日本血吸虫重组半胱氨酸蛋白酶抑制剂对小鼠心肌梗死预后的影响及其免疫调节机制

目的 探讨日本血吸虫重组半胱氨酸蛋白酶抑制剂(rSjcystatin)对小鼠心肌梗死(myocardial infarction,MI)预后的影响及其免疫调节机制.方法 建立小鼠MI模型,分别于术后1、3、5、7、14、28 d经腹腔注射PBS及10、25 μg rSjcystatin.术后28 d,记录MI小鼠的生存...     

木蝴蝶总黄酮对小鼠实验性急性心肌梗死的保护作用

研究了木蝴蝶总黄酮对小鼠实验性心肌梗死的保护作用。通过开胸结扎左冠状动脉前降支(LAD)建立小鼠急性心肌梗死模型。观察木蝴蝶总黄酮对实验性心肌梗死的影响,并从生化学角度探讨其作用机制。结果表明:腹腔注射木蝴蝶总黄酮2 mg/g,4 mg/g和8 mg/g。对急性心肌梗死24 h的小鼠,可明显降低血清磷酸肌酸激酶(CPK)、乳酸脱氢酶(LDH)活性及脂质过氧化物(LPO)的含量,提高超氧化物转化酶(SOD)活性;从而缩小急性心肌梗死的面积(MIS)。TFO能明显降低小鼠心肌耗氧量,保护缺氧心肌,延长小鼠存活时间具有一定的作用。     

肺炎链球菌dnaJ基因缺陷对小鼠肺炎感染模型天然免疫应答的影响

目的探讨肺炎链球菌(Streptococcus pneumonia,S.pn)dnaJ基因缺陷对肺炎感染模型小鼠天然免疫应答的影响。方法将BALB/c小鼠随机分为空白对照组、D39感染组和△dnaJ感染组,分别经鼻腔滴注30μl无菌PBS、30μl含2×107cfu的S.pn D39和△dnaJ(dnaJ基因缺陷株)菌液,复制小鼠肺炎感染模型。于感染后6、12、24、36和48 h处死小鼠,取肺组织,匀浆后分离上清,ELISA检测促炎因子TNF-α、IL-1β、IL-6和IFNγ的表达水平,HE染色观察感染12 h的小鼠肺组织炎症反应变化;将小鼠巨噬细胞株RAW264.7体外感染S.pn D39和△dnaJ,细菌与细胞的比例为100∶1,感染1、2、3 h后分离细胞培养上清液,ELISA检测TNF-α和IL-6的表达水平。实时定量PCR和Western blot分别检测感染12 h的小鼠肺组织中模式识别受体TLRs基因mRNA的转录水平和炎症相关信号p38MAPK的磷酸化水平。结果与D39感染组相比,△dnaJ感染组小鼠肺组织炎症反应强度下降,TNF-α、IL-6和IL-1β等促炎因子水平达峰时间延迟,且峰值降低,RAW264.7细胞感染3 h分泌TNF-α和IL-6显著减少(P<0.01或P<0.05);小鼠肺组织Tlr2和Tlr13基因mRNA转录水平显著降低(P<0.05),p38MAPK的磷酸化水平也明显下降。结论肺炎链球菌dnaJ基因缺陷可下调肺炎感染模型小鼠的炎症反应、促炎因子分泌及胞内信号分子的激活,也可影响小鼠感染后肺组织中Trl2和Tlr13基因mRNA的表达,为进一步研究机体对肺炎链球菌DnaJ蛋白的天然免疫应答分子机制奠定了基础。     

