Cytokine receptor-like factor 1 (CRLF1) promotes cardiac fibrosis via ERK1/2 signaling pathway

Shenjian LUO; Zhi YANG; Ruxin CHEN; Danming YOU; Fei TENG; Youwen YUAN; Wenhui LIU; Jin LI; Huijie ZHANG

doi:10.1631/jzus.B2200506

Your Location：

Home >

Browse articles >

Cytokine receptor-like factor 1 (CRLF1) promotes cardiac fibrosis via ERK1/2 signaling pathway

Scan for full text

Alert me when the article has been cited

Submit

Research Article | Updated：2023-08-08

Cytokine receptor-like factor 1 (CRLF1) promotes cardiac fibrosis via ERK1/2 signaling pathway
Cytokine receptor-like factor 1 (CRLF1) promotes cardiac fibrosis via ERK1/2 signaling pathway
细胞因子受体样因子1(CRLF1)通过ERK1/2信号通路促进心脏纤维化
Journal of Zhejiang University-SCIENCE B(Biomedicine & Biotechnology) Vol. 24, Issue 8, Pages: 682-697(2023)
Affiliations：

1.Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
2.Guangdong Provincial Key Laboratory of Shock and Microcirculation, Southern Medical University, Guangzhou 510515, China
3.State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
4.Department of Endocrinology, Shanxi Medical University Affiliated Second Hospital, Taiyuan 030001, China
Funds：
DOI：10.1631/jzus.B2200506
CLC：
CSTR：

Shenjian LUO, Zhi YANG, Ruxin CHEN, et al. Cytokine receptor-like factor 1 (CRLF1) promotes cardiac fibrosis via ERK1/2 signaling pathway. [J]. Journal of Zhejiang University-SCIENCE B(Biomedicine & Biotechnology) 24(8):682-697(2023)
DOI：

Shenjian LUO, Zhi YANG, Ruxin CHEN, et al. Cytokine receptor-like factor 1 (CRLF1) promotes cardiac fibrosis via ERK1/2 signaling pathway. [J]. Journal of Zhejiang University-SCIENCE B(Biomedicine & Biotechnology) 24(8):682-697(2023) DOI： 10.1631/jzus.B2200506.

摘要

心脏纤维化是心脏疾病患者发病和死亡的原因之一。抗纤维化治疗是一种治疗心脏疾病的重要手段，但目前对纤维化的机制仍缺乏深入了解。本研究旨在确定细胞因子受体样因子1（CRLF1）在心脏纤维化中的功能并阐明其调节机制。我们发现,CRLF1,主要在心脏成纤维细胞中表达；无论是在心肌梗死诱导的小鼠心脏纤维化模型还是在转化生长因子-β1（TGF-‍β1）刺激的小鼠和人心脏成纤维细胞中，,CRLF1,表达均上调。本研究在使用或不使用TGF-β1刺激的新生乳鼠心脏成纤维细胞（NMCFs）中开展了,CRLF1,的功能获得和丧失实验。在TGF-β1刺激或不刺激的情况下，,CRLF1,的过表达均可增加NMCFs的细胞活力、胶原生成、细胞增殖能力及肌成纤维细胞转化，而,CRLF1,沉默则具有相反效果。应用细胞外信号调节激酶1/2（ERK1/2）信号通路抑制剂以及包括SMAD依赖和非依赖信号在内的不同TGF-β1下游信号通路抑制剂来开展机制研究。CRLF1通过激活ERK1/2信号通路发挥其功能。此外，,CRLF1,在TGF-β1处理的NMCFs中表达上调是由SMAD依赖性通路介导，而不是SMAD非依赖性通路介导。总而言之，心脏纤维化中TGF-β1/SMAD信号通路的激活增加了,CRLF1,的表达。随后，CRLF1通过激活ERK1/2信号通路加重了心脏纤维化。因此，CRLF1可作为一个干预和治疗心脏纤维化的新的潜在靶点。

