苯那普利对糖尿病大鼠肾小球MMP-9影响的实验研究

目的探讨苯那普利对糖尿病大鼠肾小球基质金属蛋白酶-9（MMP-9）表达的影响。方法将雄性SD大鼠30只,随机抽出10只动物作为正常对照组（C组）,其余20只采用腹腔注射STZ制备糖尿病大鼠模型。将这20只造模成功的糖尿病大鼠模型随机分为2组：糖尿病组（DM组）和药物处理组（DB组）。其中药物处理组即DB组大鼠每天应用苯那普利进行治疗性灌胃,C组和DM组用等量自来水灌胃。分别于治疗4、8周后,测定皿糖和内生肌苷清除率,用代谢笼收集24h尿量。利用免疫组织化学染色及图像分析方法,对MMP-9在肾组织不同时间点的含量变化进行定性分析。结果苯那普利治疗组血糖水平和内生肌苷清除率明显降低,与糖尿病模型组相比有显著性差异。免疫组织化学染色显示：MMP-9在正常肾小球有阳性表达;DM组大鼠病程第8周时,MMP-9在肾小球表达明显减弱;DB组大鼠病程第8周时,经苯那普利治疗后,与同期糖尿病组比较表达明显上调。图像分析方法定量分析免疫组织化学染色阳性面积百分比,苯那普利治疗后第4周和第8周糖尿病肾病的大鼠肾小球MMP-9的阳性面积百分比分别为25．55％±3．44％和20．10％±2．11％,与糖尿病组对比有明显的提高（P〈0．01）。结论MMP-9在糖尿病肾小球中的表达随病程进展逐渐减弱,苯那普利可能部分通过上调MMP-9在肾小球中的表达起到保护肾脏的作用。     

转化生长因子β1和Snaill参与糖尿病大鼠肾小管上皮细胞向间充质细胞转变

本文旨在观察转化生长因子β1(transforming growth factor-β1,TGF-β1)和锌指转录因子Snaill在糖尿病(diabetesmellitus,DM)大鼠.肾组织中的表达,并初步探讨它们与肾小管上皮细胞向间充质细胞转变的关系.链脲佐菌素(streptozotocin,STZ)诱发大鼠DM,按病程分为2、4、8、12、16、20、24周、16周胰岛素治疗(16wA)、20周胰岛素治疗(20wA)和24周胰岛索治疗(24wA)组(n=6).其中胰岛素治疗组动物从第13周起用胰岛素控制血糖至正常水平,每一时点均设鼠龄匹配的正常对照组.测定各组血糖、24 h尿蛋白、血肌酐(serum creatinine,Scr)、肾脏指数.PAS染色光镜观察肾脏病理学改变.免疫组织化学检测肾脏SnMll、TGF-β1、α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)、E-钙黏素和纤连蛋白(fibronectin,FN)的表达;Western blot检测肾皮质SnailI、TGF-β1和E-钙黏素蛋白表达.RT-PeR检测肾皮质Snaill和E-钙黏素mRNA表达.结果显示:(1)DM各组大鼠的血糖、24 h尿蛋白、Scr、肾脏指数均较正常对照组明显升高(P<0.05,P<0.01),胰岛素治疗组大鼠上述指标均较DM组显著降低(P<0.01).(2)TGF-β1和Snmll免疫组织化学阳性染色见于DM各组大鼠肾小管,正常对照组未见阳性表达,胰岛素治疗组大鼠弱阳性表达,并随治疗时间延长而减少.从16周开始在DM大鼠肾小管上皮细胞可见α-SMA蛋白阳性表达,胰岛素治疗组大鼠未见α-SMA蛋白表达;DM组大鼠E-钙黏素蛋白阳性染色明显少于正常对照组.(3)DM组大鼠肾皮质TGF-β和Snaill蛋白以及Snaill mRNA表达较正常对照组显著增高(P<0.01),胰岛素治疗组大鼠则显著低于DM组(P<0.01);DM组E.钙黏素mRNA和蛋白表达与TGF-β1和Snaill呈相反变化.结果提示,TGF-βl和Snaill可能参与DM大鼠肾小管上皮细胞向问充质细胞转变,胰岛素治疗可抑制两者表达并阻断肾小管上皮细胞向间充质细胞转变.     

