高糖高溶血磷脂胆碱环境下血小板活化因子在内皮细胞与系膜细胞相互关系中的作用

目的 探讨高糖高溶血磷脂胆碱环境下内皮细胞与系膜细胞相互作用对细胞外基质(ECM)积聚的影响及血小板活化因子(PAF)在其中的作用.方法 人脐静脉内皮细胞(HUVEC)与人肾小球系膜细胞(HMC)共培养和HMC单独培养,将两种培养模型分别分为对照组、甘露醇组、高糖高脂组、PAF受体拮抗剂BN52021组,比较各组细胞上清液人纤维连接蛋白(Fn)、人Ⅳ型胶原(Col IV)、PAF含量及HMC中PAF受体(PAF-R)mRNA的表达水平.结果 (1)高糖高脂促进单培养和共培养细胞Fn、 Col IV和PAF含量的升高,且共培养组Fn、 Col IV和PAF水平均高于单培养组,BN52021可抑制高糖高脂刺激的Fn和Col IV升高(P均<0.05).(2)高糖高脂上调HMC中PAF-R mRNA的表达水平(P<0.05).结论 高糖高脂环境下,系膜细胞和内皮细胞存在异常的相互作用,促进Fn、Col IV、PAF的产生,高糖高脂刺激的ECM分泌增加可能与PAF有关.     

内皮素-1、NF-κB及AP-1对高糖诱导大鼠肾小球系膜细胞纤维连接蛋白表达的影响

目的探讨高糖（HG）对大鼠肾小球系膜细胞（GMC）表达纤维连接蛋白（FN）的影响及内皮素-1（ET-1）、NF-κB和AP-1在FN表达中的作用。方法建立高糖培养条件下的大鼠肾小球系膜细胞模型,在mRNA水平及蛋白水平检测不同条件下的ET-1和FN表达。结果（1）HG组与正常糖浓度（NG）组比较,HG组ET-1及FN的mRNA和蛋白表达显著增加（P〈0.01）。（2）NG组加入ET-1（5nmol/L）后,FNmRNA及蛋白表达增加（P〈0.01）,加入ET-1受体拮抗剂PD142893（10μmol/L）后,HG及ET-1诱导的FNmRNA及蛋白表达均被明显抑制（P〈0.01）。（3）给予NF-κB抑制剂PDTC（10μmol/L）后,HG及ET-1诱导的FNmRNA及蛋白表达均被明显抑制（P〈0.01）。（4）给予JNK特异性抑制剂SP600125（10μmol/L）后,HG及ET-1诱导的FNmRNA及蛋白表达均被明显抑制（P〈0.01）。结论HG增强大鼠GMC表达FN的作用通过ET-1介导,NF-κB和AP-1参与调控ET-1介导的FN表达增加。     

高血压病患者血浆内皮素-1浓度的变化及氯沙坦干预的效果

目的:探讨内皮素—1在EH发生中的作用以及氯沙坦干预前、后EH患者内皮素—1水平的变化。方法:76例高血压患者眼用氯沙坦6周(剂量50～100mg/d),部分患者加用双氢氯噻嗪(12.5mg,2次/d),观察氯沙坦治疗前、后血压和血浆内皮素—1的变化。结果:EH组与对照组血浆内皮素—1水平分别为89.13±29.17ng/L、60.13±10.23ng/L,前者显著升高(P<0.05),高血压Ⅲ级者的ET-1水平显著高于高血压Ⅱ级的(P<0.05)。氯沙坦治疗前、后内皮素—1水平分别为89.13±29.17ng/L、65.32±7.19ng/L,治疗后的显著降低(P<0.01)。氯沙坦治疗前收缩压和舒张庄分别为168.34±12.92、112.46±6.09mmHg,治疗后分别为125.71±20.05、80.15±5.11mmHg,均较治疗前明显降低(P<0.01)。结论:内皮素—1在高血压的形成和维持中起者重要的作用,氯沙坦在有效降压时,可以降低血浆内皮素—1水平。     

