RNA干扰对人瘢痕疙瘩成纤维细胞TGF-β1刺激后胶原合成的影响

目的 体外构建结缔组织生长因子(CTGF)序列特异性小干扰RNA表达载体,转染导人后研究其对人瘢痕疙瘩成纤维细胞(HKFs)胶原蛋白分泌的影响.方法 体外构建CTGF序列特异性小干扰RNA质粒表达载体,Dosper脂质体转染人瘢痕疙瘩成纤维细胞后,观察加入10 ng/mL剂量的转化生长因子(TCF-β1)刺激前后胶原蛋白水平的变化.结果 转染小干扰RNA质粒后,胶原蛋白分泌水平降为正常表达的51.6%;经TGF-β1刺激后,蛋白表达仍无明显变化.结论 小干扰RNA质粒表达载体可抑制瘢痕疙瘩成纤维细胞胶原蛋白分泌,为临床上瘢痕疙瘩的基因治疗提供理论依据.     

敲低金属蛋白酶组织抑制物1(TIMP-1)抑制TGF-β1诱导的MRC-5人胚肺成纤维细胞增殖和胶原蛋白合成

目的探讨敲低金属蛋白酶组织抑制物1(TIMP-1)对转化生长因子β1(TGF-β1)诱导的MRC-5人胚肺成纤维细胞生长的影响。方法将MRC-5细胞分为空白组、 TGF-β1组、转染阴性对照小干涉RNA的TGF-β1组和转染TIMP-1小干涉RNA(siTIMP-1)的TGF-β1组。噻唑蓝(MTT)法检测细胞活力,流式细胞术检测细胞周期分布, ELISA检测上清液肿瘤坏死因子α(TNF-α)含量, Western blot法检测TIMP-1、α平滑肌肌动蛋白(α-SMA)、 1型胶原蛋白(Col1)和β联蛋白(β-catenin)的蛋白水平。结果转染siTIMP-1组的MRC-5细胞TIMP-1蛋白水平明显降低。与空白组相比, TGF-β1组细胞活力明显升高、 G0/G1期细胞百分比明显降低、 S期和G2/M期细胞百分比明显升高, TNF-α含量明显升高,α-SMA、 Col1和β-catenin的蛋白水平均明显升高。与TGF-β1组相比,敲低TIMP-1水平后,细胞活力明显降低、 G0/G1期细胞百分比明显升高、 S期和G2/M期细胞百分比明显降低, TNF-α含量明显降低,α-SMA、 Col1和β-catenin蛋白表达均明显降低。转染阴性对照小干涉RNA的细胞与TGF-β1组各项指标均无明显差异。结论敲低TIMP-1水平可抑制MRC-5细胞增殖活性、减少胶原蛋白合成及TNF-α释放,可能与抑制Wnt/β-catenin信号通路有关。     

重组结缔组织生长因子对大鼠血管外膜成纤维细胞表型转化的影响

目的:克隆和构建带大鼠结缔组织生长因子(CTGF)基因真核表达载体pcDNA3.1(+)/CTGF,并观察其对血管外膜成纤维细胞(AF)表型的影响。 方法:以AF总RNA为模板，进行逆转录-聚合酶链反应(RT-PCR)，获得CTGF的cDNA，克隆入pcDNA3.1(+)载体，酶切和测序鉴定重组子。将构建好的pcDNA3.1(+)/CTGF用脂质体法转入AF细胞。Western blotting观察CTGF的表达。同时观察转染pcDNA3.1(+)/CTGF对细胞表型的影响。 结果:成功构建大鼠CTGF基因的真核表达载体pcDNA3.1(+)/CTGF．并证明其能在真核细胞内表达。转染pcDNA3.1(+)/CTGF可以诱导AF表型转化。 结论:重组结缔组织生长因子可诱导大鼠血管外膜成纤维细胞表型转化。     

锌指蛋白基因抑制人平滑肌细胞表型转化的实验研究

目的探讨锌指蛋白基因A20抑制氧化型低密度脂蛋白诱导平滑肌细胞增殖及表型转化的影响。方法用DOTAP脂质体转染pEGFPEHA20-N1原代培养的平滑肌细胞,经G418筛选,A20表达经免疫荧光鉴定。Brdu检测转染前后氧化型低密度脂蛋白诱导平滑肌细胞增殖情况及α-SM-actin抗体检测细胞表型转化情况。结果 A20基因在平滑肌细胞得到有效表达,少量的氧化型低密度脂蛋白能诱导平滑肌细胞增殖,平滑肌细胞α-SM-actin骨架蛋白表达减少,而A20转染的平滑肌细胞增殖不明显,α-SM-actin骨架蛋白表达呈强阳性。结论 A20基因在动脉粥样硬化中能抑制平滑肌细胞的病理性增生。     

