黄芪多糖与Ⅰ型胶原协同促血管新生的细胞学研究

目的观察黄芪多糖载入Ⅰ型胶原促血管新生作用,探讨黄芪多糖与Ⅰ型胶原的协同作用。方法通过人脐静脉血管内皮细胞（HUVEC）增殖实验测定不同浓度黄芪多糖和胶原对细胞的增殖作用,并测量细胞迁移率;Western Blot方法验证血管生成素-1（Ang-1）、整合素蛋白αvβ3、血管内皮生长因子（VEGF）的表达。结果黄芪多糖浓度20μg/mL时促进HU-VEC生长作用最明显,此后随着浓度的升高,促生长的作用逐渐降低,但均显著高于对照组（P〈0.01）;而黄芪和胶原合用,对细胞的促生长有协同作用,显著高于20μg/mL胶原组（P〈0.05）。20μg/mL黄芪多糖＋20μg/mL胶原时HUVEC迁移能力最强;Western Blot结果提示Ang-1、VEGF和integrinαvβ3的表达随着黄芪和胶原浓度的增加而升高;20μg/mL黄芪多糖＋胶原组达到最高。结论黄芪多糖能促进HUVEC的增殖和迁移,并上调Ang-1、VEGF和Integrinαvβ3的表达,具有促进血管新生的作用,且黄芪多糖和胶原具有协同作用。     

小牛血清和血小板源性生长因子对肺动脉平滑肌细胞Na^＋／H^＋交换器活性和细胞增殖的影响

目的：探讨小牛血清和血小板源性生长因子（PDGF）对大鼠肺动脉平滑肌细胞Na^ /H^ 交换器－1（NHE－1）表达和活性的影响，及其与细胞增殖的关系。方法：体外培养肺动脉平滑肌细胞，10％小牛血清、PDGF－BB作用24小时后检测细胞NHE－1mRNA表达、^22Na摄取量、细胞内pH(pHi)和^3H-TdR掺入量，观察不同浓度NHE－1抑制剂－乙基，异丙基氨氯吡咪（EIPA）对细胞凋亡率的影响。结果：10％小牛血清、PDGF作用后24小时，肺动脉平滑肌细胞中NHE－1mRNA表达、^22Na摄取量明显增加，同时伴有pHi增高和^3H-TdR掺入量增加，以10％小牛血清作用更为显著。随着EIPA浓度增加和作用时间延长，细胞凋亡率明显增高。结论：小牛血清、PDGF等生长因子参与调节肺动脉平滑肌细胞NHE－1表达和激活，使细胞内碱化，可能在细胞增殖中起重要作用。     

血管内皮生长因子、血管生成素与缺血性脑损伤

在啮齿动物的胚胎发育过程中，脑血管的发育主要是通过血管发生（angiogenesis），而在成年人类和啮齿动物脑内，新生血管的生成则只在如低氧、缺血等病理生理条件下发生，原先存活的毛细血管经发芽或潜在吻合血管枝增大形成新血管，过程包括内皮细胞趋化移动、增殖，形成新管腔，周细胞、血管平滑肌细胞等血管周围细胞的移入、黏附至内皮层形成完整的血管壁；血管丛经重塑（修剪）形成成熟的血管系统等。在新生血管生成过程中，两条调节途径起到非常重要的作用：一条是血管内皮生长因子（vascular endothelial growth factor，VEGF）及其受体（flt-1等）调节通路，另一条是血管生成素（angiopoietin，Ang）及其受体（Tie）调节通路，这两条途径协同作用，共同促进机体血管形成。     

超声联合微泡诱导血管平滑肌细胞凋亡的机制研究

目的 探讨低频超声联合脂质微泡诱导血管平滑肌细胞(VSMCs)凋亡的可能机制.方法 以低频连续波超声(频率1 MHz、声强0.3 W/cm2)联合脂质微泡(1 μl/ml)辐照VSMCs 120 s.分别用流式细胞仪Annexin V/PI染色、免疫细胞化学技术、荧光探针Fura-4/Am负载后激光共聚焦法检测细胞凋亡、凋亡相关蛋白表达和细胞内游离Ca2 浓度的变化情况.结果 与对照组和血小板衍生生长因子-BB刺激组(PDGF)比较,两组超声辐照联合微泡[(US MB)组和(PDGF US MB)组]的VSMCs凋亡率显著增加、Bax蛋白表达明显上调、而Bcl-2蛋白表达则显著减少(P<0.01);而且PDGF US MB组的细胞凋亡率明显高于US MB组,Bax蛋白表达上调和Bcl-2蛋白表达下调的程度较US MB组更为显著(P<0.01).各实验干预组VSMCs内Ca2 浓度均较对照组显著增高(P<0.01);PDGF US MB组和US MB组细胞内Ca2 浓度均明显低于PDGF组(P<0.01).结论 超声联合微泡诱导VSMCs凋亡的机制可能与细胞内游离Ca2 浓度增加、Bax蛋白表达增加和Bcl-2蛋白表达降低有关.     