内质网应激及其特有凋亡途径Caspase-12与糖尿病大鼠肾组织固有细胞凋亡之间的关系

目的：检测内质网应激（ERS）标志蛋白在糖尿病大鼠肾组织的表达及其与细胞凋亡之间的关系。方法：单侧肾切除大鼠腹腔注射链脲佐菌素诱发糖尿病,于8周应用免疫组织化学检测GRP78、Caspase-12、PCNA的表达与定位,TUNEL染色检测细胞凋亡部位,流式细胞术检测细胞凋亡程度,并对GRP78、Caspase-12表达水平进行半定量分析,同时观察尿蛋白、BUN、尿肌酐等反应肾功能的相关指标。结果：建模8周,糖尿病组大鼠较对照组肾小球、肾小管凋亡细胞数明显增多,GRP78、Caspase-12表达显著增强。PCNA表达与对照组无明显差异。结论：糖尿病肾损害过程中,ERS被诱导并可能通过激活其特有的凋亡途径Caspase-12引起肾脏细胞过多丢失在糖尿病肾病的发病机制中起重要作用。     

实验性肝硬化大鼠肠上皮细胞间紧密连接蛋白occludin表达下降

目的研究实验性肝硬化大鼠大肠上皮细胞间紧密连接蛋白occludin表达的变化。方法参照文献1,给大鼠反复腹腔注射CCl4制备化学性肝硬化大鼠动物模型。实验4周、8周分批处死动物,应用免疫组织化学及Western blot检测肝硬化进程中,大鼠大肠上皮细胞间紧密连接蛋白occludin的定位及表达的变化。结果occludin蛋白主要沿大鼠大肠粘膜上皮细胞膜的顶端呈线状分布,在肝硬化组大鼠,4周时occludin的阳性染色开始减少,8周时更为明显。Western blot结果与免疫组织化学结果相一致,4周时开始下降(0.51±0.07),8周时达到最低值(0.32±0.05),与对照组(0.83±0.09)相比差异显著(P<0.05)。结论在肝硬化进程中,大肠上皮细胞间紧密连接蛋白occludin表达下降。     

转化生长因子β1和snail1参与糖尿病大鼠肾小管上皮细胞向间充质细胞转变

本文旨在观察转化生长因子β1（transforming growth factor-β1,TGF-β1）和锌指转录因子Snail1在糖尿病（diabetes mellitus,DM）大鼠肾组织中的表达,并初步探讨它们与肾小管上皮细胞向间充质细胞转变的关系。链脲佐菌素（streptozotocin,STZ）诱发大鼠DM,按病程分为2、4、8、12、16、20、24周、16周胰岛素治疗（16wA）、20,周胰岛素治疗（20wA）和24周胰岛素治疗（24wA）组（n=6）。其中胰岛素治疗组动物从第13周起用胰岛素控制血糖至正常水平,每一时点均设鼠龄匹配的正常对照组。测定各组血糖、24h尿蛋白、血肌酐（serum creatinine,Scr）、肾脏指数。PAS染色光镜观察肾脏病理学改变。免疫组织化学检测肾脏Snail1、TGF-β1、α-平滑肌肌动蛋白（α-smooth muscle actin,α-SMA）、E-钙黏素和纤连蛋白（fibronectin,FN）的表达;Western blot检测肾皮质Snail1、TGF-β1和E-钙黏素蛋白表达。RT-PCR检测肾皮质Snail1和E-钙黏素mRNA表达。结果显示：（1）DM各组大鼠的血糖、24h尿蛋白、Scr、肾脏指数均较正常对照组明显升高（P〈0．05,P〈0．01）,胰岛素治疗组大鼠上述指标均较DM组显著降低（P〈0．01）。（2）TGF-β1和Snail1免疫组织化学阳性染色见于DM各组大鼠肾小管,正常对照组未见阳性表达,胰岛素治疗组大鼠弱阳性表达,并随治疗时间延长而减少。从16周开始在DM大鼠肾小管上皮细胞可见α-SMA蛋白阳性表达,胰岛素治疗组大鼠未见α-SMA蛋白表达;DM组大鼠E-钙黏素蛋白阳性染色明显少于正常对照组。（3）DM组大鼠肾皮质TGF-β1和Snail1蛋白以及Snail1 mRNA表达较正常对照组显著增高（P〈0．01）,胰岛素治疗组大鼠则显著低于DM组（P〈0．01）;DM组E-钙黏素mRNA和蛋白表达与TGF-β1和Snail1呈相反变化。结果提示,TGF-β1和Snail1可能参与DM大鼠肾小管上皮细胞向间充质细胞转变,胰岛素治疗可抑制两者表达并阻断肾小管上皮细胞向间充质细胞转变。     