姜黄素对小鼠心肌缺血再灌注损伤的保护作用及其与Toll样受体4/核因子-κB信号通路的相关性

目的探讨姜黄素对小鼠心肌缺血再灌注损伤(myocardial ischemia-reperfusion injury,MIRI)的保护作用及其与Toll样受体4(Toll-like receptor 4,TLR4)/核因子-κB(nuclear factor kappa-light-chain-enhancer of activated B cells,NF-κB)信号通路的相关性。方法取健康C57BL/6小鼠,采用随机区组法分为假手术组(Sham组)、MIRI组及姜黄素预处理的MIRI组(Cur组):使用丝线暂时阻断小鼠冠状动脉前降支(left anterior descending,LAD)血流30 min,再灌注4 h,建立小鼠MIRI模型;假手术组接受相同的手术过程,但未阻断LAD;Cur组在缺血前30 min腹腔注射姜黄素(100 mg/kg)。采用伊文思蓝和氯化三苯基四氮唑(2,3,5-triphenyltetrazolium chloride,TTC)染色评估小鼠心肌梗死面积;电化学发光法检测小鼠血清肌钙蛋白(cardiac troponin T,cTnT)水平;RT-PCR法检测小鼠心肌组织TLR4及肿瘤坏死因子-α(tumor nectosis factor-alpha,TNF-α,)mRNA水平;Western blot法检测小鼠心肌组织NF-κB蛋白表达水平;ELISA法检测小鼠心肌组织TNF-α蛋白表达水平。结果 Cur组小鼠心肌梗死面积及血清cTnT均低于MIRI组(P均0.01);Cur组小鼠心肌组织TLR4、TNF-αm RNA水平及NF-κB、TNF-α蛋白表达水平均低于MIRI组(P均0.05)。结论姜黄素对小鼠MIRI的心肌具有保护作用,可能是通过TLR4/NF-κB信号通路实现的。     

小鼠Sca-1^+干细胞对心肌梗死模型小鼠的疗效及其基因调控机制

目的探讨小鼠干细胞抗原-1阳性(stem cell antigen-1-positive,Sca-1^+)干细胞(stem cells,SCs)对心肌梗死(myocardial infarction,MI)模型小鼠的疗效及其基因调控机制。方法采用免疫磁珠分选法急性分离2日龄及3、6、9、12月龄小鼠心脏Sca-1^+SCs;通过结扎8周龄小鼠心脏冠状动脉左主降支,建立小鼠急性MI模型,于心梗边缘区分别注射PBS和Sca-1^+SCs悬液。术后行超声心动图测定心功能,Masson三色染色、心重/体重比(HW/BW)用于评价各组Sca-1^+SCs对心脏结构的影响。将各组小鼠心脏Sca-1^+SCs进行全基因组测序,通过STEM软件对转录组基因表达水平进行聚类及GO富集分析,筛选出乳鼠和成年鼠差异表达的基因类型,并采用qRT-PCR法进一步验证目的基因的表达情况。结果 MI术后,与PBS组比较,乳鼠心脏Sca-1^+SCs治疗组小鼠左室射血分数(left ventricular ejection fraction,LVEF)和左室短轴缩短率(left ventricular fraction shortening,LVFS)均明显升高(P <0. 05),HW/BW明显降低(P <0. 05),左室舒张末内径(left ventricular diastolic internal diameter,LVIDd)明显减小(P <0. 05);与成年鼠比较,乳鼠心脏Sca-1^+SCs移植治疗可降低心肌梗死面积,缓解心腔扩大。在乳鼠心脏Sca-1^+SCs中高表达,而成年鼠表达降低的基因共185个,regulation of developmental process条目上富集基因有38个,其中肌球蛋白重链6(myosin heavy chain6 cardiac muscle alpha,Myh6)、胰岛素样生长因子2(insulin-like growth factor 2,Igf2)、成骨细胞特异性因子(periostin,Postn)、神经元再生相关蛋白(neuronal regeneration related protein,Nrep)基因在乳鼠心脏Sca-1^+SCs中具有较高转录水平。与乳鼠比较,成年小鼠心脏Sca-1^+SCs中Myh6、Igf2、Postn、Nrep基因m RNA的表达水平均显著下调(P <0. 05)。结论乳鼠心脏Sca-1^+SCs移植对MI的疗效优于成年小鼠,其原因可能是乳鼠心脏Sca-1^+SCs中Myh6、Igf2、Postn、Nrep等基因的表达水平高于成年小鼠。     

