显变化.结论 PNS可抑制AA I诱导的肾小管上皮细胞转分化作用,其机制可能是抑制TGF-β1及其下游因子CTGF表达.     

高糖诱导大鼠血管平滑肌细胞转分化的作用

目的:观察高糖对体外培养的大鼠胸主动脉血管平滑肌细胞(vascular smooth muscle cells, VSMCs)功能以及与成骨细胞转分化相关蛋白表达的变化,探讨糖尿病血管病变的可能细胞/分子发病机制. 方法:用组织贴块法建立SD大鼠胸主动脉VSMCs的体外培养技术;高糖(葡萄糖浓度:50 mmol/L)作用该细胞,设相同浓度甘露醇为对照组,观察在不同的培养时间下(3、12h和第3、6、9、12d),采用免疫蛋白印迹法和间接免疫荧光法分别检测α平滑肌肌动蛋白(α-SMA),骨桥蛋白(osteopontin,OPN)和成骨细胞特异性核转录因子(core-binging factor α-1,Cbfα-1/RUNX2)的表达.细胞钙沉积含量测定观察培养细胞钙盐的沉积. 结果:组织贴块法培养的大鼠原代胸主动脉VSMCs呈梭型,α-SMA表达强阳性;高糖作用12h,VSMCs的Cbfα-1表达明显上升;高糖作用9d后,VSMCs的α-SMA表达量较高糖作用前降低近90%;免疫荧光染色显示VSMC细胞呈低强度的α-SMA染色阳性;同时,高糖作用下的VSMCs能够检测到OPN蛋白的表达,与对照组相比差异显著;高糖作用下细胞钙沉积含量明显增加. 结论:持续的高糖作用能够使动脉VSMCs发生向类似成骨样细胞的转分化,提示高糖诱导的VSMCs转分化可能参与糖尿病血管病变的发生发展.     

Smad信号传递途径调节肾小管上皮细胞转分化实验

目的：研究转化生长因子β1(TGF—β1)诱导人肾小管上皮细胞(HKC)转分化作用与其细胞内信号传递途径的关系。方法：以细胞间粘连蛋白(E-cadherin)和α-平滑肌肌动蛋白(α-SMA)作为肾小管上皮细胞转分化的观察指标，借助细胞培养、蛋白印迹和基因转染等方法，检测TGF—β1引发的Smad信号途径的变化，和TGF—β1诱导的肾小管上皮细胞转分化作用。将含有Smad7基因表达质粒转染HKC细胞，观察高表达的Smad7蛋白对TGF—β1作用的影响。结果：实验结果表明①TGF—β1作用HKC细胞10min即可磷酸化HKC细胞内Smad2／3蛋白，而且此作用可持续48h以上；②TGF—β1作用HKC细胞6h即可下调E—cadherin蛋白的表达，24h后能诱导该细胞表达α-SMA，其作用呈明显的剂量依赖关系；③转染Smad7表达质粒的HKC细胞，可拮抗TGF—β1诱导HKC细胞表达α-SMA以及下调E—cadherin蛋白表达的作用；④应用特异性MAP激酶抑制剂(PD98059和SC68376)和PI3激酶抑制剂(Wortmannin)均不能拮抗TGF—β1的作用。结论：TGF—β1诱导的上皮细胞转分化作用是依赖其引发的Smad信号途径，阻断该信号传递途径则能够拮抗TGF—β1的作用。     

高糖通过转化生长因子依赖途径介导肾小管上皮细胞-肌纤维母细胞转分化及Ⅰ型胶原合成的机制

目的探讨高糖介导肾小管上皮细胞转分化及Ⅰ型胶原（Collagen Ⅰ）合成的分子机制。方法含35mmol／L葡萄糖培养液培养大鼠肾小管上皮细胞（NRK52E细胞）,免疫化学方法检测p-Smad2／3核转位,ELISA检测细胞培养上清中TGF-β1浓度,RT-PCR和Western blot方法分别检测α-SMA、E-eadherin、Collagen Ⅰ mRNA和蛋白的表达。观察TGF-β1中和抗体对高糖上述效应的影响。结果高糖促进NRK52E细胞合成和分泌TGF-β1。TGF-β1中和抗体能抑制高糖介导的p-Smad2／3核转位,下调高糖介导的α-SMA和Collagen Ⅰ蛋白表达,上调E-Cadherin蛋白表达（P均〈0．01）。结论高糖介导的肾小管上皮细胞转分化和细胞外基质Collagen Ⅰ的合成依赖于TGF-β1效应。     