高糖状态下肾脏系膜细胞葡萄糖转运蛋白1的表达及氟伐他汀的干预研究

目的观察高糖环境中大鼠肾脏系膜细胞（MC）葡萄糖转运蛋白1（GluT-1）及转化生长因子1（TGF-β1）mRNA表达变化以及氟伐他汀（Flu）的干预作用，探讨其保护肾脏的可能机制。方法原代培养MC分为正常对照（NG）组、甘露醇（MG）组、高糖（HG）组及HG＋Flu组，RT-PCR法检测细胞中GluT-1mRNA和TGF-β1 mRNA的表达，放免法测定各组细胞培养上清液中Ⅳ型胶原含量。结果HG组各时相点GluT-1mRNA、TGF-β1 mRNA表达量均高于NC组（P〈0．01），从48h开始HG组细胞上清液Ⅳ型胶原的含量较NC组增高（P〈0．05），而HG＋Flu组GluT-1 mRNA表达量、TGF-β1 mRNA的表达、细胞上清液Ⅳ型胶原含量均较同时点HG组明显降低（P〈0．01）。结论高糖刺激使MC内GluT-1 mRNA表达增高，TGF-β1 mRNA表达上调，Ⅳ型胶原分泌增多。高糖状态下，Flu抑制细胞外基质积聚的作用可能与其抑制高糖引起MC GluT-1过表达、减少TGF-β1的合成有关。     

氯沙坦对糖尿病大鼠肾小管间质TGF-β1和α-SMA的影响

目的研究血管紧张素ⅡⅠ型受体拮抗剂(AT_1RA)——氯沙坦对链脲佐菌素(STZ)大鼠肾小管间质转化生长因子-β_1(TGF—β_1)和平滑肌肌动蛋白(α—SMA)表达的影响。方法用Wistar大鼠建立STZ诱导的糖尿病(DM)大鼠模型,设正常对照组(A),糖尿病组(B)和糖尿病 氯沙坦治疗组(C)。用免疫组化方法检测肾小管问质TGF—β_1和α—SMA蛋白的表达,RT—PCR检测TGF-β-1mRNA。结果TGF—β_1和α—SMA在DM大鼠肾小管间质的表达较正常对照组显著升高(P＜0．05),C组与同期B组相比明显降低(P＜0．05)。结论氯沙坦能降低糖尿病大鼠肾小管间质TGF—β_1和α—SMA的表达,缓解肾小管间质病理损害。     

氯沙坦对糖尿病肾病患者尿中转化生长因子β1的影响

目的 探讨2型糖尿病肾病患者尿转化生长因子(TGF)β1的状况及氯沙坦对抗纤维化的影响.方法 检测33例2型糖尿病肾病患者氯沙坦(50 mg/d×8周)治疗前后24小时尿蛋白、尿肌酐,尿TGFβ1和肌酐水平.尿TGFβ1的检测用ELISA法.20例健康志愿者的尿液标本作为对照组.结果 与对照组比较,患者尿TGFβ1明显升高,随肾小球滤过功能损害的加重,尿TGFβ1排出增加,治疗前、治疗后尿TGFβ1浓度明显下降(P＜0.001).尿TGFβ1浓度变化与尿蛋白变化具有相关性(P＜0.01).结论 随肾功能损害的加重,2型糖尿病肾病患者肾脏纤维化加重, 氯沙坦通过降低2型糖尿病肾病患者TGFβ1水平发挥抗肾脏纤维化作用,尿TGFβ1减少可能是病情缓解的早期表现,这一表现可先于蛋白尿的变化.     

心力衰竭患者肿瘤坏死因子、内皮素的变化及氯沙坦对其影响

目的 :探讨心力衰竭患者肿瘤坏死因子 (TNF)、内皮素 (ET- 1)的变化及氯沙坦对其影响。方法 :采用放免法检测 44例心力衰竭患者及 2 2例健康者血 ET- 1和 TNF- α浓度。将 44例心力衰竭患者随机分为两组 :A组 :入选 2 1例 ,给予常规抗心力衰竭治疗 ;B组 :入选 2 3例 ,在 A组治疗药物的基础上加氯沙坦 5 0 m g,每日 1次 ,共 1个月。结果 :1心力衰竭患者 ET- 1和 TNF- α水平显著高于对照组 (P <0 .0 5 )。 2两组患者治疗后心力衰竭均有明显改善 ,但以氯沙坦治疗后 ET- 1和 TNF-α水平下降显著 (P <0 .0 5 )。结论 :ET- 1,TNF-α与心力衰竭的发生发展有关 ,氯沙坦治疗可降低心力衰竭患者 ET- 1,TNF-α水平。     