丹参酮ⅡA对AngⅡ诱导的大鼠血管平滑肌细胞增殖的影响

目的：探讨丹参酮ⅡA（TSN）对血管紧张素Ⅱ（AngⅡ）诱导的大鼠血管平滑肌细胞增殖的影响,以寻找药物作用的靶点。方法：分离大鼠胸主动脉中层平滑肌,贴壁法培养平滑肌细胞,建立AngⅡ诱导的血管平滑肌细胞（VSMC）增殖模型;以四甲基偶氮唑蓝（MTT）法观察丹参酮ⅡA对VSMC增殖的影响;用酶促反应定磷法测定钙调神经磷酸酶（CaN）活性;应用免疫细胞化学法观察原癌基因c-fos和c-myc的表达。结果：成功建立AngⅡ诱导的VSMC增殖模型;随着TSN浓度增加VSMC增殖活性呈明显下降趋势（P〈0.05,0.01）;TSN各组随着浓度的增加,VSMC中CaN活性显著下降（P〈0.01）,VSMC中c-fos和c-myc表达水平也显著下降（P〈0.01）。结论：TSN能抑制血管平滑肌细胞的增殖,并呈浓度依赖性。其机制可能与下调VSMC中CaN活性、c-fos及c-myc表达有关。     

血管内皮生长因子在脑复发胶质瘤中的表达

背景：脑胶质瘤病灶介质中富含新生血管，血管内皮生长因子表达不同可能与其病理表现和复发存在一定的相关性。 目的：分析血管内皮生长因子在复发脑胶质瘤中表达的特征。 设计：对照实验。 单位：四川大学华西医院神经外科。 对象：从华西医院1996—06／2001—06手术切除且病理证实为脑胶质瘤143例石蜡标本中，收集临床资料完整且相同的个体复发前、后脑胶质瘤标本44例（22对）。取首次手术及第1次复发手术标本。其中Kernohan评分Ⅰ级8例；Ⅱ级10例；Ⅲ级14例；Ⅳ级12例。分为初发和复发2组，每组22例。 方法：采用免疫组织化学SP法，一抗羊抗人血管内皮生长因子IgG（单抗）、二抗兔抗羊IgG，工作度1：50，阴性对照为磷酸盐缓冲液置换一抗染色。检测44例复发前、后的脑胶质瘤病理组织中血管内皮生长因子蛋白表达水平，结合病理分级作对照分析。①胞浆内呈棕黄色颗粒为阳性信号。②在MPIAS-500型多媒体彩色病理图文分析系统上，对肿瘤细胞进行表达强度PU值（阳性单位）和细胞数测定。③PU值95％临界值，分别计数阳性细胞率。④常规苏木精一伊红染色Kemohan病理分级。 主要观察指标：①脑胶质瘤复发前、后标本血管内皮生长因子表达强度PU值。②脑胶质瘤复发前、后组病理分级。结果：①脑胶质瘤血管内皮生长因子表达强度PU值：初发组为21．9273&;#177;6．607，复发组为33．0545&;#177;6．684。②病理分级：初发Ⅰ级8例，复发Ⅱ级2例、Ⅲ级5例、Ⅳ级1例；初发Ⅱ级6例，复发Ⅱ级2例、Ⅲ级1例、Ⅳ级3例；初发Ⅲ级6例，复发Ⅲ级2例、Ⅳ级4例；初发Ⅳ级2例，复发Ⅳ级2例。③脑胶质瘤复发前、后标本血管内皮生长因子蛋白表达PU值和肿瘤复发前、后病理分级各自对比检验差异均有显著性（P〈0．05）。 结论：血管内皮生长因子表达强度在脑胶质瘤复发较初发时增加明显，复发肿瘤恶化趋势与血管内皮生长因子的高表达在胶质瘤的复发中呈一致性。     