内皮素-1诱导大鼠肾小管上皮细胞转分化的可能机制

目的:探讨内皮素-1(ET-1)是否可诱导大鼠肾小管上皮细胞转分化(TEMT)及可能的分子机制.方法:体外培养大鼠肾小管上皮细胞(NRK52E)并进行分组;倒置显微镜观察细胞的形态变化;Western印迹法检测细胞E钙黏蛋白(E-cadherin)、α平滑肌肌动蛋白(α-SMA)、p38丝裂原活化蛋白激酶(p38MAPK)及磷酸化-p38MAPK(p-p38MAPK)蛋白的表达;逆转录-聚合酶链反应(RT-PCR)法检测细胞E-cadherin及α-SMA mRNA的表达. 结果:ET-1可诱导细胞由鹅卵石样变为梭形,下调E-cadherin表达,上调α-SMA、p38 MAPK及p-p38MAPK表达,增强p38MAPK活性(P＜0.05),而内皮素A受体拮抗剂BQ123能明显抑制这些变化(P＜0.05).p38MAPK特异性抑制剂SB203580可抑制ET-1诱导的细胞梭形性变,ET-1诱导的E-cadherin、α-SMA及p-p38MAPK表达改变及p38MAPK活性改变(P＜0.05),但对p38MAPK表达无明显影响(P＞0.05). 结论:ET-1可能通过激活肾小管上皮细胞p38 MAPK通路,下调E-cadherin的表达,同时上调d-SMA的表达,从而诱导肾小管上皮细胞转分化.     

PI3K／Akt信号途径参与高糖诱导的肾小管上皮细胞转分化及对分化抑制因子2表达的影响

目的观察PI3K／Akt在高糖诱导的肾小管上皮细胞转分化中的作用及对分化抑制因子2（1d2）表达的影响。方法大鼠肾小管上皮细胞随机分成3组：对照（Con）组,高糖（H—Glu）组和PI3K抑制剂Wortmannin（Wort）组。Con组加正常培养液,限GIu组在培养液中加30mmol／L葡萄糖,Wort组用Wortmannin预处理1h后,加30mmol／L葡萄糖。24h后用免疫细胞化学、Western blot法和RT-PCR法检测α平滑肌肌动蛋白（α-SMA）、p-Akt和Id2的表达。结果Con组α-SMA、p-Akt阳性表达细胞很少,绝大部分细胞出现Id2阳性表达。与COn组比较,H-Glu组出现α-SMA和p-Akt表达升高,Id2表达降低（P〈0．05）。与H-Glu组比较,Wort组α-SMA和p-Akt表达下降,Id2表达升高（P〈0．05）。结论PI3K／Akt可能通过抑制Id2基因表达,参与高糖诱导的大鼠肾小管上皮细胞转分化。     

肾小管上皮细胞转分化中整合素连接激酶表达及其与衰老的相关研究

目的探讨整合素连接激酶(integrin-linked kinase,ILK)在肾小管上皮细胞转分化过程中的作用及其对衰老进程中细胞外基质(extracellular matrix,ECM)积聚增加的影响。方法分离培养3、24月龄 Wistar 雄性大鼠的原代肾小管上皮细胞,分别给予0、5、10、20～40μg/L 不同浓度的转化生长因子β(transforming growth factor β,TGF-β)刺激24h 后,用免疫细胞化学或免疫荧光方法检测细胞α-SMA、ILK、F-actin 表达;Western-blot 法检测两组细胞中纤维连接蛋白和 ILK 的表达水平;体外转录获得大鼠 ILK-c RNA 探针,检测两组细胞经刺激后 ILK mRNA 的变化。结果在0浓度 TGF-β刺激下,肾小管上皮细胞中 ILK 和 F-actin 表达水平24月龄组均比3月龄组高,但两组细胞α-SMA 表达水平均很低,且没有差别;随 TGF-β刺激浓度的增加,ILK、F-actin 和α-SMA 表达水平显著上调,其中 F-actin 与 ILK 表达增多相一致;FN 和 ILK 蛋白表达水平24月龄组分别为0.438±0.024和0.826±0.051,明显高于3月龄组的0.246±0.018和0.673±0.035(P<0.05)。结论随着肾小管上皮细胞转分化程度不断增高,ILK 表达增多,并可能通过调节 F-actin 的重排介导了转分化的过程;随增龄肾小管上皮细胞中 ILK 和 FN 表达增多,且 F-actin 表达随之增多,提示衰老肾脏的肾小管上皮细胞在应激状态下更易于发生转分化。     