牛磺熊去氧胆酸减轻TGF-β1诱导的MRC-5纤维化表型

目的 研究牛磺熊去氧胆酸(TUDCA)对肺纤维化防治作用.方法 建立转化生长因子-β1(TGF-β1)诱导的人胚肺成纤维细胞(MRC-5)肺纤维化细胞模型.用MTS法测定TUDCA的安全实验剂量后,用实时定量-PCR和Western blot检测α-平滑肌动蛋白(α-SMA)和纤连蛋白的mRNA和蛋白表达.结果 1)TUDCA对MRC-5细胞无明显细胞毒作用.2)TUDCA显著缓解TGF-β1诱导的α-SMA和纤连蛋白的表达.结论 TUDCA可以缓解TGF-β1诱导的肺纤维化表型.     

大黄素抑制肺成纤维细胞增殖及转分化和胶原蛋白合成

目的探讨大黄素对肺成纤维细胞增殖、向肌纤维母细胞转化、胶原合成的影响及相关机制。方法用二甲基亚砜(DMSO)和(0、10、20、40、80、160)μmol/L大黄素处理MRC-5人胚肺成纤维细胞24、48、72 h,采用MTT法检测细胞增殖。根据细胞增殖实验结果,以DMSO及(40、80)μmol/L大黄素分别培养MRC-5细胞48 h后,采用荧光实时定量PCR检测α平滑肌肌动蛋白(α-SMA)、转化生长因子β1(TGF-β1)、含1型血小板结合蛋白基序的去整合素样金属蛋白酶1(ADAMTS-1)、1型胶原蛋白(Col1)、Col3 mRNA表达水平;Western blot法检测上述分子的蛋白水平。结果 MRC-5细胞增殖抑制率随着大黄素浓度的增加和处理时间的延长而逐渐增高。在处理48 h后,与对照组相比,(40、80)μmol/L大黄素处理组α-SMA、TGF-β1、Col1、Col3 mRNA与蛋白表达水平均降低,而ADAMTS-1 mRNA与蛋白水平升高;与40μmol/L大黄素处理组比较,80μmol/L大黄素处理组α-SMA、TGF-β1、Col1、Col3 mRNA与蛋白表达进一步下调,ADAMTS-1 mRNA与蛋白表达进一步上调。结论大黄素可抑制肺成纤维细胞增殖及其向肌纤维母细胞转化,并通过抑制TGF-β1/ADAMTS-1信号通路减少Col1、Col3合成。     

TGF-β1 shRNA真核表达质粒抑制人肺成纤维细胞TGF-β1的表达

目的:观察构建成功的三个针对人转化生长因子β1(TGF-β1)的小发夹RNA(shRNA)真核表达质粒抑制人肺成纤维细胞TGF-β1的表达.方法:将真核表达载体psiSTRIKE-RNAi1、psiSTRIKE-RNAi2、psiSTRIKE-RNAi3和对应的阴性对照载体经酶切鉴定和测序分析后,以Lipofectamine2000介导转染人肺成纤维细胞,48小时后应用实时荧光定量PCR检测人肺成纤维细胞TGF-β1 mRNA的表达并用ELISA检测细胞上清液中TGF-β1蛋白质的浓度.结果:重组质粒经酶切和DNA测序证实插入片段的碱基序列与预期设计一致.转染组细胞TGF-β1表达受到明显抑制,以psiSTRIKE-RNAi2的抑制效应最为显著(P＜0.01).结论:三个针对TGF-β1shRNA的重组质粒均能抑制TGF-β1在人肺成纤维细胞中的表达.     