miRNA-146a调控血管平滑肌细胞增殖和凋亡的作用及机制

目的探究miRNA-146a调控血管平滑肌细胞增殖、凋亡的作用及相关机制。方法取SDP级健康雄性SD大鼠作为实验对象,取血管平滑肌细胞(VSMC)消化离心后,转染50nmol/L miRNA-146a反义寡核苷酸、错义链和同等剂量磷酸盐缓冲液(PBS),进行对照比较。结果实验组细胞在转染后48h内VSMC的数目和吸光度值均低于其他两组,细胞凋亡率明显高于其他两组,核因子κBp65、PCNA的表达水平低于其他两组,差异均具有统计学意义(P0.05)。结论miRNA-146a可促进VSMC的增殖,抑制细胞凋亡的进行,这一作用机制与核因子κBp65、PCNA表达水平增高有关。     

血管生成因子在脑动静脉血管畸形发生发展过程中的生物学效应

目的：观察脑动静脉血管畸形发生发展过程中血管生成因舌的作用。方法：收集天津医科大学总医院神经外科1999—08／2001-05手术切除的完整脑动静脉畸形新鲜标本47例（Spetzler Ⅰ-Ⅴ级），其中以出血为首发症状者28例，癫痫5例，头痛7例，局灶性神经功能缺失7例：另取外伤内减压术切除的正常脑组织8例作为对照。采用免疫组化方法检测脑动静脉血管畸形标本中血管内皮细胞生长因子、Tie受体、血管生成素1、血管生成素2、原癌基因c-myc和增殖细胞核抗原的表达情况。结果：脑动静脉血管畸形标本中血管内皮细胞表达极低水平的Tie受体1和血管生成素1，但血管内皮细胞生长因子、Tie受体2、血管生成素2、c—myc和增殖细胞核抗原表达上调，并随脑动静脉血管畸形的Spetzler-Martin分级升高而递增，与对照组比较差异有显著性（P〈0．05），其中血管内皮细胞生长因子与c—myc和增殖细胞核抗原表达呈正相关（r=0．728-0．916，P〈0．05）。出血组较未出血组血管内皮细胞生长因子、血管生成素2和增殖细胞核抗原表达显著降低（P〈0．05）。结论：血管生成因子表达与脑动静脉血管畸形发展扩大和破裂出血有重要关系，血管内皮细胞生长因子可能通过上调c-myc表达而发挥促血管生成的生物学效应。     

血管内皮生长因子基因多态性与糖尿病慢性并发症

糖尿病（diabetes）的慢性并发症涉及全身各个系统，如神经、心血管、泌尿、肌肉运动、消化系统等，微血管病变是导致这些慢性并发症的主要原因。糖尿病在增加动脉粥样硬化发病危险性的同时，也导致了视网膜病变、肾病及神经病变等特殊的微血管病变，这些病变反映了潜在的内皮功能异常。血管内皮生长因子（vascular endothelial growth factor．VEGF）是在糖尿病微血管并发症中起关键作用的一种细胞因子，又称血管通透因子（vascularpermeabilityfactor．VPF）。具有促进血管通透性增加、细胞外基质变性、血管内皮细胞迁移、增殖和血管形成等作用。缺氧、胰岛素、糖基化终产物、血管紧张Ⅱ（angiotensinII，AngII）、内毒索、生长因子等均可刺激血管平滑肌细胞、胶质细胞、内皮细胞等过度表达VEGF。近年来很多研究表明，VEGF基因多态性与糖尿病的慢性并发症有关，现简单综述如下。     

异常疤痕中血管内皮生长因子和增殖细胞核抗原的表达

目的 探讨瘢痕疙瘩和增殖性瘢痕等异常疤痕中血管作者简介：李军辉 (1970-),男,江西人,整形外科讲师,硕士,研究方向：异常疤痕防治。 内皮生长因子（ VEGF）和增殖细胞核抗原（ PCNA）的表达及其意义。方法 应用免疫组织化学染色技术,以正常皮肤和正常瘢痕作对照,观察了瘢痕疙瘩和增殖性瘢痕中 VEGF和 PCNA的表达。结果 瘢痕疙瘩和增殖性瘢痕基底层角朊细胞均大量表达 VEGF,较正常皮肤和正常瘢痕显著增加。 PCNA的表达与 VEGF相似,但真皮内少量的成纤维细胞有较弱的 PCNA表达。结论 瘢痕疙瘩和增殖性瘢痕表皮基底层的角朊细胞大量表达 VEGF和 PCNA可能与异常疤痕的形成密切相关。     

Inhibition of vascular smooth muscle cell proliferation in vitro and in vivo by c-myc antisense oligodeoxynucleotides.