AEG-1 participates in high glucose-induced activation of Rho kinase and epithelial-mesenchymal transition in proximal tubular epithelial cells

Objective:To prove whether astrocyte elevated gene-1(AEG-1) plays a role in high glucosestimulated Rho kinase activation and epithelial-mesenchymal transition(EMT) in human renal tubular epithelial(HK-2) cells.Methods:The protein levels of AEG-1,alpha-smooth muscle actin,E-cadherin and MYPT1 were determined by Western blot.Results:AEG-1 protein level was upregulated in HK-2 cells stimulated with high glucose.AEG-1 siRNA downregulated Rho kinase protein expression and blocked high glucose-induced EMT.Conclusions:Our results show that AEG-1 acts a key role in high glucoseinduced activation of Rho kinase and EMT in HK-2 cells.     

他克莫司对转化生长因子-β诱导的肾小管上皮细胞转分化的抑制作用及对核因子-κB活性的影响

目的:探讨他克莫司(FK506)对转化生长因子-β(TGF-β)诱导的肾小管上皮细胞转分化的作用,及其与核因子-κB(NF-κB)活性变化的关系.方法:以人类肾脏近曲小管上皮细胞株(Human kidney cell,HKC)为研究对象,分为以下4组:①阴性对照组;②TGF-β(8 ng/ml)组:③FK506(0.1、1、10、50 ng/ml)组:④TGF-β(8 ng/ml) FK506(0.1、1、10、50 ng/ml)组.应用形态学、间接免疫荧光法,免疫组化技术和酶联免疫吸附法观察FK506对TGF-β诱导的HKC细胞转分化的作用、细胞培养上清液纤连蛋白、Ⅰ型胶原的变化及FK506对HKC细胞NF-κB活性的影响.结果:FK506(1,10,50 ng/ml) TGF-β组比TGF-β组诱导的HKC细胞E-钙粘蛋白和细胞角蛋白表达有所增强,波形蛋白和α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)的表达比TGF-β组减弱(P＜0.05),同时HKC细胞NF-κB的活性比TGF-β组减弱(P＜0.05),培养上清液纤连蛋白及Ⅰ型胶原的浓度比TGF-β组降低(P＜0.05);FK506(1、10、50 ng/ml)使基础状态下HKC细胞NF-κB的活性明显下降(P＜0.05)和上清液中纤连蛋白及Ⅰ型胶原的水平明显降低(P＜0.05).结论:①FK506剂量依赖性地抑制TGF-β诱导的肾小管上皮细胞转分化和纤连蛋白及Ⅰ型胶原的形成及基础状态下和TGF-β诱导的HKC细胞NF-κB的表达.②FK506抑制TGF-β诱导的HKC细胞转分化很可能与NF-κB的表达下调有关,需要进一步研究.     

Insulin-like growth factor-binding protein-3 mediates high glucose-induced apoptosis by increasing oxidative stress in proximal tubular epithelial cells