硫化氢对1型糖尿病大鼠肾脏的保护作用

目的：观察硫化氢（H₂S）对1型糖尿病大鼠肾脏的保护作用及其机制。方法：32只雄性SD大鼠随机分为4组：正常对照（NC）组、糖尿病（DM）组、糖尿病治疗（NaHS+DM）组和NaHS对照（NaHS）组（n=8）。DM组和NaHS+DM组大鼠采用链脲佐菌素（STZ）55 mg/kg腹腔注射诱导1型糖尿病模型。造模成功后,NaHS+DM组和NaHS组采用腹腔注射NaHS溶液56 μmol/kg干预治疗。8周后,测定大鼠24 h尿蛋白含量、肾重指数、空腹血糖、尿素氮、肌酐等指标;HE染色观察肾脏组织形态学变化;测定肾脏组织脂质过氧化物丙二醛（MDA）含量、超氧化物歧化酶（SOD）和Caspase-3的活性;Western blot检测肾脏组织Bcl-2和Bax蛋白表达。结果：与NC组相比,NaHS组各项指标均无显著差异,DM组,24 h尿蛋白含量、肾重指数、空腹血糖、尿素氮和肌酐水平均明显升高;HE染色结果显示肾小球基底膜增厚、系膜基质增多;MDA含量、Caspase-3活性和Bax蛋白表达明显增高;SOD活性和Bcl-2蛋白表达显著降低。与DM组相比,NaHS+DM组肾功能损伤明显减轻,肾脏组织形态学变化明显改善,MDA含量、Caspase-3活性和Bax蛋白表达明显下降,SOD活性和Bcl-2蛋白表达显著增高。结论：H₂S对1型糖尿病大鼠肾脏具有保护作用,其机制可能与抑制氧化应激和细胞凋亡有关。     

葛根素对糖尿病大鼠肾组织MMP-2的表达及活性的影响

为探讨葛根素对糖尿病大鼠肾组织基质金属蛋白酶2(MMP-2)及活性表达的影响,采用单侧肾切除大鼠ip链脲佐菌素诱发糖尿病模型的方法,每日ip葛根素注射液,共16周。采用原位杂交法检测肾小球MMP-2、TIMP-2mRNA表达,流式细胞术和免疫组织化学检测肾皮质MMP-2、TIMP-2及Ⅳ型胶原表达;酶谱分析检测肾皮质MMP-2活性变化。结果发现糖尿病组较对照组肾小球MMP-2mRNA及蛋白表达降低而TIMP-2mRNA及蛋白表达升高,Ⅳ型胶原表达亦增加,MMP-2活性降低,肾功能恶化;葛根素用药组较糖尿病组MMP-2mRNA及蛋白表达升高而TIMP-1、Ⅳ型胶原表达减少,MMP-2活性部分恢复,肾功能改善。表明葛根素可能部分是通过调节肾小球MMP-2蛋白表达及活性的改变从而减轻肾小球细胞外基质沉积,保护糖尿病大鼠的肾功能和形态。     

MMP1 在炎症大鼠牙髓组织中表达

目的:探讨基质蛋白酶MMP-1在炎症性牙髓中的表达。方法:内毒素制备大鼠牙髓炎模型,取牙髓炎大鼠及健康大鼠牙髓组织行HE染色检测牙髓组织的组织形态学变化,MMP-1特异性免疫组织化学染色和Western blot等检测MMP-1在牙髓组织的表达,以明确MMP-1在大鼠急性牙髓炎期的空间分布改变及蛋白表达量变化。结果:大鼠牙髓组织急性炎症期牙髓炎模型中可见大量炎性细胞浸润,结缔组织有断裂破坏。免疫组织化学分析及Western Blot分析均显示牙髓炎组织MMP-1蛋白显著增高(P0.05)。结论:MMP-1在牙髓炎组织中高表达,可能参与调节牙髓炎症反应的疼痛机制调节。     