Abstract

Cardiac fibrosis is a cause of morbidity and mortality in people with heart disease. Anti-fibrosis treatment is a significant therapy for heart disease, but there is still no thorough understanding of fibrotic mechanisms. This study was carried out to ascertain the functions of cytokine receptor-like factor 1 (CRLF1) in cardiac fibrosis and clarify its regulatory mechanisms. We found that ,CRLF1, was expressed predominantly in cardiac fibroblasts. Its expression was up-regulated not only in a mouse heart fibrotic model induced by myocardial infarction, but also in mouse and human cardiac fibroblasts provoked by transforming growth factor-‍β1 (TGF‍-‍β1). Gain- and loss-of-function experiments of ,CRLF1, were carried out in neonatal mice cardiac fibroblasts (NMCFs) with or without TGF-‍β1 stimulation. ,CRLF1 ,overexpression increased cell viability, collagen production, cell proliferation capacity, and myofibroblast transformation of NMCFs with or without TGF‍-‍β1 stimulation, while silencing of ,CRLF1, had the opposite effects. An inhibitor of the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway and different inhibitors of TGF-‍β1 signaling cascades, comprising mothers against decapentaplegic homolog (SMAD)‍-dependent and SMAD-independent pathways, were applied to investigate the mechanisms involved. CRLF1 exerted its functions by activating the ERK1/2 signaling pathway. Furthermore, the SMAD-dependent pathway, not the SMAD-independent pathway, was responsible for ,CRLF1, up-regulation in NMCFs treated with TGF-‍β1. In summary, activation of the TGF-‍β1/SMAD signaling pathway in cardiac fibrosis increased ,CRLF1, expression. CRLF1 then aggravated cardiac fibrosis by activating the ERK1/2 signaling pathway. CRLF1 could become a novel potential target for intervention and remedy of cardiac fibrosis.

关键词

细胞因子受体样因子1（CRLF1）转化生长因子-β1（TGF-β1）/SMAD信号通路细胞外信号调节激酶1/2（ERK1/2）信号通路心脏纤维化肌成纤维细胞转化细胞外基质（ECM）

Keywords

Cytokine receptor-like factor 1 (CRLF1)TGF‍-‍β1/SMAD signaling pathwayERK1/2 signaling pathwayCardiac fibrosisMyofibroblast transformationExtracellular matrix (ECM)

references

Bacmeister L, Schwarzl M, Warnke S, et al., 2019. Inflammation and fibrosis in murine models of heart failure. Basic Res Cardiol, 114(3):19. https://doi.org/10.1007/s00395-019-0722-5https://doi.org/10.1007/s00395-019-0722-5

Barron L, Wynn TA, 2011. Fibrosis is regulated by Th2 and Th17 responses and by dynamic interactions between fibroblasts and macrophages. Am J Physiol Gastrointest Liver Physiol, 300(5):G723-728. https://doi.org/10.1152/ajpgi.00414.2010https://doi.org/10.1152/ajpgi.00414.2010

Bashey RI, Martinez-Hernandez A, Jimenez SA, 1992. Isolation, characterization, and localization of cardiac collagen type VI. Associations with other extracellular matrix components. Circ Res, 70(5):1006-1017. https://doi.org/10.1161/01.res.70.5.1006https://doi.org/10.1161/01.res.70.5.1006

Berk BC, Fujiwara K, Lehoux S, 2007. ECM remodeling in hypertensive heart disease. J Clin Invest, 117(3):568-575. https://doi.org/10.1172/JCI31044https://doi.org/10.1172/JCI31044

Biernacka A, Cavalera M, Wang JH, et al., 2015. Smad3 signaling promotes fibrosis while preserving cardiac and aortic geometry in obese diabetic mice. Circ Heart Fail, 8(4):788-798. https://doi.org/10.1161/CIRCHEARTFAILURE.114.001963https://doi.org/10.1161/CIRCHEARTFAILURE.114.001963

Brown RD, Ambler SK, Mitchell MD, et al., 2005. The CARDIAC FIBROBLAST: therapeutic target in myocardial remodeling and failure. Annu Rev Pharmacol Toxicol, 45:657-687. https://doi.org/10.1146/annurev.pharmtox.45.120403.095802https://doi.org/10.1146/annurev.pharmtox.45.120403.095802

Buers I, Persico I, Schöning L, et al., 2020. Crisponi/cold-induced sweating syndrome: differential diagnosis, pathogenesis and treatment concepts. Clin Genet, 97(1):209-221. https://doi.org/10.1111/cge.13639https://doi.org/10.1111/cge.13639