小鼠多能干细胞对小鼠肝脏电离辐射损伤的作用

目的探讨小鼠多能干细胞(mouse pluripotent stem cells,miPS)对小鼠肝脏电离辐射损伤的作用。方法采用医用电子直线加速器进行单次全身性照射(电子辐射线源为6 MeV,照射总剂量为8 Gy,照射剂量率为1. 0 Gy/min)。辐射组于辐射后12和24 h,经小鼠尾静脉注射生理盐水(200μL/只);治疗组于照射后12和24 h,经尾静脉注射mi PS细胞悬浮液[3×106个/(200μL·只)];对照组小鼠不进行辐射,仅注射生理盐水(200μL/只)。末次注射后1、3、7、14 d,记录小鼠体重、计算肝脏指数,并检测小鼠肝脏中超氧化物歧化酶(superoxide dismutase,SOD)及丙二醛(malondialdehyde,MDA)水平;末次注射后14 d,观察小鼠状态,并采用组织病理学方法观察肝脏病理形态学变化。结果与对照组比较,辐射组小鼠精神状态和食欲状况均不佳,体重显著降低(P <0. 05),肝脏指数差异无统计学意义(P> 0. 05),肝脏中SOD活性显著降低(P <0. 01),MDA水平显著升高(P <0. 05);与辐射组比较,治疗组小鼠体重明显升高(P <0. 05),肝脏指数差异无统计学意义(P> 0. 05),肝脏中SOD活性显著升高(P <0. 05),MDA水平显著降低(P <0. 01)。对照组小鼠肝脏组织无明显病变;辐射组小鼠肝细胞发生明显肿胀及肝细胞索紊乱等明显病理变化;治疗组小鼠肝细胞索排列整齐,肝细胞轻度肿胀,病理变化得到改善。结论 miPS可通过其增殖分化减少小鼠体内氧化应激产生的细胞凋亡,对电离辐射造成的小鼠肝脏损害有明显的修复作用。     

静脉注射美托洛尔对急性心肌梗死38例临床分析

目的研究静脉注射美托洛尔对急性心肌梗死早期治疗效果。方法 40例心肌梗死患者,美托洛尔0.1mg/kg用5%葡萄糖盐水稀释成20mL在5min内静注,在给药前及给药后纪录心电图、血压、心肺体征及临床表现的观察。结果治疗组静注美托洛尔后病人心律失常消失或明显减少,其临床心悸不适症状逐渐消失,无心衰及心律失常加重死亡。对照组病人内无改善改用常规方案处理。结论美托洛尔疗效确切,可使心肌耗氧量降低,改善缺血区的氧供需失衡,缩小心肌梗死面积,限制梗死面积扩展,降低急性期病死率有肯定疗效。     

治疗用卡介苗在膀胱癌预防及治疗中的作用

目的探讨治疗用卡介苗(Bacillus Calmette-Guerin vaccine for treatment,BCGt)在膀胱癌预防及治疗中的作用。方法 MB49细胞灌注小鼠膀胱,建立小鼠原位膀胱癌模型,进行BCGt预防性和治疗性试验,观察小鼠生存情况。末次治疗后第6天,经小鼠眼球采血,检测血清中IgG、IFNγ和IL-6的含量,同时取小鼠脾脏,检测特异性T淋巴细胞;每次治疗后检测小鼠尿液中一氧化氮(NO)含量;末次治疗45 d后进行记忆性免疫试验。结果成功建立了基于MB49细胞的小鼠原位肿瘤模型,致癌率100%。BCGt免疫预防和治疗两种方式均可延长小鼠的生存期;BCGt治疗后小鼠血清中的IgG、IFNγ、IL-6及尿液中NO含量明显升高(P 0. 05),特异性T淋巴细胞反应明显增强(P 0. 001),且可产生免疫记忆。结论 BCGt具有预防及治疗膀胱癌的作用,且BCGt抗肿瘤作用可能是通过产生IFNγ、IL-6、NO等发挥作用的。     

快中子辐照直拉硅中的空位型缺陷

利用正电子湮没谱(PAS)及Fourier变换红外吸收光谱(FTIR)技术研究了快中子辐照直拉硅(CZSi)中辐照缺陷.研究发现,经快中子辐照后的硅中会有大量的单空位型缺陷VO及多空位型缺陷V2和V2O;经200～450℃热处理后,FTIR光谱中出现的720和919.6 cm-1红外吸收峰为单空位型缺陷,其正电子寿命与VO的寿命接近,约为290 ps;经450～600℃热处理后,随单空位型缺陷VO消失,V4型缺陷浓度迅速增加,600℃热处理后其浓度达到最大(相对浓度约为70％).     