糖尿病大鼠心肌功能的改变及其机制*

目的:观察钙敏感受体(CaSR)表达变化在2型糖尿病大鼠心功能降低中的作用。方法:Wistar大鼠随机分成3组:对照组、糖尿病4周和8周组。糖尿病组大鼠给予高糖高脂饮食喂养,4周后腹腔注射链脲佐菌素建立2型糖尿病模型。通过HE染色观察心脏形态学变化,通过超声心动仪检测心脏功能的变化,通过Western blot检测心肌组织CaSR和PKC-α蛋白表达的变化。结果:与对照组相比,糖尿病大鼠心脏收缩和舒张功能降低,心肌组织出现不规则收缩带,且随着病程延长逐渐加重,同时心肌组织CaSR和PKC-α蛋白表达减少。结论:糖尿病大鼠心肌CaSR等蛋白的表达降低,从而引起细胞内钙紊乱,导致心功能下降。     

槐果碱抑制糖尿病大鼠肾损伤、NLRP3炎性小体和NF-κB通路活化

目的 观察槐果碱（sophocarpine, SC）对糖尿病大鼠肾损伤的影响,并探讨其相关机制。方法 选用SD大鼠,以高脂饮食12周和链脲佐菌素处理制作糖尿病模型,灌胃给予槐果碱治疗12周。PAS染色以及纤连蛋白（fibronectin, FN）和Cleaved Caspase-3免疫组织化学染色评估肾组织损伤,ELISA检测肾组织中IL-1β及IL-6水平,Western blot检测肾组织中NLRP3、凋亡相关斑点样蛋白（apoptosis-associated speck-like protein containing CARD, ASC）、Cleaved Caspase-1和NF-κB p65蛋白表达水平。结果 糖尿病大鼠肾重指数、尿蛋白排泄水平、血清尿酸水平、肾小球系膜基质扩张系数均较对照大鼠明显升高,肾组织中FN、Cleaved Caspase-3、IL-1β、IL-6、NLRP3、ASC、Cleaved Caspase-1和NF-κB p65蛋白水平均较对照大鼠明显上调,槐果碱干预能明显抑制糖尿病大鼠上述指标变化。结论 槐果碱可能通过抑制NLRP3炎性小体和NF-κB通路...     

The cardiac neural stem cell phenotype is compromised in streptozotocin‐induced diabetic cardiomyopathy

Neural stem cells were identified in the rat heart and during scar formation and healing participated in sympathetic fiber sprouting and angiogenesis. In the setting of diabetes, impaired wound healing represents a typical pathological feature. These findings provided the impetus to test the hypothesis that experimental diabetes adversely influenced the phenotype of cardiac neural stem cells. Streptozotocin (STZ)‐induced diabetic rats were associated with elevated plasma glucose levels, significant loss of body weight and left ventricular contractile dysfunction. In the heart of STZ‐diabetic rats, the density of nestin immunoreactive processes emanating from cardiac neural stem cells were reduced. The latter finding was reaffirmed as nestin protein expression was significantly decreased in the heart of STZ‐diabetic rats and associated with a concomitant reduction of nestin mRNA. Employing the TUNEL assay, the loss of nestin expression in STZ‐diabetic rats was not attributed to widespread cardiac neural stem cell apoptosis. Insulin administration to STZ‐diabetic rats with established hyperglycaemia led to a modest recovery of nestin protein expression in cardiac neural stem cells. By contrast, the administration of insulin immediately after STZ injection improved plasma glucose levels and significantly attenuated the loss of nestin protein expression. These data highlight the novel observation that nestin protein expression in cardiac neural stem cells was significantly reduced in STZ‐induced type I diabetic rats. The aberrant cardiac neural stem cell phenotype may compromise their biological role and predispose the diabetic heart to maladaptive healing following ischemic injury. J. Cell. Physiol. 220: 440–449, 2009. © 2009 Wiley‐Liss, Inc.     