Busch A, Žarković M, Lowe C, et al., 2017. Mutations in CRLF1 cause familial achalasia. Clin Genet, 92(1):‍104-108. https://doi.org/10.1111/cge.12953https://doi.org/10.1111/cge.12953

Chaffin M, Papangeli I, Simonson B, et al., 2022. Single-nucleus profiling of human dilated and hypertrophic cardiomyopathy. Nature, 608(7921):174-180. https://doi.org/10.1038/s41586-022-04817-8https://doi.org/10.1038/s41586-022-04817-8

Childers RC, Sunyecz I, West TA, et al., 2019. Role of the cytoskeleton in the development of a hypofibrotic cardiac fibroblast phenotype in volume overload heart failure. Am J Physiol Heart Circ Physiol, 316(3):H596-H608. https://doi.org/10.1152/ajpheart.00095.2018https://doi.org/10.1152/ajpheart.00095.2018

Chou CH, Hung CS, Liao CW, et al., 2018. IL-6 trans-signalling contributes to aldosterone-induced cardiac fibrosis. Cardiovasc Res, 114(5):690-702. https://doi.org/10.1093/cvr/cvy013https://doi.org/10.1093/cvr/cvy013

Derynck R, Zhang YE, 2003. Smad-dependent and Smad-independent pathways in TGF-‍β family signalling. Nature, 425(6958):577-584. https://doi.org/10.1038/nature02006https://doi.org/10.1038/nature02006

Dewald O, Ren GF, Duerr GD, et al., 2004. Of mice and dogs: species-specific differences in the inflammatory response following myocardial infarction. Am J Pathol, 164(2):665-677. https://doi.org/10.1016/S0002-9440(10)63154-9https://doi.org/10.1016/S0002-9440(10)63154-9

Disertori M, Masè M, Ravelli F, 2017. Myocardial fibrosis predicts ventricular tachyarrhythmias. Trends Cardiovasc Med, 27(5):363-372. https://doi.org/10.1016/j.tcm.2017.01.011https://doi.org/10.1016/j.tcm.2017.01.011

Fernández-Alfonso MS, Ruilope LM, 2014. One step forward for serelaxin as a promising therapy in cardiac fibrosis. Hypertension, 64(2):229-230. https://doi.org/10.1161/HYPERTENSIONAHA.114.03642https://doi.org/10.1161/HYPERTENSIONAHA.114.03642

Frangogiannis NG, 2017. The extracellular matrix in myocardial injury, repair, and remodeling. J Clin Invest, 127(5):1600-1612. https://doi.org/10.1172/JCI87491https://doi.org/10.1172/JCI87491

Frangogiannis NG, 2019. Cardiac fibrosis: cell biological mechanisms, molecular pathways and therapeutic opportunities. Mol Aspects Med, 65:70-99. https://doi.org/10.1016/j.mam.2018.07.001https://doi.org/10.1016/j.mam.2018.07.001

Frangogiannis NG, 2020. Transforming growth factor-‍β in tissue fibrosis. J Exp Med, 217(3):e20190103. https://doi.org/10.1084/jem.20190103https://doi.org/10.1084/jem.20190103

Gupta S, Ge Y, Singh A, et al., 2021. Multimodality imaging assessment of myocardial fibrosis. JACC Cardiovasc Imaging, 14(12):2457-2469. https://doi.org/10.1016/j.jcmg.2021.01.027https://doi.org/10.1016/j.jcmg.2021.01.027

Hanna A, Frangogiannis NG, 2019. The role of the TGF‍-‍β superfamily in myocardial infarction. Front Cardiovasc Med, 6:140. https://doi.org/10.3389/fcvm.2019.00140https://doi.org/10.3389/fcvm.2019.00140

Herholz J, Meloni A, Marongiu M, et al., 2011. Differential secretion of the mutated protein is a major component affecting phenotypic severity in CRLF1-associated disorders. Eur J Hum Genet, 19(5):525-533. https://doi.org/10.1038/ejhg.2010.253https://doi.org/10.1038/ejhg.2010.253

Horbelt D, Denkis A, Knaus P, 2012. A portrait of transforming growth factor β superfamily signalling: background matters. Int J Biochem Cell Biol, 44(3):469-474. https://doi.org/10.1016/j.biocel.2011.12.013https://doi.org/10.1016/j.biocel.2011.12.013