RNAi沉默HIF-10α基因抑制滋养细胞TGF-3β表达的实验研究

目的 构建缺氧诱导因子1α(hypoxia-inducible factor 1α,HIF-1α)基因的短发夹状干扰RNA(short hairpin RNA,shRNA)表达质粒,探讨其在低氧条件下对BeWo细胞转化生长因子3β(transforming growth factor 3β,TGF-3β)基因表达的抑制作用.方法 根据小干扰RNA(small interference RNA,siRNA)设计原则,针对HIF-1α基因设计并合成两条寡聚DNA片段,退火后克隆入pSilencer2.1-U6-neo质粒,应用脂质体将重组质粒转染BeWo细胞.缺氧培养后,应用Western blot法检测滋养细胞HIF-1α和TGF-3β蛋白表达水平,应用real time PCR法检测滋养细胞HIF-1α和TGF-3βmRNA表达水平.结果 成功构建HIF-1α的shRNA真核表达载体,转染BeWo细胞.低氧条件下,细胞HIF-1α蛋白和mRNA表达下降;同时细胞TGF-3β蛋白和mRNA表达也降低.结论 构建的HIF-1α基因shRNA表达质粒在低氧条件下明显抑制滋养细胞TGF-3β基因的表达.     

TGF-β1诱导成肌纤维细胞形成在低氧性

目的探讨转化生长因子-β1(TGF-β1)诱导成肌纤维细胞形成在低氧性肺血管重塑中的作用。方法40只成年雄性Wistar大鼠随机分成:对照组、低氧3、7、14和21 d组,每组8只,测大鼠平均肺动脉压(mPAP)、血管形态学指标、右室肥大指数(RVHI);免疫组化检测α-平滑肌肌动蛋白(α-SMA)的表达,原位杂交和免疫组化检测TGF-β1基因表达,透射电镜观察腺泡内血管壁细胞表型,细胞培养观察低氧和TGF-β1诱导人胚肺成纤维细胞是否发生表型转化。结果(1)低氧7 d后大鼠mPAP升高(P<0.05)。低氧14 d后出现肺血管重塑、右心室肥大。(2)从低氧7 d开始无肌型动脉、部分肌型动脉、肌型动脉的构成比分别是39%、46%和15%,与对照组60%、35%和5%比较差异显著(P<0.005)。(3)腺泡内肺动脉管壁α-SMA的表达随着低氧时间的延长逐渐增多。低氧14 dTGF-β1mRNA表达增高(P<0.01);TGF-β1蛋白在对照组呈弱阳性,低氧3 d表达增强(P<0.01),低氧7 d达高峰(P<0.01)。(4)透射电镜证实成肌纤维细胞含有特异性的微丝和丰富的粗面内质网。(5)细胞培养表明低氧能够刺激成纤维细胞发生表型转化,TGF-β1能够促进成纤维细胞表型转化的发生。结论转化生长因子β1诱导成肌纤维细胞形成是低氧性肺血管重塑的重要原因之一。     

人胎盘间充质干细胞调控TGF-β1/Smad3信号通路抑制肺纤维化的发生

背景：研究表明人胎盘间充质干细胞能有效抑制肺纤维化的发展,但其发挥作用的具体机制目前并不清楚。目的：探究人胎盘间充质干细胞对二氧化硅诱导人胚肺成纤维细胞发生肺纤维化的治疗作用及相关机制。方法：CCK-8法检测不同质量浓度二氧化硅干预不同时间对MRC-5细胞增殖活力的影响,结合免疫荧光染色法筛选出最佳的二氧化硅刺激质量浓度与时间用于后续实验。将MRC-5细胞分为空白组、二氧化硅组、二氧化硅+人胎盘间充质干细胞组,空白组细胞不予任何处理,二氧化硅组MRC-5细胞给予100μg/mL二氧化硅刺激48 h,二氧化硅+人胎盘间充质干细胞组MRC-5细胞先给予100μg/mL二氧化硅刺激48 h后再与人胎盘间充质干细胞共培养24 h。免疫荧光染色检测各组细胞α-平滑肌肌动蛋白、胶原蛋白Ⅰ型蛋白的表达;Western blot检测各组细胞肺纤维化相关蛋白和TGF-β1/Smad 3信号通路相关蛋白表达。结果与结论：(1)CCK-8结果显示,100μg/mL二氧化硅刺激MRC-5细胞48 h为最佳质量浓度与时间;(2)免疫荧光染色结果显示,与二氧化硅组相比,二氧化硅+人胎盘间充质干细胞组α-平滑肌肌动...     