高糖培养下大鼠肾小球系膜细胞JunD表达及转录因子-激活物蛋白1的活化

转录因子激活物蛋白 1(ａｃｔｉｖａｔｏｒｐｒｏｔｅｉｎ 1,ＡＰ 1)在糖尿病肾病特征性病理改变的发生发展中起重要作用。转化生长因子 (ＴＧＦ) β1、肾小球细胞外基质的重要成分层粘蛋白、Ⅰ型胶原的启动子区域都含有ＡＰ 1的结合位点 ;已有文献提示ＡＰ 1的活化介导了高糖诱导的ＴＧＦ β1表达升高〔1〕,同时ＡＰ 1也参与了ＴＧＦ β1诱导的细胞外基质表达升高〔2〕。转录因子ＡＰ 1由Ｊｕｎ蛋白 Ｆｏｓ蛋白异源二聚体或Ｊｕｎ蛋白同源二聚体组成。其二聚体 (ＪｕｎＤ)为其活化形式 ,可与ＴＰＡ反应元件结合 ,启动靶基因的转录。ＡＰ 1…     

氯沙坦对Thy1肾炎大鼠肾小球系膜细胞CDK2表达的影响

目的 观察氯沙坦对Thy1肾炎大鼠肾小球系膜细胞人细胞周期蛋白依赖性激酶2(CDK2)表达的影响.方法 实验鼠分为Thy1肾炎组、Thy1肾炎+氯沙坦治疗组和正常组.诱导肾脏疾病后,第1、3、5、7天检查病理.用免疫组化方法检测;肾小球内PCNA和CDK2蛋白的表达情况,采用Western印迹分析CDK2的表达情况.结果 对于正常大鼠,其系膜细胞的CDK2表达量很低,但具有系膜细胞增生现象的肾炎大鼠,CDK2表达会有增加趋势.比较而言,用氯沙坦治疗3～7d后,肾小球内的PCNA表达明显低于肾炎组(P＜0.05).结论 CDK2可导致肾小球系膜细胞增生,氯沙坦对系膜细胞CDK2的高表达有明显的抑制作用,进而抑制系膜细胞的增生,表明氯沙坦可以治疗Thy1肾炎大鼠系膜细胞增殖.     

氯沙坦对高血压患者血清一氧化氮、内皮素-1和血管内皮功能的影响

目的 探讨氯沙坦对高血压患者血清一氧化氮（NO）、内皮素-1（ET-1）和血管内皮功能的影响.方法 入选108例首诊轻、中度高血压患者,给予氯沙坦50～100 mg,qd,共12周;另人选同期健康体检者为正常对照组（对照组100例）.观察高血压患者治疗前后血流介导的肱动脉内皮依赖性血管舒张功能（FMD）、ET-1和NO的变化.结果 随访12周后,与治疗前比较,高血压患者的血压下降,FMD提高,NO上升,ET-1降低（均P〈0.05）.多元线性逐步回归显示,校正年龄、血压、血脂、血糖等因素后,ET-1和NO是FMD的影响因素（均P〈0.05）.结论 氯沙坦改善高血压患者血管内皮功能可能与减少内皮素分泌,增加一氧化氮水平有关.     

内皮素-1对人腹膜间皮细胞合成细胞外基质及转化生长因子β1的影响

目的:研究内皮素1(ET1)及非特异性内皮素受体拮抗剂即ETA/ETB拮抗剂PD142893对人腹膜间皮细胞(HPMC)分泌细胞外基质(ECM)及转化生长因子β1(TGFβ1)产生的影响。方法:以人腹膜间皮细胞株(HMrSV5)为研究对象,采用放免法、半定量逆转录多聚酶链反应(RTPCR)观察不同浓度的葡萄糖及PD142893对HPMCET1、Ⅳ型胶原(ColⅣ)、纤连蛋白(Fn)分泌和基因表达的影响,及TGFβ1蛋白水平(ELISA),基质金属蛋白酶2(MMP2)基因表达(RTPCR)。结果:①葡萄糖对ET1的影响:高浓度葡萄糖增加HPMCET1的分泌及基因表达,葡萄糖浓度为50、100、150mmol/LET1分泌分别为(2.57±0.18)、(2.82±0.89)、(4.12±0.83)pg/ml·105cell,呈剂量依赖。②ET1促进HPMC分泌ColⅣ,增强ColⅣ、MMP2mRNA的表达。PD142893可下调高糖诱导的ColⅣ、Fn和MMP2。③ET1刺激HPMC分泌TGFβ1呈剂量依赖,ET1浓度为0、10、50、100nmol/L时分泌TGFβ1分别为(2141.74±45.16)、(2181.6±95.13)、(4360.58±139.74)、(6966.88±444.93)pg/ml·105cell,PD142893可明显抑制高糖诱导TGFβ1的分泌。结论:ET1促进HPMC分泌ECM,高糖诱导间皮细胞ECM合成与ET1及TGFβ1途径有关。     

