Skip to main content
SpringerLink
Log in

TUG1 knockdown suppresses cardiac fibrosis after myocardial infarction

  • Published:
Mammalian Genome Aims and scope Submit manuscript

Abstract

Cardiac fibrosis is involved in myocardial remodeling following acute myocardial infarction (AMI), which can result in heart failure, arrhythmias and even sudden cardiac death. Investigating the molecular mechanisms of cardiac fibrosis in acute myocardial infarction (AMI) is essential for better understanding this pathology. The current study aims to investigate the effect of TUG1 on cardiac fibrosis after AMI and elucidated the underlying molecular mechanism of AMI. Rats were randomly divided into four groups (sham-operation group, myocardial infarction group (AMI group), si-NC treated group and si-TUG1 treated group). The biological behavior of cardiac fibroblasts treated with TGF-β1after being transfected by si-TUG1 or miR-590 mimic or miR-590 inhibitor or FGF1 mimic or a combination was evaluated using the cell counting kit-8 (CCK8) and Transwell assays. SatarBase v2.0 was used to predict the target microRNAs binding site candidates with TUG1 and FGF1. Western blot and recovery experiments were used to explore the potential mechanism. TUG1 expression was up-regulated and knockdown of TUG1 improved cardiac function in AMI rats. Knockdown of TUG1 suppressed cell viability and migration and improved collagen production of TGF-β1 treated cardiac fibroblasts. SatarBase v2.0 showed TUG1 served as a sponge for miR-590 and FGF1 is a direct target of miR-590. TUG1 expression was increased in AMI tissue and cardiac fibroblasts treated with TGF-β1. TUG1 knockdown suppressed the biological process of cardiac fibroblasts treated with TGF-β1 by sponging miR-590.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Ai Y, Chen M, Liu J, Ren L, Yan X, Feng Y (2020) lncRNA TUG1 promotes endometrial fibrosis and inflammation by sponging miR-590-5p to regulate Fasl in intrauterine adhesions. Int Immunopharmacol 86:106703

    Article  CAS  Google Scholar 

  • Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136:215–233

    Article  CAS  Google Scholar 

  • Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, de Ferranti SD, Floyd J, Fornage M, Gillespie C, Isasi CR, Jimenez MC, Jordan LC, Judd SE, Lackland D, Lichtman JH, Lisabeth L, Liu S, Longenecker CT, Mackey RH, Matsushita K, Mozaffarian D, Mussolino ME, Nasir K, Neumar RW, Palaniappan L, Pandey DK, Thiagarajan RR, Reeves MJ, Ritchey M, Rodriguez CJ, Roth GA, Rosamond WD, Sasson C, Towfighi A, Tsao CW, Turner MB, Virani SS, Voeks JH, Willey JZ, Wilkins JT, Wu JH, Alger HM, Wong SS, Muntner P (2017) Heart disease and stroke statistics-2017 update: a report from the American Heart Association. Circulation 135:e146–e603

    Article  Google Scholar 

  • Bujak M, Frangogiannis NG (2007) The role of TGF-beta signaling in myocardial infarction and cardiac remodeling. Cardiovasc Res 74:184–195

    Article  CAS  Google Scholar 

  • Geisler S, Coller J (2013) RNA in unexpected places: long non-coding RNA functions in diverse cellular contexts. Nat Rev Mol Cell Biol 14:699–712

    Article  CAS  Google Scholar 

  • Han X, Hong Y, Zhang K (2018) TUG1 is involved in liver fibrosis and activation of HSCs by regulating miR-29b. Biochem Biophys Res Commun 503:1394–1400

    Article  CAS  Google Scholar 

  • He S, Shi D, Han Z, Dong Z, Xie Y, Zhang F, Zeng W, Yi Q (2019) Heparinized silk fibroin hydrogels loading FGF1 promote the wound healing in rats with full-thickness skin excision. Biomed Eng Online 18:97

    Article  Google Scholar 

  • Huang S, Zhang L, Song J, Wang Z, Huang X, Guo Z, Chen F, Zhao X (2019) Long noncoding RNA MALAT1 mediates cardiac fibrosis in experimental postinfarct myocardium mice model. J Cell Physiol 234:2997–3006

    Article  CAS  Google Scholar 

  • Liu X, Xu Y, Deng Y, Li H (2018) MicroRNA-223 regulates cardiac fibrosis after myocardial infarction by targeting RASA1. Cell Physiol Biochem 46:1439–1454

    Article  CAS  Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402–408

    Article  CAS  Google Scholar 

  • MacKenzie B, Korfei M, Henneke I, Sibinska Z, Tian X, Hezel S, Dilai S, Wasnick R, Schneider B, Wilhelm J, El Agha E, Klepetko W, Seeger W, Schermuly R, Gunther A, Bellusci S (2015) Increased FGF1-FGFRc expression in idiopathic pulmonary fibrosis. Respir Res 16:83

    Article  Google Scholar 

  • Mattick JS, Rinn JL (2015) Discovery and annotation of long noncoding RNAs. Nat Struct Mol Biol 22:5–7

    Article  CAS  Google Scholar 

  • Mercer TR, Dinger ME, Mattick JS (2009) Long non-coding RNAs: insights into functions. Nat Rev Genet 10:155–159

    Article  CAS  Google Scholar 

  • Pan Z, Sun X, Shan H, Wang N, Wang J, Ren J, Feng S, Xie L, Lu C, Yuan Y, Zhang Y, Wang Y, Lu Y, Yang B (2012) MicroRNA-101 inhibited postinfarct cardiac fibrosis and improved left ventricular compliance via the FBJ osteosarcoma oncogene/transforming growth factor-beta1 pathway. Circulation 126:840–850