Inhibition of activin receptor-like kinase 5 attenuates bleomycin-induced pulmonary fibrosis

Activin receptor-like kinase 5 (ALK5) is a type I receptor of transforming growth factor (TGF)-beta. ALK5 inhibition has been reported to attenuate the tissue fibrosis including pulmonary fibrosis, renal fibrosis and liver fibrosis. To elucidate the inhibitory mechanism of ALK5 inhibitor on pulmonary fibrosis in vivo, we performed the histopathological assessment, gene expression analysis of extracellular matrix (ECM) genes and immunohistochemistry including receptor-activated Smads (R-Smads; Smad2/3), CTGF, myofibroblast marker (alpha-smooth muscle actin; aSMA) and type I collagen deposition in the lung using Bleomycin (BLM)-induced pulmonary fibrosis model. ALK5 inhibitor, SB-525334 (10 mg/kg or 30 mg/kg) was orally administered at twice a day. Lungs were isolated 5, 7, 9 and 14 days after BLM treatment. BLM treatment led to significant pulmonary fibrotic changes accompanied by significant upregulation of ECM mRNA expressions, Smad2/3 nuclear translocation, CTGF expression, myofibroblast proliferation and type I collagen deposition. SB-525334 treatment attenuated the histopathological alterations in the lung, and significantly decreased the type I and III procollagen and fibronectin mRNA expression. Immunohistochemistry revealed that SB-525334 treatment showed significant attenuation in Smad2/3 nuclear translocation, decrease in CTGF-expressing cells, myofibroblast proliferation and type I collagen deposition. These results suggest that ALK5 inhibition attenuates R-Smads activation thereby attenuates pulmonary fibrosis.     

MUC4 is overexpressed in idiopathic pulmonary fibrosis and collaborates with transforming growth factor β inducing fibrotic responses

Several mucins are implicated in idiopathic pulmonary fibrosis (IPF); however, there is no evidence regarding the role of MUC4 in the development of IPF. Here we demonstrated that MUC4 was overexpressed in IPF patients (n = 22) compared with healthy subjects (n = 21) and located in pulmonary arteries, bronchial epithelial cells, fibroblasts, and hyperplastic alveolar type II cells. Decreased expression of MUC4 using siRNA–MUC4 inhibited the mesenchymal/myofibroblast transformations of alveolar type II A549 cells and lung fibroblasts, as well as cell senescence and fibroblast proliferation induced by TGF-β1. The induction of the overexpression of MUC4 increased the effects of TGF-β1 on mesenchymal/myofibroblast transformations and cell senescence. MUC4 overexpression and siRNA–MUC4 gene silencing increased or decreased, respectively, the phosphorylation of TGFβRI and SMAD3, contributing to smad-binding element activation. Immunoprecipitation analysis and confocal immunofluorescence showed the formation of a protein complex between MUC4β/p-TGFβRI and p-SMAD3 in the cell membrane after TGF-β1 stimulation and in lung tissue from IPF patients. Bleomycin-induced lung fibrosis was reduced in mice transiently transfected with siRNA–MUC4. This study shows that MUC4 expression is enhanced in IPF and promotes fibrotic processes in collaboration with TGF-β1 canonical pathway that could be an attractive druggable target for human IPF.     

Simvastatin inhibits growth factor expression and modulates profibrogenic markers in lung fibroblasts

Simvastatin is best known for its antilipidemic action and use in cardiovascular disease due to its inhibition of 3-hydroxy-3-methylglutaryl CoenzymeA (HMG CoA) reductase, a key enzyme in the cholesterol synthesis pathway. Inhibition of biological precursors in this pathway also enables pleiotrophic immunomodulatory and anti-inflammatory capabilities, including modulation of growth factor expression. Connective tissue growth factor (CTGF) and persistent myofibroblast formation are major determinants of the aggressive fibrotic disease, idiopathic pulmonary fibrosis (IPF). In this study we used human lung fibroblasts derived from healthy and IPF lungs to examine Simvastatin effects on CTGF gene and protein expression, analyzed by RT-PCR and ELISA, respectively. Simvastatin significantly inhibited (P < 0.05) CTGF gene and protein expression, overriding the induction by transforming growth factor-beta1, a known potent inducer of CTGF. Such Simvastatin suppressor action on growth factor interaction was reflected functionally on recognized phenotypes of fibrosis. alpha-smooth muscle actin expression was downregulated and collagen gel contraction reduced by 4.94- and 7.58-fold in IMR90 and HIPF lung fibroblasts, respectively, when preconditioned with 10 microM Simvastatin compared with transforming growth factor-beta1 treatment alone after 24 h. Our data suggest that Simvastatin can modify critical determinants of the profibrogenic machinery responsible for the aggressive clinical profile of IPF, and potentially prevents adverse lung parenchymal remodeling associated with persistent myofibroblast formation.     