Hu HH, Chen DQ, Wang YN, et al., 2018. New insights into TGF‍-‍β/Smad signaling in tissue fibrosis. Chem Biol Interact, 292:76-83. https://doi.org/10.1016/j.cbi.2018.07.008https://doi.org/10.1016/j.cbi.2018.07.008

Janicki JS, Brower GL, 2002. The role of myocardial fibrillar collagen in ventricular remodeling and function. J Card Fail, 8(6):S319-S325. https://doi.org/10.1054/jcaf.2002.129260https://doi.org/10.1054/jcaf.2002.129260

Jugdutt BI, 2003. Ventricular remodeling after infarction and the extracellular collagen matrix: when is enough enough? Circulation, 108(11):1395-1403. https://doi.org/10.1161/01.CIR.0000085658.98621.49https://doi.org/10.1161/01.CIR.0000085658.98621.49

Koenig AL, Shchukina I, Amrute J, et al., 2022. Single-cell transcriptomics reveals cell-type-specific diversification in human heart failure. Nat Cardiovasc Res, 1(3):263-280. https://doi.org/10.1038/s44161-022-00028-6https://doi.org/10.1038/s44161-022-00028-6

Kong P, Christia P, Frangogiannis NG, 2014. The pathogenesis of cardiac fibrosis. Cell Mol Life Sci, 71(4):549-574. https://doi.org/10.1007/s00018-013-1349-6https://doi.org/10.1007/s00018-013-1349-6

JrLattanzio FA, Tiangco D, Osgood C, et al., 2005. Cocaine increases intracellular calcium and reactive oxygen species, depolarizes mitochondria, and activates genes associated with heart failure and remodeling. Cardiovasc Toxicol, 5(4):377-389. https://doi.org/10.1385/ct:5:4:377https://doi.org/10.1385/ct:5:4:377

Lei H, Wu D, Wang JY, et al., 2015. C1q/tumor necrosis factor-related protein-6 attenuates post-infarct cardiac fibrosis by targeting RhoA/MRTF-A pathway and inhibiting myofibroblast differentiation. Basic Res Cardiol, 110(4):35. https://doi.org/10.1007/s00395-015-0492-7https://doi.org/10.1007/s00395-015-0492-7

Li RK, Li GM, Mickle DAG, et al., 1997. Overexpression of transforming growth factor-‍β1 and insulin-like growth factor-I in patients with idiopathic hypertrophic cardiomyopathy. Circulation, 96(3):‍874-881. https://doi.org/10.1161/01.cir.96.3.874https://doi.org/10.1161/01.cir.96.3.874

Li YF, Xun J, Wang BT, et al., 2021. miR-3065-3p promotes stemness and metastasis by targeting CRLF1 in colorectal cancer. J Transl Med, 19:429. https://doi.org/10.1186/s12967-021-03102-yhttps://doi.org/10.1186/s12967-021-03102-y

Lodyga M, Hinz B, 2020. TGF‍-‍β1—a truly transforming growth factor in fibrosis and immunity. Semin Cell Dev Biol, 101:123-139. https://doi.org/10.1016/j.semcdb.2019.12.010https://doi.org/10.1016/j.semcdb.2019.12.010

Looyenga BD, Resau J, MacKeigan JP, 2013. Cytokine receptor-like factor 1 (CRLF1) protects against 6-hydroxydopamine toxicity independent of the gp130/JAK signaling pathway. PLoS ONE, 8(6):e66548. https://doi.org/10.1371/journal.pone.0066548https://doi.org/10.1371/journal.pone.0066548

López B, Ravassa S, Moreno MU, et al., 2021. Diffuse myocardial fibrosis: mechanisms, diagnosis and therapeutic approaches. Nat Rev Cardiol, 18(7):479-498. https://doi.org/10.1038/s41569-020-00504-1https://doi.org/10.1038/s41569-020-00504-1

Magaye RR, Savira F, Hua Y, et al., 2020. Exogenous dihydrosphingosine 1 phosphate mediates collagen synthesis in cardiac fibroblasts through JAK/STAT signalling and regulation of TIMP1. Cell Signal, 72:109629. https://doi.org/10.1016/j.cellsig.2020.109629https://doi.org/10.1016/j.cellsig.2020.109629