低剂量蓖麻毒素吸入诱导的小鼠肺损伤及修复

目的分析雾化吸入低剂量蓖麻毒素(ricin toxin,RT)对小鼠肺组织损伤修复的影响。方法采用改良寇氏法检测小鼠雾化吸入不同剂量RT(1. 312、2. 2、3. 704、6. 2、10. 44μg/kg)的LC_(50),确定RT雾化染毒剂量。小鼠雾化吸入1/30 LC_(50)剂量RT后,分别在第0. 5、1、2、3、4、5、6、7天,分离肺组织,HE染色观察小鼠肺组织病理学变化,免疫组化方法检测肺组织中MMP-2和MMP-9蛋白的表达。结果小鼠雾化吸入RT的LC_(50)为(4. 95±0. 14)μg/kg;雾化染毒后,小鼠肺组织损伤程度及MMP-2、MMP-9蛋白的表达趋势一致。第1、2天时,肺组织血管周围弥漫性水肿,MMP-2、MMP-9蛋白的表达高于空白对照组,差异有统计学意义(P 0. 05);第3、4天时,肺泡结构完全破坏,第3天MMP-2蛋白的表达达到最高,与空白对照组相比,差异有统计学意义(P 0. 01),第4天MMP-9蛋白的表达达到最高,与空白对照组相比,差异有统计学意义(P 0. 01);至第7天时,肺损伤程度基本恢复至正常状态,MMP-2、MMP-9蛋白的表达也呈下降趋势。结论雾化吸入1/30 LC_(50)剂量RT后,可引起小鼠肺组织损伤,且损伤可在7 d内修复。     

Metformin Attenuates Postinfarction Myocardial Fibrosis and Inflammation in Mice

Diabetes is a major risk factor for the development of cardiovascular disease with a higher incidence of myocardial infarction. This study explores the role of metformin, a first-line antihyperglycemic agent, in postinfarction fibrotic and inflammatory remodeling in mice. Three-month-old C57BI/6J mice were submitted to 30 min cardiac ischemia followed by reperfusion for 14 days. Intraperitoneal treatment with metformin (5 mg/kg) was initiated 15 min after the onset of reperfusion and maintained for 14 days. Real-time PCR was used to determine the levels of COL3A1, αSMA, CD68, TNF-α and IL-6. Increased collagen deposition and infiltration of macrophages in heart tissues are associated with upregulation of the inflammation-associated genes in mice after 14 days of reperfusion. Metformin treatment markedly reduced postinfarction fibrotic remodeling and CD68-positive cell population in mice. Moreover, metformin resulted in reduced expression of COL3A1, αSMA and CD68 after 14 days of reperfusion. Taken together, these results open new perspectives for the use of metformin as a drug that counteracts adverse myocardial fibroticand inflammatory remodeling after MI.     

Aging Impairs Reverse Remodeling and Recovery of Ventricular Function after Isoproterenol-Induced Cardiomyopathy

Information about heart failure with reduced ejection fraction (HFrEF) in women and the potential effects of aging in the female heart is scarce. We investigated the vulnerability to develop HFrEF in female elderly mice compared to young animals, as well as potential differences in reverse remodeling. First, HF was induced by isoproterenol infusion (30 mg/kg/day, 28 days) in young (10-week-old) and elderly (22-month-old) female mice. In a second set of animals, mice underwent isoproterenol infusion followed by no treatment during 28 additional days. Cardiac remodeling was assessed by echocardiography, histology and gene expression of collagen-I and collagen-III. Following isoproterenol infusion, elderly mice developed similar HFrEF features compared to young animals, except for greater cell hypertrophy and tissue fibrosis. After beta-adrenergic withdrawal, young female mice experienced complete reversal of the HFrEF phenotype. Conversely, reversed remodeling was impaired in elderly animals, with no significant recovery of LV ejection fraction, cardiomyocyte hypertrophy and collagen deposition. In conclusion, chronic isoproterenol infusion is a valid HF model for elderly and young female mice and induces a similar HF phenotype in both. Elderly animals, unlike young, show impaired reverse remodeling, with persistent tissue fibrosis and cardiac dysfunction even after beta-adrenergic withdrawal.     