Effect of losartan on angiotensin II-mediated endothelin and prostanoid excretion in humans

Angiotensin II (Ang II) stimulates renal prostanoid and vascular endothelin-1 (ET-1) release. Most known Ang II effects are mediated by AT₁ receptors. Our aim was to determine whether AT₁ receptor activation mediates Ang II-evoked renal prostanoid and ET-1 release. Eleven healthy men were randomized in a crossover, double-blind fashion to receive 100 mg/day of losartan or matching placebo, for 8 days. Blood and urine were sampled before and after a 2-h infusion of Ang II at a rate previously determined to increase mean arterial pressure (MAP) by 25 to 30 mm Hg in each subject. After a 14-day washout, subjects received the alternate treatment. Pretreatment with losartan had little effect on baseline MAP, but increased plasma renin activity, and virtually eliminated the pressor response to Ang II infusion. Angiotensin II significantly increased prostanoid excretion after placebo; the prostanoid response to Ang II was even greater after losartan. Plasma ET-1 was not altered by Ang II infusion, with or without losartan. In contrast, urine ET-1 excretion rate decreased to 40% of baseline after Ang II but not after losartan pretreatment; losartan alone had no effect. We conclude that Ang II decreases renal ET-1 synthesis and release through the AT₁ receptor. In contrast, Angiotensin II-mediated renal prostanoid synthesis does not require activation of AT₁ receptors. These findings indicate that AT₁ receptor antagonists could provide renal protection through indirect mechanisms.     

氯沙坦抑制环孢素A诱导的系膜细胞增生和细胞外基质形成

目的：观察免疫抑制剂环孢素A(CsA)对系膜细胞(MC)增生及细胞外基质(ECM)分泌的影响以及氯沙坦的干预作用，初步探讨环孢素致肾小球硬化的机制。方法：体外培养大鼠肾小球MC，用氚标胸腺密暖核苦(^3H-TdR)掺入法测定CsA对MC增生的影响，用酶联免疫吸附实验(ELISA)测定细胞上清液中转化生长因子β1(TGF—β1)及ECM成份纤维连接蛋白(fibronectin,Fn)的分泌，用逆转录-聚合酶链反应(RT—PCR)方法测定TGF—β1、I型前胶原、基质金属蛋白酶2(MMP—2)的基因表达。结果：CsA对MC的增生有明显的抑制作用，并呈现时间和剂量依赖效应，氯沙坦对细胞的增生无明显作用；环孢素能明显促进TGF—β1及Fn的分泌，并能促进TGF—β1、I型前胶原mRNA的表达，下调MMP—2 mRNA的表达，氯沙坦能下调环孢素诱导的TGF—β1及Fn的表达。结论：环孢素影响MC增生和ECM分泌从而引起肾小球硬化，肾素—血管紧张素—醛固酮系统可能部分参与了这一过程。     

氯沙坦钾对慢性心力衰竭小鼠肾脏内皮素1表达的影响

目的探讨慢性心力衰竭(chronic heart failure,CHF)小鼠肾脏内皮素1(endothelin,ET-1)的表达,了解氯沙坦钾对CHF小鼠肾脏ET-1表达的影响。方法选择30只昆明小鼠随机分为3组:假手术组,CHF组,氯沙坦钾组,每组10只。光镜下观察HE染色后小鼠肾组织的病理改变;RT-PCR法检测小鼠肾脏组织ET-1 mRNA的表达;免疫组织化学和Western blot检测肾组织ET-1蛋白的表达。结果CHF组小鼠肾小管上皮细胞有明显空泡形成,氯沙坦钾组小鼠肾组织病理改变有所减轻。CHF组小鼠肾组织ET-1基因和蛋白表达水平显著高于假手术组;氯沙坦钾组小鼠治疗后ET-1基因及蛋白表达水平较CHF组高。结论CHF小鼠肾组织存在ET-1基因和蛋白表达增加,氯沙坦钾在保护肾脏的同时能增加其在肾脏的表达。     