Loss of fibroblast Thy-1 expression correlates with lung fibrogenesis

Fibroblasts consist of heterogeneous subpopulations that have distinct roles in fibrotic responses. Previously we reported enhanced proliferation in response to fibrogenic growth factors and selective activation of latent transforming growth factor (TGF)-beta in fibroblasts lacking cell surface expression of Thy-1 glycoprotein, suggesting that Thy-1 modulates the fibrogenic potential of fibroblasts. Here we report that compared to controls Thy-1-/- C57BL/6 mice displayed more severe histopathological lung fibrosis, greater accumulation of lung collagen, and increased TGF-beta activation in the lungs 14 days after intratracheal bleomycin. The majority of cells demonstrating TGF-beta activation and myofibroblast differentiation in bleomycin-induced lesions were Thy-1-negative. Histological sections from patients with idiopathic pulmonary fibrosis demonstrated absent Thy-1 staining within fibroblastic foci. Normal lung fibroblasts, in both mice and humans, were predominantly Thy-1-positive. The fibrogenic cytokines interleukin-1 and tumor necrosis factor-alpha induced loss of fibroblast Thy-1 surface expression in vitro, which was associated with Thy-1 shedding, Smad phosphorylation, and myofibroblast differentiation. These results suggest that fibrogenic injury promotes loss of lung fibroblast Thy-1 expression, resulting in enhanced fibrogenesis.     

Periostin regulates fibrocyte function to promote myofibroblast differentiation and lung fibrosis

Fibrocytes are circulating mesenchymal precursors (CD45+, col 1+) recruited to fibrotic areas. Fibrocytes secrete profibrotic mediators including periostin; a matricellular protein that regulates cellular interactions with extracellular matrix (ECM) components. In bleomycin-induced fibrosis, periostin deficiency in structural or hematopoietic cells limits development of pulmonary fibrosis. To determine if hematopoietic-derived fibrocytes might secrete soluble factors to activate structural myofibroblast differentiation, wild-type (WT) fibroblasts were treated with conditioned medium from fibrocytes isolated from bleomycin-treated WT or periostin^−/− mice. After 24 h we saw less α-smooth muscle actin expression in cells treated with conditioned medium from periostin^−/− fibrocytes. Adoptive transfer of WT fibrocytes augmented lung fibrosis to a greater extent than transfer of fibrocytes from periostin^−/− mice. In vitro analysis of fibrocytes and fibroblasts isolated from WT and periostin^−/− mice treated with TGFβ1 or periostin demonstrated co-regulation of mesenchymal activation and beta 1 integrin as a potential receptor for periostin on fibrocytes. Additionally, connective tissue growth factor (CTGF) mRNA expression was increased in fibrocytes treated with periostin whereas CTGF and lysl oxidase (LOX) mRNA expression was low in bleomycin-treated periostin^−/− fibrocytes. These data suggest fibrocytes may augment bleomycin-induced fibrosis via secretion of periostin and other soluble factors that promote myofibroblast differentiation.     

Lack of MK2 inhibits myofibroblast formation and exacerbates pulmonary fibrosis

Fibroblasts play a major role in tissue repair and remodeling. Their differentiation into myofibroblasts, marked by increased expression of smooth muscle-specific alpha-actin (alpha-SMA), is believed to be important in wound healing and fibrosis. We have recently described a role for MK2 in this phenotypic differentiation in culture. In this article, we demonstrate that MK2 also regulates myofibroblasts in vivo. Disruption of MK2 in mice prevented myofibroblast formation in a model of pulmonary fibrosis. However, MK2 disruption and consequent lack of myofibroblast formation exacerbated fibrosis rather than ameliorated it as previously postulated. When mice lacking MK2 (MK2-/-) were exposed to bleomycin, more collagen accumulated and more fibroblasts populated fibrotic regions in their lungs than in similarly treated wild-type mice. While there were many vimentin-positive cells in the bleomycin-treated MK2-/- mouse lungs, few alpha-SMA-positive cells were observed in these lungs compared with wild-type mouse lungs. siRNA against MK2 reduced alpha-SMA expression in wild-type mouse embryonic fibroblasts (MEF), consistent with its suppression in MK2-/- MEF. On the other hand expressing constitutively active MK2 in MK2-/- MEF significantly increased alpha-SMA expression. MK2-/-MEF proliferated at a faster rate and produced more collagen; however, they migrated at a slower rate than wild-type MEF. Overexpressing phosphomimicking HSP27, a target of MK2, did not reverse the effect of MK2 disruption on fibroblast migration. MK2 disruption did not affect Smad2 activation by transforming growth factor-beta. Thus, MK2 appears to mediate myofibroblast differentiation, and inhibiting that differentiation might contribute to fibrosis rather than protect against it.     