Nestin protects mouse podocytes against high glucose-induced apoptosis by a Cdk5-dependent mechanism

Podocyte apoptosis contributes to the pathogenesis of diabetic nephropathy (DN). However, the mechanisms that mediate hyperglycemia‐induced podocyte apoptosis remain poorly understood. Recent findings indicate that the disruption of the cytoskeleton is related to the podocyte apoptosis. In the present study, we investigated the involvement of nestin, an important cytoskeleton‐associated class VI intermediate filament (IF) protein, in the high glucose (HG)‐induced podocyte apoptosis. Our data showed that HG decreased the expression level of nestin, either mRNA or protein, in a time‐dependent manner in cultured podocytes. Also, through knockdown of nestin expression by miRNA interference, the HG‐induced podocyte apoptotic rate was significantly increased. The expression of cleaved caspase‐3 was also markedly elevated. Considering that nestin is a substrate of cyclin‐dependent kinase 5 (Cdk5), we further assessed the expression of Cdk5 in HG‐treated podocytes. The results showed that HG stimulation increased the protein and mRNA expression of Cdk5 in a time‐dependent manner in cultured mouse podocytes. The protein activator of Cdk5, p35, was also increased in a time‐dependent manner by HG stimulation, and downregulation of Cdk5 by miRNA interference attenuated the nestin reduction in HG‐treated podocytes; the HG‐induced podocyte apoptosis, the increased cleaved caspase‐3 expression and the Bax/Bcl‐2 ratio were all effectively attenuated. These data suggested that nestin, which is dependent on Cdk5 regulation, plays a cytoprotective role in HG‐induced podocyte apoptosis. J. Cell. Biochem. 113: 3186–3196, 2012. © 2012 Wiley Periodicals, Inc.     

Cdk5 regulates the organization of Nestin and its association with p35

The intermediate filament protein nestin is characterized by its specific expression during the development of neuronal and myogenic tissues. We identify nestin as a novel in vivo target for cdk5 and p35 kinase, a critical signaling determinant in development. Two cdk5-specific phosphorylation sites on nestin, Thr-1495 and Thr-316, were established, the latter of which was used as a marker for cdk5-specific phosphorylation in vivo. Ectopic expression of cdk5 and p35 in central nervous system progenitor cells and in myogenic precursor cells induced elevated phosphorylation and reorganization of nestin. The kinetics of nestin expression corresponded to elevated expression and activation of cdk5 during differentiation of myoblast cell cultures and during regeneration of skeletal muscle. In the myoblasts, a disassembly-linked phosphorylation of Thr-316 indicated active phosphorylation of nestin by cdk5. Moreover, cdk5 occurred in physical association with nestin. Inhibition of cdk5 activity-either by transfection with dominant-negative cdk5 or by using a specific cdk5 inhibitor-blocked myoblast differentiation and phosphorylation of nestin at Thr-316, and this inhibition markedly disturbed the organization of nestin. Interestingly, the interaction between p35, the cdk5 activator, and nestin appeared to be regulated by cdk5. In differentiating myoblasts, p35 was not complexed with nestin phosphorylated at Thr-316, and inhibition of cdk5 activity during differentiation induced a marked association of p35 with nestin. These results demonstrate that there is a continuous turnover of cdk5 and p35 activity on a scaffold formed by nestin. This association is likely to affect the organization and operation of both cdk5 and nestin during development.     

Expression of nestin in the podocytes of normal and diseased human kidneys

The complex cyto-architecture of the podocyte is critical for glomerular permselectivity. The present study characterizes the expression of nestin, an intermediate filament protein, in human kidneys. In normal kidneys, nestin was detected at the periphery of glomerular capillary loops. Colabeling showed nestin was expressed in WT1-positive cells. Within the podocyte, nestin immunoreactivity was present in the cell body and primary process. This was supported by immunoelectron microscopy. Nestin also colocalized with vimentin in the periphery of capillary loops but not in the mesangium. Nestin was not detected in other structures of the adult human kidney. To determine the potential role of nestin in proteinuria, nestin was examined in kidney biopsies from patients with or without proteinuria. These patients were diagnosed with IgA nephropathy with mild mesangial expansion but without proteinuria, IgA nephropathy with proteinuria, membranous nephropathy (MN), and focal segmental glomerular sclerosis (FSGS). The distribution of nestin in these biopsies was similar to that in the normal kidney. Semiquantitative analysis of immunostaining showed that glomerular nestin expression in IgA nephropathy without proteinuria was not different from normal kidney; however, nestin expression in kidneys of patients with IgA nephropathy and proteinuria, or MN and FSGS with proteinuria was significantly reduced compared with normal kidney (P < 0.01). Reduced nestin mRNA expression in the patients with IgA nephropathy with proteinuria and FSGN was also observed by quantitative real-time PCR. These studies suggest that nestin may play an important role in maintaining normal podocyte function in the human kidney.     