Sickle erythrocytes increase prostacyclin and endothelin-1 production by cultured human endothelial cells under flow conditions

We investigated the effects of sickle erythrocytes on the production of vasotone mediators in endothelial cells (ECs) using an in vitro recirculating flow system. Sickle erythrocytes increased the EC production of two important vasoactivators, prostacyclin and endothelin-1, under venous wall shear stress conditions of 1dyncm2. The presence of interleukin-1 in the perfusion system, as a model for inflammatory cytokine effects, enhanced the overall amounts of released prostacyclin but did not affect the production of endothelin-1. This study demonstrates the effects of sickle erythrocytes on the function and metabolism of ECs under vascular flow environments. The altered production of vasoactivators may contribute to the vasotone instability and vasoocclusive crises in sickle cell anemia.     

氯沙坦对自发性2型糖尿病KKAy小鼠肾脏损害的保护作用

目的探讨氯沙坦在治疗KKAy小鼠糖尿病早期肾损害中的应用价值。方法将20只雄性8周龄KKAy小鼠随机分为治疗组（n=10）和非治疗组（n=10）,治疗组从8周龄始予以氯沙坦10 mg/（kg.d）饮水喂入,C57BL/6小鼠为正常对照组（n=10）。于20周龄测定各组小鼠血糖、尿微量白蛋白、尿肌酐,并留取肾脏标本,于光镜及电镜下观察其肾脏病理改变。结果氯沙坦治疗对KKAy小鼠体质量及血糖无影响;与非治疗组比较,氯沙坦治疗减少了KKAy小鼠的尿白蛋白/肌酐比率（P〈0.05）,改善了KKAy小鼠的病理损害。结论氯沙坦治疗能减少KKAy小鼠尿白蛋白排泄率,改善肾脏病理损害。     

Phytoestrogen alpha-zearalanol antagonizes oxidized LDL-induced inhibition of nitric oxide production and stimulation of endothelin-1 release in human umbilical vein endothelial cells

Oxidative modification of low-density lipoprotein (LDL) leads to formation of the atherogenic molecule oxidized LDL (oxLDL), which is considered to be an important mediator for vascular endothelial dysfunction and atherosclerosis. It is speculated that reduced nitric oxide (NO) release/bioavailability and enhanced release of endothelin-1 (ET-1) may contribute to oxLDL-induced endothelial dysfunction. Estrogen may improve lipid profile and inhibit oxLDL-induced endothelial damage. However, estrogen replacement therapy has been suspended due to uncertainty in benefits versus risk (such as cancer progression) in postmenopausal women. This study was designed to evaluate the effect of a novel phytoestrogen, α-zearalanol (α-ZAL), on oxLDL-induced effect on NO and ET-1 production in human umbilical vein endothelial cells (HUVEC). HUVEC were incubated with oxLDL (50 μg/mL) for 24 h in the absence or presence of α-ZAL (0–1000 nM), 17β-estradiol (E₂, 10 nM), or the E₂ receptor antagonist ICI 182780 (1 μM). Levels of NO and ET-1 were measured by spectrophotometry and enzymatic immunoassay, respectively. NOS activity was evaluated by conversion of ³H-arginine to ³H-citrulline. Protein and mRNA expression of NOS and ET-1 were measured by Western blot and RT-PCR. Our results indicated that oxLDL significantly reduced NO release and NOS activity, and enhanced ET-1 production associated with reduced NOS3 (but not NOS2) expression and enhanced ET-1 mRNA expression. All these oxLDL-induced alterations were significantly attenuated or abolished by co-incubation with α-ZAL or E₂, both through an E₂ receptor-dependent mechanism. α-ZAL, E₂, and ICI182780 had no effect on NO/ET-1 release, NOS activity, or expression of NOS and ET-1. These data suggested that the phytoestrogen α-ZAL, like E₂, may effectively antagonize oxLDL-induced decrease in NO and increase in ET-1, which may be protective for endothelial function.     