IGF-binding protein-3 (IGFBP-3) is the major circulating carrier protein for IGF, and also acts as a potent antiproliferative agent in various cell types. Recently, IGFBP-3 was reported to mediate high glucose-induced apoptosis in mesangial cells and podocytes. In this study, we investigated the role of IGFBP-3 in high glucose-induced apoptosis in proximal tubular epithelial cells (PTEC). Expression of IGFBP-3 protein and mRNA in a porcine PTEC line (LLC-PK1 cells) was measured after exposure to either standard (5.5 mM) or high-glucose (30 mM) medium. We quantified apoptosis after treatment with small interfering RNA against IGFBP-3 (siRNA:IGFBP-3) in high-glucose medium or in cells that overexpressed IGFBP-3. Oxidative stress was measured in high-glucose medium, in the presence of siRNA:IGFBP-3, or in IGFBP-3-overexpressing cells. IGFBP-3 protein and mRNA expression in LLC-PK1 cells was higher in high-glucose medium than in standard-glucose medium. Exposure to high-glucose medium increased apoptosis, and high-glucose-induced apoptosis was abolished by siRNA:IGFBP-3. IGFBP-3 overexpression induced apoptosis in LLC-PK1 cells. Both high-glucose medium and IGFBP-3 overexpression increased reactive oxygen species, and siRNA:IGFBP-3 reduced this increase. Antioxidant treatment decreased IGFBP-3 expression and apoptosis, whereas oxidative stress from hydrogen peroxide increased IGFBP-3 expression, suggesting that oxidative stress increases IGFBP-3 expression. Our results suggest that increased IGFBP-3 expression by high glucose mediates high-glucose-induced apoptosis in PTEC. Increased oxidative stress from high glucose enhances IGFBP-3 expression, inducing apoptosis. Increased expression of IGFBP-3 by high glucose induces additional oxidative stress, which may result in amplification of hyperglycemic damage.     

Janus激酶2/信号转导和转录激活子3信号通路在心肌细胞缺氧损伤中的作用

目的探讨Janus激酶2/信号转导和转录激活子3(JAK2/STAT3)信号通路在心肌细胞缺氧损伤中的作用。方法体外培养的新生大鼠心肌细胞,构建缺氧模型,按随机数字表法分为正常对照组、缺氧组、JAK2抑制剂AG490处理组和STAT3抑制剂Statti c处理组。采用细胞计数试剂盒CCK-8检测心肌细胞活力,采用比色法检测细胞上清液中的乳酸脱氢酶(LDH)、丙二醛(MDA)、超氧化物歧化酶(SOD)含量,并采用缺口末端标记法(TUNEL)检测各组细胞的凋亡率。采用蛋白质印迹(Western blot)检测JAK2及STAT3蛋白表达及磷酸化情况。结果与正常对照组相比,缺氧组心肌细胞成活率明显降低,为对照组的30.14%±6.23%(P<0.01),细胞上清液中LDH、MDA含量升高明显,分别为(50.11±2.58)U/L和(19.55±1.81)mol/L(均为P<0.01),SOD活力则显著降低,为(10.21±0.57)U/ml(P<0.01),缺氧组凋亡率明显升高,为24.24%±4.37%(P<0.01),JAK2、STAT3磷酸化水平上调。AG490及Stattic预处理后,JAK2及STAT3磷酸化水平降低,心肌细胞成活率明显升高(P<0.01),LDH、MDA含量显著低于缺氧组(均为P<0.01),SOD活力则高于缺氧组(P<0.01)。结论 JAK2/STAT3信号通路参与了缺氧所致心肌细胞损伤,抑制JAK/STAT通路有助于减轻缺氧所致心肌损伤。     

JAK/STAT 信号通路在肺纤维化中作用的研究进展

蛋白酪氨酸激酶(JAK)/信号转导转录激活因子(STAT)信号通路是介导炎症反应的重要信号通路之一,广泛参与细胞的增生、分化、凋亡、免疫调节等病理生理过程。JAK/STAT 信号通路通过介导肺巨噬细胞、成纤维细胞、肺泡上皮细胞的病理性活化及损伤,对肺纤维化进程具有重要调控作用。此文就 JAK/STAT 信号通路在肺纤维化中的作用机制及研究进展作一综述。     

Potent activation of multiple signalling pathways by C-peptide in opossum kidney proximal tubular cells