Magaye RR, Savira F, Hua Y, et al., 2021a. Attenuating PI3K/Akt-mTOR pathway reduces dihydrosphingosine 1 phosphate mediated collagen synthesis and hypertrophy in primary cardiac cells. Int J Biochem Cell Biol, 134:105952. https://doi.org/10.1016/j.biocel.2021.105952https://doi.org/10.1016/j.biocel.2021.105952

Magaye RR, Savira F, Xiong X, et al., 2021b. Dihydrosphingosine driven enrichment of sphingolipids attenuates TGFβ induced collagen synthesis in cardiac fibroblasts. IJC Heart Vasc, 35:100837. https://doi.org/10.1016/j.ijcha.2021.100837https://doi.org/10.1016/j.ijcha.2021.100837

Mantovani A, Sica A, Locati M, 2005. Macrophage polarization comes of age. Immunity, 23(4):344-346. https://doi.org/10.1016/j.immuni.2005.10.001https://doi.org/10.1016/j.immuni.2005.10.001

Meng JX, Qin YY, Chen JZ, et al., 2020. Treatment of hypertensive heart disease by targeting Smad3 signaling in mice. Mol Ther Methods Clin Dev, 18:791-802. https://doi.org/10.1016/j.omtm.2020.08.003https://doi.org/10.1016/j.omtm.2020.08.003

Meng XM, Nikolic-Paterson DJ, Lan HY, 2016. TGF‍-‍β: the master regulator of fibrosis. Nat Rev Nephrol, 12(6):325-338. https://doi.org/10.1038/nrneph.2016.48https://doi.org/10.1038/nrneph.2016.48

Nagaraju CK, Robinson EL, Abdesselem M, et al., 2019. Myofibroblast phenotype and reversibility of fibrosis in patients with end-stage heart failure. J Am Coll Cardiol, 73(18):2267-2282. https://doi.org/10.1016/j.jacc.2019.02.049https://doi.org/10.1016/j.jacc.2019.02.049

Nguyen MN, Kiriazis H, Gao XM, et al., 2017. Cardiac fibrosis and arrhythmogenesis. Compr Physiol, 7(3):1009-1049. https://doi.org/10.1002/cphy.c160046https://doi.org/10.1002/cphy.c160046

Nguyen TP, Qu ZL, Weiss JN, 2014. Cardiac fibrosis and arrhythmogenesis: the road to repair is paved with perils. J Mol Cell Cardiol, 70:83-91. https://doi.org/10.1016/j.yjmcc.2013.10.018https://doi.org/10.1016/j.yjmcc.2013.10.018

Perestrelo AR, Silva AC, Oliver-De La Cruz J, et al., 2021. Multiscale analysis of extracellular matrix remodeling in the failing heart. Circ Res, 128(1):24-38. https://doi.org/10.1161/CIRCRESAHA.120.317685https://doi.org/10.1161/CIRCRESAHA.120.317685

Roubille F, Busseuil D, Merlet N, et al., 2014. Investigational drugs targeting cardiac fibrosis. Expert Rev Cardiovasc Ther, 12(1):111-125. https://doi.org/10.1586/14779072.2013.839942https://doi.org/10.1586/14779072.2013.839942

Scalise RFM, de Sarro R, Caracciolo A, et al., 2021. Fibrosis after myocardial infarction: an overview on cellular processes, molecular pathways, clinical evaluation and prognostic value. Med Sci (Basel), 9(1):16. https://doi.org/10.3390/medsci9010016https://doi.org/10.3390/medsci9010016

Schmierer B, Hill CS, 2007. TGFβ‍-SMAD signal transduction: molecular specificity and functional flexibility. Nat Rev Mol Cell Biol, 8(12):970-982. https://doi.org/10.1038/nrm2297https://doi.org/10.1038/nrm2297

Schuetze KB, McKinsey TA, Long CS, 2014. Targeting cardiac fibroblasts to treat fibrosis of the heart: focus on HDACs. J Mol Cell Cardiol, 70:100-107. https://doi.org/10.1016/j.yjmcc.2014.02.015https://doi.org/10.1016/j.yjmcc.2014.02.015

Shen Y, Teng YS, Lv YP, et al., 2020. PD-1 does not mark tumor-infiltrating CD8+ T cell dysfunction in human gastric cancer. J Immunother Cancer, 8(2):e000422. https://doi.org/10.1136/jitc-2019-000422https://doi.org/10.1136/jitc-2019-000422