雌激素对高胆固醇兔一氧化氮及内皮素生成的影响

观察雌激素对去卵巢高胆固醇兔动物模型主动脉一氧化氮及血浆内皮素-1的影响,以阐明雌激素抗动脉粥样硬化的部分机理.将21只纯种新西兰雌兔随机分入3组(各7只):A组(去卵巢未补充激素兔),B组(去卵巢补充雌激素兔),C组(未切除卵巢兔),都给予1%胆固醇饮食,8周后取主动脉应用Greiss试剂测定不同浓度的乙酰胆碱作用下主动脉NO代谢物NO_2~-及血浆内皮素的量.10~(-5)乙酰胆碱作用下,B、C组主动脉NO_2~-产量明显低于A组P<0.05),B、C组兔主动脉反应性高,10~(-5)乙酰胆碱作用下NO_2~-产量明显高于同组无乙酰胆碱时NO_2~-产量,A组即使在10~(-5)乙酰胆碱作用下,NO_2~-无明显增高.A组内皮素明显高于B组(P<0.05)及C组(P<0.01).雌激素在整体水平促进NO产生,并抑制内皮素-1生成,可能为抑制动脉粥样硬化形成的重要机理.     

内皮素-1与肺缺血/再灌注损伤的实验研究

目的 :探讨内皮素 -1（ET-1）在肺缺血 /再灌注 （I/ R）损伤中的作用。方法 :健康新西兰大白兔 3 0只随机分成 3组 （每组 10只 ） :假手术组 （ 组 ）、I/ R+生理盐水 （ 组 ）和 I/ R+ ET-1抗体组 （ 组 ）。观察肺再灌注 0 ,60 ,12 0 ,2 40min各时间点肺动脉压 （PA）、动脉氧分压 （Pa O2 ）和血浆 ET-1的变化。实验结束时 ,检测支气管肺泡灌洗液（BAL F）中 ET-1和肺组织丙二醛 （MDA）的含量和肺组织光镜的变化。结果 : 组血浆和 BAL F的 ET-1水平、肺组织 MDA含量和 PA升高 ,Pa O2 降低。 组 PA和 Pa O2 没有明显变化 ,血浆和 BAL F的 ET-1水平、肺组织 MDA含量的升高得到抑制。结论 :ET-1参与肺缺血 /再灌注损伤 ,能改善 PA和 Pa O2 。     

High glucose and hyperosmolality stimulate hepatocyte growth factor secretion from cultured human mesangial cells

Summary Hepatocyte growth factor is a recently cloned potent mitogen to hepatocytes, but its extrahepatic roles are not completely defined. It causes proliferation of endothelial and epithelial cells implicating potential action in the glomerulus. We aimed to determine whether cultured human mesangial cells secrete hepatocyte growth factor and the effect of high glucose conditions. Mesangial cells were isolated from the normal cortex of a child's kidney. After differential glomerular sieving and trypsin digestion of glomeruli, mesangial cells were cultured in 20 % fetal calf serum/RPMI. Glucose concentration in the medium was adjusted to 5 mmol/l, 11 mmol/l, 25 mmol/l or 5 mmol/l/20 mmol/l mannitol to correct for osmolality. After 0, 24, 48, 72 h incubation, hepatocyte growth factor was measured in the supernatant by enzyme immuno assay using recombinant hepatocyte growth factor and monoclonal antibodies to human hepatocyte growth factor. Hepatocyte growth factor was secreted by cultured mesangial cells. High glucose and hyperosmolar conditions caused a 100–200 % increase in hepatocyte growth factor secretion at 48–72 h (p =0.001). Hepatocyte growth factor secretion at 48 h in 5 mmol/l glucose was 16.46±1.09 ng/ml (mean ± SEM), 11 mmol/l glucose: 32.98±4.54, 25 mmol/l glucose: 33.32±7.89, 5 mmol/l glucose/20 mmol/l mannitol: 34.05±3.64; at 72 h in 5 mmol/l glucose: 23.92±2.85 ng/ml, 11 mmol/l glucose: 28.26±2.03, 25 mmo/l glucose: 62.04±12.2, 5 mmol/l glucose/20 mmol/l mannitol: 45.76±6.25. Trypan blue exclusion demonstrated membrane integrity. These findings demonstrate for the first time that cultured human mesangial cells secrete hepatocyte growth factor and there is stimulation by high glucose and hyperosmolar conditions. Hepatocyte growth factor may have a renotropic role in the pathogenesis of diabetic nephropathy. [Diabetologia (1994) 37: 533–535] Received: 11 November 1993 and in revised form: 13 December 1993