Aims/hypothesis Proinsulin C-peptide is generally believed to be inert without any appreciable biological functions. However, it has been shown to modulate a variety of cellular processes important in the pathophysiology of diabetic complications. We therefore investigated the ability of C-peptide to stimulate intracellular signalling pathways in kidney proximal tubular cells, the altered activation of which may possibly be related to the development of diabetic nephropathy.Methods Extracellular signal-regulated kinase (ERK) and Akt phosphorylation were evaluated by western blotting. ERK activity was measured by in vitro kinase assay. Intracellular Ca²⁺ was evaluated by confocal imaging. The membrane and cytosol-associated fractions of protein kinase C (PKC) isoforms were evaluated by western blotting. Proliferation was assessed by thymidine incorporation assay.Results Using the opossum proximal tubular kidney cell line as a model, we demonstrated that at high picomolar to low nanomolar concentrations, C-peptide stimulates extracellular signal-regulated mitogen-activated kinase (3.3±0.1-fold over basal at 3 minutes) and phosphatidylinositol 3-kinase (4.1±0.05-fold over basal at 5 minutes). ERK activation was attenuated by pre-treatment with a PKC inhibitor and abolished by pertussis toxin. Elevations of intracellular [Ca²⁺] are seen in response to 5 nmol/l C-peptide with consequent activation of PKC-. Pre-treatment with pertussis toxin abolished PKC-. C-peptide is also a functional mitogen in this cell type, stimulating significantly increased cell proliferation. Proliferation was attenuated by wortmannin and pertussis toxin pre-treatments. None of these effects is reproduced by scrambled C-peptide.Conclusions/interpretation This study provides evidence that C-peptide, within physiological concentration ranges, stimulates many signalling pathways in opossum kidney cells.Abbreviations Akt/PKB protein kinase B - DTT dithiothreitol - ERK extracellular signal-regulated kinase - GPCR G-protein coupled receptor - MAPK mitogen-activated protein kinase - OK opossum kidney - PI3-K phosphoinositide 3-kinase - PKC protein kinase C - PMA phorbol myristate acetate - PMSF phenylmethansulfonylfluoride - PTC proximal tubular cells - PTX pertussis toxin     

Endocytosis provides a major alternative pathway for lysosomal biogenesis in kidney proximal tubular cells

Recruitment of acid hydrolases to lysosomes generally occurs by intracellular sorting based on recognition of a common mannose 6-phosphate signal in the transGolgi network and selective transport to late endosomes/lysosomes. Here we provide evidence for an alternative, efficient secretion-recapture pathway mediated by megalin and exemplified by cathepsin B in kidney proximal convoluted tubules (PCT). We found that in mouse kidneys with defective megalin expression [megalin knockout (KO)] or apical PCT trafficking (ClC-5 KO), the (pro)cathepsin B mRNA level was essentially preserved, but the protein content was greatly decreased and the enzyme was excreted in the urine as mannose 6-phosphate-devoid species. In polarized PCT-derived cells, purified cathepsin B was avidly and selectively taken up at the apical membrane, and uptake was abolished by the megalin competitor, receptor-associated protein. Direct interaction of cathepsin B with megalin was demonstrated by surface plasmon resonance. Procathepsin B was detected in normal mouse serum. Purified cathepsin B injected into mice was efficiently taken up by kidneys (approximately 10% of injection) and targeted to lysosomes where it remained active, as shown by autoradiography and subcellular fractionation. A single cathepsin B injection into cathepsin B KO mice could reconstitute full lysosomal enzyme activity in the kidneys. These findings demonstrate a pathway whereby circulating lysosomal enzymes are continuously filtered in glomeruli, reabsorbed by megalin-mediated endocytosis, and transferred into lysosomes to exert their function, providing a major source of enzymes to PCT. These results also extend the significance of megalin in PCT and have several physiopathological and clinical implications.     

CD40/CD40L在肾小管上皮细胞转分化中的作用及其可能机制

目的 探讨CD40/CD40L在肾小管上皮细胞转分化中的作用及其可能机制.方法 将74例IgA肾病患者肾穿活检组织分为轻度系膜增生组27例、局灶增生组28例和增生硬化组19例,采用免疫组化及Masson方法观察各组肾小管间质内CD40、CD40L、TGF-β、α-SMA、Vimentin和胶原纤维的表达.结果 IgA肾病组织中小管上皮细胞高表达CD40和CD40L,肾小管间质中TGF-β、α-SMA、Vimentin及胶原纤维表达随分级变化而变化,三组间以上指标比较有统计学差异（P＜0.05或＜0.01）.结论 IgA肾病中,CD40和CD40L可能通过TGF-β启动并调节肾小管上皮细胞转分化,参与肾小管间质纤维化.