TNF-alpha sensitizes normal and fibrotic human lung fibroblasts to Fas-induced apoptosis

Pulmonary accumulation of fibroblasts and myofibroblasts in idiopathic pulmonary fibrosis/usual interstitial pneumonia (IFP/UIP) has been linked to (1) increased migration of a circulating pool of fibrocytes, (2) cell proliferation, and (3) resistance to apoptosis. The mechanism of physiologic apoptosis of lung fibroblasts is poorly understood. Using normal and fibrotic human lung fibroblasts and the human lung fibroblast cell line, MRC-5, we examined the regulation of Fas-induced apoptosis by the proinflammatory cytokines TNF-alpha and IFN-gamma. Herein, we show that the basal resistance of lung fibroblasts and myofibroblasts to Fas-induced apoptosis is overcome by sensitization with TNF-alpha. IFN-gamma did not sensitize cells to Fas-induced apoptosis, but exhibited synergistic activity with TNF-alpha. Sensitization by TNF-alpha was observed in MRC-5 cells and in fibroblasts and myofibroblasts from normal and fibrotic human lung, suggesting that this represents a conserved mechanism to engage Fas-induced apoptosis. The mechanism of sensitization was localized at the level of recruitment of the adapter protein, FADD, to the cytoplasmic domain of Fas. Collectively, these findings suggest that fibroblast apoptosis involves two steps, sensitization and induction, and that inadequate pulmonary inflammation in IPF/UIP may favor fibroblast accumulation by reducing sensitization to apoptosis.     

Enhanced myofibroblastic differentiation and survival in Thy-1(-) lung fibroblasts

Thy-1 is a glycosylphosphatidyl-inositol-linked cell surface glycoprotein whose exact biological role remains unclear. Differential expression of Thy-1 affects fibroblast proliferation and fibrogenic signaling. In idiopathic pulmonary fibrosis, the proliferating myofibroblasts within the fibroblastic foci are Thy-1(-), whereas normal lung fibroblasts are predominantly Thy-1(+). In this study, we used rat lung fibroblasts sorted for Thy-1 expression to examine myofibroblastic differentiation in response to fibrogenic stimuli. We examined the effects of transforming growth factor-beta, endothelin-1, and connective tissue growth factor on the expression of myofibroblast proteins and myogenic regulatory factors by real-time RT-PCR and immunoblotting. Thy-1(-) cells have significantly higher myofibroblast and myogenic regulatory factor gene and protein expression compared with Thy-1(+) cells, confirmed by immunofluorescence. We also used floating collagen matrix contraction assays to assess the functional differentiation of the fibroblasts. At baseline and after stimulation with transforming growth factor-beta and endothelin-1, Thy-1(-) cells caused significantly greater collagen contraction than did Thy-1(+) cells, supporting the hypothesis that Thy-1(-) cells are more fully differentiated myofibroblasts. Because apoptosis has been implicated in the regression of myofibroblasts, we examined the percentage of apoptotic cells in the contracted collagen matrices at baseline and after stimulation with fibrogenic agents. A significantly greater proportion of Thy-1(+) cells underwent apoptosis in all conditions compared with Thy-1(-) fibroblasts. Transfection of Thy-1 into Thy-1(-) cells inhibits collagen matrix contraction and reduces cell survival. Our data indicate that Thy-1 regulates myogenic gene expression, myofibroblastic differentiation, and survival in lung fibroblasts.     

端粒 端粒酶与特发性肺间质纤维化

特发性肺纤维化(idiopathic pulmonary fibrosis, IPF) 是一种病因不明、发病机制不清、缺乏有效治疗手段的弥漫性肺间质疾病,其病理特征是肺泡上皮损伤、成纤维细胞灶(fibroblast foci) 的形成以及细胞外基质的过度积聚,最终导致了肺泡结构的异常重塑[1,2].