Restenosis after angioplasty is due predominantly to accumulation of vascular smooth muscle cells (VSMCs). The resistance of restenosis to pharmacological treatment has prompted investigation of genes involved in VSMC proliferation. We have examined the effect on VSMC proliferation of blocking expression of the c-myc proto-oncogene with antisense oligodeoxynucleotides, both in vitro and in a rat carotid artery injury model of angioplasty restenosis. Antisense c-myc oligodeoxynucleotides reduced average cell levels of c-myc mRNA and protein by 50-55% and inhibited proliferation of VSMCs when mitogenically stimulated from quiescence or when proliferating logarithmically (IC50 = 10 micrograms/ml). Corresponding sense c-myc, two-base-pair mismatch antisense c-myc, antisense alpha-actin or glyceraldehyde phosphate dehydrogenase oligodeoxynucleotides did not suppress c-myc expression or inhibit VSMC proliferation. Antisense c-myc inhibition was relieved by overexpression of an exogenous c-myc gene. After balloon catheter injury, peak c-myc mRNA expression occurred at 2 h. Antisense c-myc applied in a pluronic gel to the arterial adventitia reduced peak c-myc expression by 75% and significantly reduced neointimal formation at 14 d, compared with sense c-myc and gel application alone. We conclude that c-myc expression is required for VSMC proliferation in vitro and in the vessel wall. C-myc is a therefore a potential target for adjunctive therapy to reduce angioplasty restenosis.     

Fibroblast growth factor stimulates angiotensin converting enzyme expression in vascular smooth muscle cells. Possible mediator of the response to vascular injury.

Angiotensin converting enzyme (ACE) activity contributes to the vascular response to injury because ACE inhibition limits neointima formation in rat carotid arteries after balloon injury. To investigate the mechanisms by which ACE may contribute to vascular smooth muscle cell (VSMC) proliferation, we studied expression of ACE in vivo after injury and in vitro after growth factor stimulation. ACE activity 14 d after injury was increased 3.6-fold in the injured vessel. ACE expression, measured by immunohistochemistry, became apparent at 7 d in the neointima and at 14 d was primarily in the most luminal neointimal cells. To characterize hormones that induce ACE in vivo, cultured VSMC were exposed to steroids and growth factors. Among steroids, only glucocorticoids stimulated ACE expression with an 8.0 +/- 2.1-fold increase in activity and a 6.5-fold increase in mRNA (30 nM dexamethasone for 72 h). Among growth factors tested, only fibroblast growth factor (FGF) stimulated ACE expression (4.2 +/- 0.7-fold increase in activity and 1.6-fold increase in mRNA in response to 10 ng/ml FGF for 24 h). Dexamethasone and FGF were synergistic at the indicated concentrations inducing 50.6 +/- 12.4-fold and 32.5-fold increases in activity and mRNA expression, respectively. In addition, when porcine iliac arteries were transfected with recombinant FGF-1 (in the absence of injury), ACE expression increased in neointimal VSMC, to the same extent as injured, nontransfected arteries. The data suggest a temporal sequence for the response to injury in which FGF induces ACE, ACE generates angiotensin II, and angiotensin II stimulates VSMC growth in concert with FGF.     

Adenovirus-mediated over-expression of the cyclin/cyclin-dependent kinase inhibitor, p21 inhibits vascular smooth muscle cell proliferation and neointima formation in the rat carotid artery model of balloon angioplasty.