大剂量盐酸异丙肾上腺素诱发大鼠心肌缺血性坏死模型的建立

目的建立大剂量盐酸异丙肾上腺素(Iso)诱发大鼠心肌缺血性坏死模型。方法多点皮下注射Iso15mg/kg,建立大鼠心肌缺血坏死模型,并检测其心电图(ECG)、血清酶学指标、心肌血清羟脯氨酸含量、三磷酸腺苷(ATP)含量及HE染色结果。结果与正常对照组比较,模型组大鼠心电图各点ST段和T波均有明显的变化;注射Iso后4h,乳酸脱氢酶(LDH)、肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)水平达高峰;注射后6h,天门冬氨酸氨基转移酶(AST)水平达高峰;随着注射后时间的延长和病变程度的加重,心肌血清羟脯氨酸含量明显增加;ATP含量明显降低;注射Iso2h后,模型组即出现小的坏死灶,且随时间的延长,病变程度明显加重,坏死面积在3周达到最大,并出现明显的纤维化。结论一次性皮下多点注射15mg/kg的Iso,可成功地诱发大鼠心肌缺血性坏死,且可出现明显的纤维化。     

Structural and Functional Support by Left Atrial Appendage Transplant to the Left Ventricle after a Myocardial Infarction

The left atrial appendage (LAA) of the adult heart has been shown to contain cardiac and myeloid progenitor cells. The resident myeloid progenitor population expresses an array of pro-regenerative paracrine factors. Cardiac constructs have been shown to inhibit deleterious remodeling of the heart using physical support. Due to these aspects, LAA holds promise as a regenerative transplant. LAAs from adult mT/mG mice were transplanted to the recipient 129X1-SvJ mice simultaneously as myocardial infarction (MI) was performed. A decellularized LAA patch was implanted in the control group. Two weeks after MI, the LAA patch had integrated to the ventricular wall, and migrated cells were seen in the MI area. The cells had two main phenotypes: small F4/80+ cells and large troponin C+ cells. After follow-up at 8 weeks, the LAA patch remained viable, and the functional status of the heart improved. Cardiac echo demonstrated that, after 6 weeks, the mice in the LAA-patch-treated group showed an increasing and statistically significant improvement in cardiac performance when compared to the MI and MI + decellularized patch controls. Physical patch-support (LAA and decellularized LAA patch) had an equal effect on the inhibition of deleterious remodeling, but only the LAA patch inhibited the hypertrophic response. Our study demonstrates that the LAA transplantation has the potential for use as a treatment for myocardial infarction. This method can putatively combine cell therapy (regenerative effect) and physical support (inhibition of deleterious remodeling).     

S100A8/A9 Enhances Immunomodulatory and Tissue-Repairing Properties of Human Amniotic Mesenchymal Stem Cells in Myocardial Ischemia-Reperfusion Injury

Paracrine factors of human mesenchymal stem cells (hMSCs) have the potential of preventing adverse cardiac remodeling after myocardial infarction (MI). S100A8 and S100A9 are calcium-binding proteins playing essential roles in the regulation of inflammation and fibrous tissue formation, and they might modulate the paracrine effect of hMSCs. We isolated human amniotic mesenchymal stem cells (hAMSCs) and examined the changes in the expression level of regulatory genes of inflammation and fibrosis after hAMSCs were treated with S100A8/A9. The anti-inflammatory and anti-fibrotic effects of hAMSCs pretreated with S100A8/A9 were shown to be superior to those of hAMSCs without S100A8/A9 pretreatment in the cardiomyocyte hypoxia/reoxygenation experiment. We established a murine myocardial ischemia/reperfusion model to compare the therapeutic effects of the conditioned medium of hAMSCs with or without S100A8/A9 pretreatment. We found the hearts administered with a conditioned medium of hAMSCs with S100A8/A9 pretreatment had better left ventricular systolic function on day 7, 14, and 28 after MI. These results suggest S100A8/A9 enhances the paracrine therapeutic effects of hAMSCs in aspects of anti-inflammation, anti-fibrosis, and cardiac function preservation after MI.     

A Brief Review on the Biology and Effects of Cellular and Circulating microRNAs on Cardiac Remodeling after Infarction

Despite advances in diagnostic, prognostic, and treatment modalities, myocardial infarction (MI) remains a leading cause of morbidity and mortality. Impaired cellular signaling after an MI causes maladaptive changes resulting in cardiac remodeling. MicroRNAs (miRNAs/miR) along with other molecular components have been investigated for their involvement in cellular signaling in the pathogenesis of various cardiac conditions like MI. miRNAs are small non-coding RNAs that negatively regulate gene expression. They bind to complementary mRNAs and regulate the rate of protein synthesis by altering the stability of their targeted mRNAs. A single miRNA can modulate several cellular signaling pathways by targeting hundreds of mRNAs. This review focuses on the biogenesis and beneficial effects of cellular and circulating (exosomal) miRNAs on cardiac remodeling after an MI. Particularly, miR-1, -133, 135, and -29 that play an essential role in cardiac remodeling after an MI are described in detail. The limitations that will need to be addressed in the future for the further development of miRNA-based therapeutics for cardiovascular conditions will also be discussed.     