Shirwany A, Weber KT, 2006. Extracellular matrix remodeling in hypertensive heart disease. J Am Coll Cardiol, 48(1):97-98. https://doi.org/10.1016/j.jacc.2006.04.004https://doi.org/10.1016/j.jacc.2006.04.004

Singh R, Kaundal RK, Zhao BY, et al., 2021. Resistin induces cardiac fibroblast-myofibroblast differentiation through JAK/STAT3 and JNK/c-Jun signaling. Pharmacol Res, 167:105414. https://doi.org/10.1016/j.phrs.2020.105414https://doi.org/10.1016/j.phrs.2020.105414

Stefanovic L, Stefanovic B, 2012. Role of cytokine receptor-like factor 1 in hepatic stellate cells and fibrosis. World J Hepatol, 4(12):356-364. https://doi.org/10.4254/wjh.v4.i12.356https://doi.org/10.4254/wjh.v4.i12.356

Stratton MS, Bagchi RA, Felisbino MB, et al., 2019. Dynamic chromatin targeting of BRD4 stimulates cardiac fibroblast activation. Circ Res, 125(7):662-677. https://doi.org/10.1161/CIRCRESAHA.119.315125https://doi.org/10.1161/CIRCRESAHA.119.315125

Sundararaj K, Pleasant DL, Moschella PC, et al., 2016. mTOR complexes repress hypertrophic agonist-stimulated expression of connective tissue growth factor in adult cardiac muscle cells. J Cardiovasc Pharmacol, 67(2):110-120. https://doi.org/10.1097/FJC.0000000000000322https://doi.org/10.1097/FJC.0000000000000322

The Tabula Muris Consortium, Overall Coordination, Logistical Coordination, et al., 2018. Single-cell transcriptomics of 20 mouse organs creates a Tabula muris. Nature, 562(7727):367-372. https://doi.org/10.1038/s41586-018-0590-4https://doi.org/10.1038/s41586-018-0590-4

Tu YG, Wu TQ, Dai AZ, et al., 2011. Cell division autoantigen 1 enhances signaling and the profibrotic effects of transforming growth factor-‍β in diabetic nephropathy. Kidney Int, 79(2):199-209. https://doi.org/10.1038/ki.2010.374https://doi.org/10.1038/ki.2010.374

Tucker NR, Chaffin M, Fleming SJ, et al., 2020. Transcriptional and cellular diversity of the human heart. Circulation, 142(5):466-482. https://doi.org/10.1161/CIRCULATIONAHA.119.045401https://doi.org/10.1161/CIRCULATIONAHA.119.045401

Tuleta I, Frangogiannis NG, 2021. Fibrosis of the diabetic heart: clinical significance, molecular mechanisms, and therapeutic opportunities. Adv Drug Deliv Rev, 176:113904. https://doi.org/10.1016/j.addr.2021.113904https://doi.org/10.1016/j.addr.2021.113904

Umbarkar P, Ejantkar S, Tousif S, et al., 2021. Mechanisms of fibroblast activation and myocardial fibrosis: lessons learned from FB-specific conditional mouse models. Cells, 10(9):2412. https://doi.org/10.3390/cells10092412https://doi.org/10.3390/cells10092412

Wang JC, Zhao HK, Zheng L, et al., 2021. FGF19/SOCE/NFATc2 signaling circuit facilitates the self-renewal of liver cancer stem cells. Theranostics, 11(10):5045-5060. https://doi.org/10.7150/thno.56369https://doi.org/10.7150/thno.56369

Wang XW, Ma JP, Zhang SS, et al., 2021. G protein-coupled estrogen receptor 30 reduces transverse aortic constriction-induced myocardial fibrosis in aged female mice by inhibiting the ERK1/2-MMP-9 signaling pathway. Front Pharmacol, 12:731609. https://doi.org/10.3389/fphar.2021.731609https://doi.org/10.3389/fphar.2021.731609

Wang ZY, Shen JK, Sun W, et al., 2019. Antitumor activity of raddeanin A is mediated by jun amino-terminal kinase activation and signal transducer and activator of transcription 3 inhibition in human osteosarcoma. Cancer Sci, 110(5):1746-1759. https://doi.org/10.1111/cas.14008https://doi.org/10.1111/cas.14008