Vascular smooth muscle cell (VSMC) proliferation after arterial injury is important in the pathogenesis of a number of vascular proliferative disorders, including atherosclerosis and restenosis after balloon angioplasty. Thus, a better understanding of the molecular mechanisms underlying VSMC proliferation in response to arterial injury would have important therapeutic implications for patients with atherosclerotic vascular disease. The p21 protein is a negative regulator of mammalian cell cycle progression that functions both by inhibiting cyclin dependent kinases (CDKs) required for the initiation of S phase, and by binding to and inhibiting the DNA polymerase delta co-factor, proliferating cell nuclear antigen (PCNA). In this report, we show that adenovirus-mediated over-expression of human p21 inhibits growth factor-stimulated VSMC proliferation in vitro by efficiently arresting VSMCs in the G1 phase of the cell cycle. This p21-associated cell cycle arrest is associated both with significant inhibition of the phosphorylation of the retinoblastoma gene product (Rb) and with the formation of complexes between p21 and PCNA in VSMCs. In addition, we demonstrate that localized arterial infection with a p21-encoding adenovirus at the time of balloon angioplasty significantly reduced neointimal hyperplasia in the rat carotid artery model of restenosis. Taken together, these studies demonstrate the important role of p21 in regulating Rb phosphorylation and cell cycle progression in VSMC, and suggest a novel cytostatic gene therapy approach for restenosis and related vascular proliferative disorders.     

Role of GADD153 (growth arrest- and DNA damage-inducible gene 153) in vascular smooth muscle cell apoptosis

GADD153 (growth arrest- and DNA damage-inducible gene 153) is expressed at very low levels in growing cells, but is markedly induced in response to a variety of cellular stresses, including glucose deprivation, exposure to genotoxic agents and other growth-arresting situations. Forced expression of GADD153 induces cell cycle arrest in many types of cells. It is also reported that GADD153 is directly associated with apoptosis. Recently we have reported that platelet-derived growth factor (PDGF)-BB induces apoptosis in cultured vascular smooth muscle cells (VSMC), but only when 100% confluency is reached. These results suggested that cell-cell contact inhibition (cell growth arrest) may be a critical factor for induction of VSMC apoptosis by PDGF-BB. In the present study, we explored the role of GADD153, one of a number of growth-arrest-related gene products, in the molecular mechanisms of VSMC apoptosis in vitro and in vivo. GADD153 was markedly induced at both the mRNA and protein levels, in parallel with the induction of VSMC apoptosis, after treatment with PDGF-BB. Moreover, overexpression of GADD153 in VSMC significantly reduced cell viability and induced apoptosis. In the carotid artery balloon injury model in rats, GADD153 protein was expressed in apoptotic VSMC which were positively stained by in situ DNA labelling. These results demonstrate an important role for GADD153 in the molecular mechanisms of VSMC apoptosis.     

Taxol inhibits neointimal smooth muscle cell accumulation after angioplasty in the rat.

Despite significant improvements in the primary success rate of the medical and surgical treatments for atherosclerotic disease, including angioplasty, bypass grafting, and endarterectomy, secondary failure due to late restenosis continues to occur in 30-50% of individuals. Restenosis and the later stages in atherosclerotic lesions are due to a complex series of fibroproliferative responses to vascular injury involving potent growth-regulatory molecules (such as platelet-derived growth factor and basic fibroblast growth factor) and resulting in vascular smooth muscle cell (VSMC) proliferation, migration, and neointimal accumulation. We show here, based on experiments with both taxol and deuterium oxide, that microtubules are necessary for VSMCs to undergo the multiple transformations contributing to the development of the neointimal fibroproliferative lesion. Taxol was found to interfere both with platelet-derived growth factor-stimulated VSMC migration and with VSMC migration and with VSMC proliferation, at nanomolar levels in vitro. In vivo, taxol prevented medial VSMC proliferation and the neointimal VSMC accumulation in the rat carotid artery after balloon dilatation and endothelial denudation injury. This effect occurred at plasma levels approximately two orders of magnitude lower than that used clinically to treat human malignancy (peak levels achieved in this model were approximately 50-60 nM). Taxol may therefore be of therapeutic value in preventing human restenosis with minimal toxicity.     