霉酚酸酯对小鼠肺纤维化组织中转化生长因子-β1表达的影响

目的探讨霉酚酸酯(mycophenolate mofetil,MMF)对博莱霉素(bleomycin,BLM)诱导的小鼠肺纤维化组织中转化生长因子-β1(transforming growth factor-β1,TGF-β1)表达的影响。方法将C57BL/6小鼠随机分为6组:正常对照组、MMF对照组、BLM模型组、MMF低(20 mg/kg)、中(60 mg/kg)、高(100 mg/kg)剂量干预组,每组6只。BLM模型组和MMF 3个干预组经气管注入BLM(6 mg/kg),正常对照组和MMF对照组注入等量无菌生理盐水;次日按MMF对照组和MMF干预低、中、高剂量组小鼠体重计算MMF给药量,灌胃小鼠,每日1次,连续14 d,正常对照组和BLM模型组用等体积的双蒸水灌胃。灌胃第16天采集小鼠肺脏标本,经HE、Masson染色,从组织形态学上观察肺组织纤维化情况并进行Aschcroft评分;RT-PCR法检测小鼠肺组织中TGF-β1基因mRNA的转录水平;Western blot法检测小鼠肺组织中TGF-β1蛋白的表达水平。结果 BLM诱导的小鼠肺纤维化改变显著,Ashcroft评分较正常对照组显著增高(P<0.01),表明小鼠肺纤维化模型构建成功;MMF高剂量干预组肺组织损伤减轻,炎细胞浸润及胶原沉积减少,Ashcroft评分显著降低(P=0.000)。MMF高剂量干预组与BLM模型组比较,TGF-β1基因mRNA的转录水平及蛋白的表达水平均明显减低(P<0.05);而MMF低、中剂量干预组与BLM模型组之间、MMF对照组与正常对照组之间,差异均无统计学意义(P>0.05)。结论高剂量的MMF(100 mg/kg)可抑制BLM诱导的肺纤维化小鼠肺组织中TGF-β1基因mRNA的转录水平及蛋白表达水平,有望成为治疗肺纤维化的理想药物。     

Nuclear Receptor Nur77 Controls Cardiac Fibrosis through Distinct Actions on Fibroblasts and Cardiomyocytes

Fibrosis is a hallmark of adverse cardiac remodeling, which promotes heart failure, but it is also an essential repair mechanism to prevent cardiac rupture, signifying the importance of appropriate regulation of this process. In the remodeling heart, cardiac fibroblasts (CFs) differentiate into myofibroblasts (MyoFB), which are the key mediators of the fibrotic response. Additionally, cardiomyocytes are involved by providing pro-fibrotic cues. Nuclear receptor Nur77 is known to reduce cardiac hypertrophy and associated fibrosis; however, the exact function of Nur77 in the fibrotic response is yet unknown. Here, we show that Nur77-deficient mice exhibit severe myocardial wall thinning, rupture and reduced collagen fiber density after myocardial infarction and chronic isoproterenol (ISO) infusion. Upon Nur77 knockdown in cultured rat CFs, expression of MyoFB markers and extracellular matrix proteins is reduced after stimulation with ISO or transforming growth factor–β (TGF-β). Accordingly, Nur77-depleted CFs produce less collagen and exhibit diminished proliferation and wound closure capacity. Interestingly, Nur77 knockdown in neonatal rat cardiomyocytes results in increased paracrine induction of MyoFB differentiation, which was blocked by TGF-β receptor antagonism. Taken together, Nur77-mediated regulation involves CF-intrinsic promotion of CF-to-MyoFB transition and inhibition of cardiomyocyte-driven paracrine TGF-β-mediated MyoFB differentiation. As such, Nur77 provides distinct, cell-specific regulation of cardiac fibrosis.