Weber KT, 1989. Cardiac interstitium in health and disease: the fibrillar collagen network. J Am Coll Cardiol, 13(7):1637-1652. https://doi.org/10.1016/0735-1097(89)90360-4https://doi.org/10.1016/0735-1097(89)90360-4

Wen JX, Li MJ, Zhang WW, et al., 2022. Role of higenamine in heart diseases: a mini-review. Front Pharmacol, 12:798495. https://doi.org/10.3389/fphar.2021.798495https://doi.org/10.3389/fphar.2021.798495

Westermann D, van Linthout S, Dhayat S, et al., 2007. Tumor necrosis factor-alpha antagonism protects from myocardial inflammation and fibrosis in experimental diabetic cardiomyopathy. Basic Res Cardiol, 102(6):500-507. https://doi.org/10.1007/s00395-007-0673-0https://doi.org/10.1007/s00395-007-0673-0

Wynn TA, 2008. Cellular and molecular mechanisms of fibrosis. J Pathol, 214(2):199-210. https://doi.org/10.1002/path.2277https://doi.org/10.1002/path.2277

Xia Y, Dobaczewski M, Gonzalez-Quesada C, et al., 2011. Endogenous thrombospondin 1 protects the pressure-overloaded myocardium by modulating fibroblast phenotype and matrix metabolism. Hypertension, 58(5):‍902-911. https://doi.org/10.1161/HYPERTENSIONAHA.111.175323https://doi.org/10.1161/HYPERTENSIONAHA.111.175323

Yamaguchi O, Watanabe T, Nishida K, et al., 2004. Cardiac-specific disruption of the c-raf-1 gene induces cardiac dysfunction and apoptosis. J Clin Invest, 114(7):937-943. https://doi.org/10.1172/JCI20317https://doi.org/10.1172/JCI20317

Yu P, Ma SC, Dai XC, et al., 2020. Elabela alleviates myocardial ischemia reperfusion-induced apoptosis, fibrosis and mitochondrial dysfunction through PI3K/AKT signaling. Am J Transl Res, 12(8):4467-4477.

Yu ST, Zhong Q, Chen RH, et al., 2018. CRLF1 promotes malignant phenotypes of papillary thyroid carcinoma by activating the MAPK/ERK and PI3K/AKT pathways. Cell Death Dis, 9(3):371. https://doi.org/10.1038/s41419-018-0352-0https://doi.org/10.1038/s41419-018-0352-0

Yu ST, Sun BH, Ge JN, et al., 2020. CRLF1-MYH9 interaction regulates proliferation and metastasis of papillary thyroid carcinoma through the ERK/ETV4 axis. Front Endocrinol (Lausanne), 11:535. https://doi.org/10.3389/fendo.2020.00535https://doi.org/10.3389/fendo.2020.00535

Zhao K, Zhang J, Xu TH, et al., 2021. Low‐intensity pulsed ultrasound ameliorates angiotensin II-induced cardiac fibrosis by alleviating inflammation via a caveolin-1-dependent pathway. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 22(10):818-838. https://doi.org/10.1631/jzus.B2100130https://doi.org/10.1631/jzus.B2100130

Zheng ZY, Ao X, Li P, et al., 2020. CRLF1 is a key regulator in the ligamentum flavum hypertrophy. Front Cell Dev Biol, 8:858. https://doi.org/10.3389/fcell.2020.00858https://doi.org/10.3389/fcell.2020.00858

Views

Downloads

CSCD

Tools

Publicity Resources

Low‐intensity pulsed ultrasound ameliorates angiotensin II-induced cardiac fibrosis by alleviating inflammation via a caveolin-1-dependent pathway

Hemodialysis bilayer bionic blood vessels developed by the mechanical stimulation of HBX-transfected hepatic stellate cells

Related Author

No data

Related Institution

Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University

Key Laboratory of Modern Acoustics, Department of Physics, Collaborative Innovation Center of Advanced Microstructure, Nanjing University

Departments of Genetics, Pediatrics, and Medicine (Cardiology), Wilf Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx

Department of Oncology and Vascular Interventional Radiology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University

School of Medicine, Xiamen University

Address：Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou, China Postal code：310027
Tel：+86-571-87952783 Email：cjzhang@zju.edu.cn
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备09064830号-19 京公网安备11010802024621
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