线粒体融合素2基因突变体对大鼠颈动脉球囊损伤后内膜增生的影响

目的 探讨线粒体融合素2(mitofusin 2,Mfn 2)基因蛋白激酶A(PKA)磷酸化位点突变体对大鼠颈动脉球囊损伤后内膜增生的影响.方法 建立大鼠颈动脉球囊损伤模型,感染组分别以携带全长Mfn2基因的重组腺病毒(Adv-Mfn2)、携带不同Mfn2基因突变体的重组腺病毒(Adv-Mfn2-S442A,Adv-Mfn2-S442D)和仅含有半乳糖苷酶基因的对照腺病毒(Adv-LacZ)感染损伤的颈总动脉段,以磷酸盐缓冲液(PBS)作为未感染对照组,同时以假手术组作为正常对照组.术后14 d取材,采用HE染色、Image-Pro plus图像分析系统进行形态学分析,同时,应用免疫组化检测Mfn2蛋白和细胞增殖核抗原(PCNA)表达,应用方差分析和Dunnett-t检验行统计学分析.结果 术后14 d,免疫组化证实Adv-Mfn2、Adv-Mfn2-S442A、Adv-Mfn2-S442D组Mfn2总蛋白表达水平明显增加;HE染色和PCNA染色结果显示,Adv-Mfn2组、Adv-Mfn2-S442A组内膜/中膜面积比(I/M)和PCNA阳性细胞率明显低于Control组(P＜0.01);与Adv-Mfn2组相比,Adv-Mfn2-S442A组I/M值和PCNA阳性细胞率更低(P＜0.01);Aay-LdacZ组和Adv-Mfn2-S442D组与Control组相比差异无统计学意义(P＞0.05).结论 高表达Mfn2基因可抑制大鼠颈动脉球囊损伤后内膜增生,且Mfn2基因突变体Mfn2-S442A抑制作用更强,而Mfn2-S442D则无抑制作用.     

A complex role for the progesterone receptor in the response to vascular injury

Clinical studies of hormone replacement therapy to prevent cardiovascular diseases have heightened interest in the cardiovascular effects of progestins. However, the role of the progesterone receptor (PR) in vascular biology has not been studied in vivo. We studied ovariectomized female PR knockout (PRKO) mice and their wild-type (WT) littermates using the mouse carotid artery injury model. Placebo-treated PRKO mice showed significantly greater vascular medial hypertrophy and vascular smooth muscle cell (VSMC) proliferation in response to vascular injury than did WT mice. Progesterone had no significant effect in the PRKO mice, but worsened the response to injury in WT mice. VSMCs cultured from PRKO mouse aortae were markedly hyperproliferative, and their growth was not affected by progesterone. In contrast to the in vivo findings, progesterone inhibited proliferation of WT-derived VSMCs. Furthermore, reintroduction of PR into PRKO-derived VSMCs using adenoviral methods restored progesterone-mediated inhibition of proliferation to these cells. This effect was reversed by the PR antagonist, RU 486. Thus, the effects of PR and progesterone differ markedly between cultured VSMCs and intact blood vessels. These data demonstrate a direct role for the PR in regulating the response to vascular injury and VSMC proliferation.     

Infusion of platelet-derived growth factor or basic fibroblast growth factor induces selective glomerular mesangial cell proliferation and matrix accumulation in rats.

Mesangial cell (MC) proliferation and extracellular matrix expansion are involved in the pathogenesis of glomerulosclerosis and renal failure. In vitro, PDGF and basic fibroblast growth factor (bFGF) regulate MC proliferation and/or matrix production. To elucidate the role of PDGF and bFGF in vivo, equimolar concentrations of recombinant PDGF-BB or bFGF or vehicle were infused intravenously into rats over a 7-d period. Rats were either nonmanipulated ("normals") or had received a subnephritogenic dose of anti-MC antibody ("anti-Thy 1.1 rats") before the infusion period. Glomerular cell proliferation (anti-proliferating cell nuclear antigen immunostaining) on days 2, 4, and 7 was unchanged in vehicle-infused normals or anti-Thy 1.1 rats. PDGF infusion increased glomerular cell proliferation 32-fold in anti-Thy 1.1 rats and an 11-fold in normals on day 2. bFGF increased glomerular cell proliferation fourfold in anti-Thy 1.1 rats but was ineffective in normals. Induction of cell proliferation in all kidneys was limited to the glomerulus. The majority of proliferating cells were identified as MC by double immunolabeling. No significant proteinuria, glomerular leukocyte, or platelet influx developed in any group. Glomerular matrix expansion with increased deposition of type IV collagen, laminin, and fibronectin, as well as upregulated laminin and collagen IV mRNA expression was confined to PDGF-infused anti-Thy 1.1 rats. These results show that PDGF and, to a lesser degree, bFGF are selective MC mitogens in vivo and that previous subclinical injury can enhance this MC response. The data thereby support a role of these cytokines in the pathogenesis of glomerulosclerosis.