The Expression and Significance of Neuronal Iconic Proteins in Podocytes

Growing evidence suggests that there are many common cell biological features shared by neurons and podocytes; however, the mechanism of podocyte foot process formation remains unclear. Comparing the mechanisms of process formation between two cell types should provide useful guidance from the progress of neuron research. Studies have shown that some mature proteins of podocytes, such as podocin, nephrin, and synaptopodin, were also expressed in neurons. In this study, using cell biological experiments and immunohistochemical techniques, we showed that some neuronal iconic molecules, such as Neuron-specific enolase, nestin and Neuron-specific nuclear protein, were also expressed in podocytes. We further inhibited the expression of Neuron-specific enolase, nestin, synaptopodin and Ubiquitin carboxy terminal hydrolase-1 by Small interfering RNA in cultured mouse podocytes and observed the significant morphological changes in treated podocytes. When podocytes were treated with Adriamycin, the protein expression of Neuron-specific enolase, nestin, synaptopodin and Ubiquitin carboxy terminal hydrolase-1 decreased over time. Meanwhile, the morphological changes in the podocytes were consistent with results of the Small interfering RNA treatment of these proteins. The data demonstrated that neuronal iconic proteins play important roles in maintaining and regulating the formation and function of podocyte processes.     

Nestin as a regulator of Cdk5 in differentiating myoblasts

Many types of progenitor cells are distinguished by the expression of the intermediate filament protein nestin, a frequently used stem cell marker, the physiological roles of which are still unknown. Whereas myogenesis is characterized by dynamically regulated nestin levels, we studied how altering nestin levels affects myoblast differentiation. Nestin determined both the onset and pace of differentiation. Whereas depletion of nestin by RNAi strikingly accelerated the process, overexpression of nestin completely inhibited differentiation. Nestin down-regulation augmented the early stages of differentiation, at the level of cell-cycle withdrawal and expression of myogenic markers, but did not affect proliferation of undifferentiated dividing myoblasts. Nestin regulated the cleavage of the Cdk5 activator protein p35 to its degradation-resistant form, p25. In this way, nestin has the capacity to halt myoblast differentiation by inhibiting sustained activation of Cdk5 by p25, which is critical for the progress of differentiation. Our results imply that nestin regulates the early stages of myogenesis rather than maintains the undifferentiated state of progenitor cells. In the bidirectional interrelationship between nestin and Cdk5, Cdk5 regulates the organization and stability of its own nestin scaffold, which in turn controls the effects of Cdk5. This nestin-Cdk5 cross-talk sets the pace of muscle differentiation.     

Nestin expression is lost in ventricular fibroblasts during postnatal development of the rat heart and re-expressed in scar myofibroblasts

Studies have reported that the intermediate filament protein nestin was expressed in various non-stem/progenitor cells during development, downregulated during postnatal growth and re-expressed following injury. The present study tested the hypothesis that an analogous paradigm was prevalent for ventricular fibroblasts. In the neonatal rat heart, nestin protein levels were significantly higher than the adult heart and the isolation of cardiac cells revealed a selective expression in ventricular fibroblasts. In adult ventricular fibroblasts, nestin protein expression was markedly lower compared to neonatal ventricular fibroblasts. Following ischemic damage to the rat heart, nestin staining was detected in a subpopulation of scar myofibroblasts (37%) and the percentage of immunoreactive cells was greater than adult ventricular fibroblasts (7%) but significantly lower than neonatal ventricular fibroblasts (86%). Moreover, dissimilar rates of (3)H-thymidine uptake were observed among the fibroblast populations and may be related in part to the disparate percentage of nestin(+) cells. To assess the role of nestin in DNA synthesis, neonatal ventricular fibroblasts were infected with a lentivirus containing a shRNAmir directed against the intermediate filament protein. The partial depletion of nestin expression in neonatal ventricular fibroblasts significantly reduced basal DNA synthesis, in the absence of an apoptotic response. Thus, postnatal development of the rat heart was associated with a selective loss of nestin expression in ventricular fibroblasts and subsequent induction in a subpopulation of myofibroblasts following ischemic injury. The re-expression of nestin in scar myofibroblasts may represent an adaptive response to enhance their proliferative rate and accelerate the healing process.