    Article  CAS  Google Scholar 

  • Rapicavoli NA, Blackshaw S (2009) New meaning in the message: noncoding RNAs and their role in retinal development. Dev Dyn 238:2103–2114

    Article  CAS  Google Scholar 

  • Shinde AV, Frangogiannis NG (2014) Fibroblasts in myocardial infarction: a role in inflammation and repair. J Mol Cell Cardiol 70:74–82

    Article  CAS  Google Scholar 

  • Small EM, Frost RJ, Olson EN (2010) MicroRNAs add a new dimension to cardiovascular disease. Circulation 121:1022–1032

    Article  Google Scholar 

  • Su Q, Liu Y, Lv XW, Dai RX, Yang XH, Kong BH (2020) LncRNA TUG1 mediates ischemic myocardial injury by targeting miR-132-3p/HDAC3 axis. Am J Physiol Heart Circ Physiol 318:H332–H344

    Article  CAS  Google Scholar 

  • Sun F, Zhuang Y, Zhu H, Wu H, Li D, Zhan L, Yang W, Yuan Y, Xie Y, Yang S, Luo S, Jiang W, Zhang J, Pan Z, Lu Y (2019) LncRNA PCFL promotes cardiac fibrosis via miR-378/GRB2 pathway following myocardial infarction. J Mol Cell Cardiol 133:188–198

    Article  CAS  Google Scholar 

  • Tay Y, Rinn J, Pandolfi PP (2014) The multilayered complexity of ceRNA crosstalk and competition. Nature 505:344–352

    Article  CAS  Google Scholar 

  • Travers JG, Kamal FA, Robbins J, Yutzey KE, Blaxall BC (2016) Cardiac fibrosis: the fibroblast awakens. Circ Res 118:1021–1040

    Article  CAS  Google Scholar 

  • Wang X, Yong C, Yu K, Yu R, Zhang R, Yu L, Li S, Cai S (2018) Long noncoding RNA (lncRNA) n379519 promotes cardiac fibrosis in post-infarct myocardium by targeting miR-30. Med Sci Monit 24:3958–3965

    Article  CAS  Google Scholar 

  • Wang Y, Jin BJ, Chen Q, Yan BJ, Liu ZL (2019) MicroRNA-29b upregulation improves myocardial fibrosis and cardiac function in myocardial infarction rats through targeting SH2B3. Eur Rev Med Pharmacol Sci 23:10115–10122

    CAS  PubMed  Google Scholar 

  • White HD, Chew DP (2008) Acute myocardial infarction. Lancet 372:570–584

    Article  CAS  Google Scholar 

  • Yang D, Yu J, Liu HB, Yan XQ, Hu J, Yu Y, Guo J, Yuan Y, Du ZM (2019) The long non-coding RNA TUG1-miR-9a-5p axis contributes to ischemic injuries by promoting cardiomyocyte apoptosis via targeting KLF5. Cell Death Dis 10:908

    Article  CAS  Google Scholar 

  • Young TL, Matsuda T, Cepko CL (2005) The noncoding RNA taurine upregulated gene 1 is required for differentiation of the murine retina. Curr Biol 15:501–512

    Article  CAS  Google Scholar 

  • Yuan X, Pan J, Wen L, Gong B, Li J, Gao H, Tan W, Liang S, Zhang H, Wang X (2020) MiR-590-3p regulates proliferation, migration and collagen synthesis of cardiac fibroblast by targeting ZEB1. J Cell Mol Med 24:227–237

    Article  CAS  Google Scholar 

  • Zang XJ, Li L, Du X, Yang B, Mei CL (2019) LncRNA TUG1 inhibits the proliferation and fibrosis of mesangial cells in diabetic nephropathy via inhibiting the PI3K/AKT pathway. Eur Rev Med Pharmacol Sci 23:7519–7525

    PubMed  Google Scholar 

  • Zhong X, Chung AC, Chen HY, Meng XM, Lan HY (2011) Smad3-mediated upregulation of miR-21 promotes renal fibrosis. J Am Soc Nephrol 22:1668–1681

    Article  CAS  Google Scholar 

  • Zhou C, Cui Q, Su G, Guo X, Liu X, Zhang J (2016) MicroRNA-208b alleviates post-infarction myocardial fibrosis in a Rat model by inhibiting GATA4. Med Sci Monit 22:1808–1816

    Article  CAS  Google Scholar 

  • Zou X, Wang J, Tang L, Wen Q (2019) LncRNA TUG1 contributes to cardiac hypertrophy via regulating miR-29b-3p. In Vitro Cell Dev Biol Anim 55:482–490

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University.

Author information

Author notes

  1. Qingsong Sun and Man Luo are equal to this work.

Authors and Affiliations

  1. Department of Emergency, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, No.1, Huanghe West Road, Huaiyin District, Huai’an, 223300, Jiangsu, China

    Qingsong Sun, Man Luo, Zhiwei Gao, Xiang Han, Zhuan Yan, Shouxiang Xie, Hongmei Zhao & Hong Sun

Authors
  1. Qingsong Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Man Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhiwei Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiang Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhuan Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shouxiang Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hongmei Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hong Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Hongmei Zhao or Hong Sun.

Ethics declarations

Conflict of interest

All authors declare no conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sun, Q., Luo, M., Gao, Z. et al. TUG1 knockdown suppresses cardiac fibrosis after myocardial infarction. Mamm Genome 32, 435–442 (2021). https://doi.org/10.1007/s00335-021-09895-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00335-021-09895-z

Search

Navigation