CoChat
Sign Up
Cited by 133Cardiac Fibrosis and RemodelingHippo pathway signaling and YAP/TAZCongenital heart defects research

Blockade of Fibroblast YAP Attenuates Cardiac Fibrosis and Dysfunction Through MRTF-A Inhibition

Open access
Francisco, Jamie, Zhang, Yu, Jeong, Jae Im, Mizushima, Wataru, Ikeda, Shohei, Ivessa, Andreas, Oka, Shinichi, Zhai, Peiyong +2 more·2020·JACC: Basic to Translational Science
DOI 10.1016/j.jacbts.2020.07.009PMC PMC7524792
Open this paper in CoChat — free account

Abstract

Fibrotic remodeling of the heart in response to injury contributes to heart failure, yet therapies to treat fibrosis remain elusive. Yes-associated protein (YAP) is activated in cardiac fibroblasts by myocardial infarction, and genetic inhibition of fibroblast YAP attenuates myocardial infarction-induced cardiac dysfunction and fibrosis. YAP promotes myofibroblast differentiation and associated extracellular matrix gene expression through engagement of TEA domain transcription factor 1 and subsequent de novo expression of myocardin-related transcription factor A. Thus, fibroblast YAP is a promising therapeutic target to prevent fibrotic remodeling and heart failure.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.jacbts.2020.07.009

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • MRTcoF signalling plays an important role in complex physiological processes from early development to fibrosis.

    “MRTcoF signalling plays an important role in complex physiological processes from early development to fibrosis [14, 15, 16].”

    From Mechanical stiffness orchestrates distinct regulation of <scp>MRTFs</scp> and <scp>YAP</scp> / <scp>TAZ</scp> transcriptional cofactors in hepatocytes (2026) · cites this paper as [15]

    The Discussion identifies RhoA–MRTF–SRF signaling as a pathway that modulates cardiac fibrosis, and the Results show a role for MRTF-A in pro-fibrotic responses in cardiac fibroblasts. Our copy does not address a role in early development or establish the claimed range of physiological processes. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 33

  1. [1]Prabhu S.D. Frangogiannis N.G. The biological basis for cardiac repair after myocardial infarction: from inflammation to fibrosis Circ Res 119 2016 91 112 27340270 PMC4922528
  2. [2]Kanisicak O. Khalil H. Ivey M.J. Genetic lineage tracing defines myofibroblast origin and function in the injured heart Nat Commun 7 2016 12260 27447449 PMC5512625
  3. [3]Ivey M.J. Kuwabara J.T. Pai J.T. Moore R.E. Sun Z. Tallquist M.D. Resident fibroblast expansion during cardiac growth and remodeling J Molec Cellular Cardiol 114 2018 161 174 29158033 PMC5831691
  4. [4]Shimazaki M. Nakamura K. Kii I. Periostin is essential for cardiac healing after acute myocardial infarction J Exp Med 205 2008 295 303 18208976 PMC2271007
  5. [7]Matsuda T. Zhai P. Sciarretta S. NF2 activates Hippo signaling and promotes ischemia/reperfusion injury in the heart Circ Res 119 2016 596 606 27402866 PMC4992450
  6. [8]Shao D. Zhai P. Del Re D.P. A functional interaction between Hippo-YAP signalling and FoxO1 mediates the oxidative stress response Nat Commun 5 2014 3315 24525530 PMC3962829
  7. [9]Lin Z. von Gise A. Zhou P. Cardiac-specific YAP activation improves cardiac function and survival in an experimental murine myocardial infarction model Circ Res 115 2014 354 363 24833660 PMC4104149
  8. [10]Leach J.P. Heallen T. Zhang M. Hippo pathway deficiency reverses systolic heart failure after infarction Nature 550 2017 260 264 28976966 PMC5729743
  9. [12]Xin M. Kim Y. Sutherland L.B. Hippo pathway effector Yap promotes cardiac regeneration Proc Natl Acad Sci U S A 110 2013 13839 13844 23918388 PMC3752208
  10. [13]Zhang N. Bai H. David K.K. The Merlin/NF2 tumor suppressor functions through the YAP oncoprotein to regulate tissue homeostasis in mammals Dev Cell 19 2010 27 38 20643348 PMC2925178
  11. [14]Acharya A. Baek S.T. Banfi S. Eskiocak B. Tallquist M.D. Efficient inducible Cre-mediated recombination in Tcf21 cell lineages in the heart and kidney Genesis 49 2011 870 877 21432986 PMC3279154
  12. [15]Kim J.E. Nakashima K. de Crombrugghe B. Transgenic mice expressing a ligand-inducible cre recombinase in osteoblasts and odontoblasts: a new tool to examine physiology and disease of postnatal bone and tooth Am J Pathol 165 2004 1875 1882 15579432 PMC1618706
  13. [16]Molkentin J.D. Bugg D. Ghearing N. Fibroblast-specific genetic manipulation of p38 mitogen-activated protein kinase in vivo reveals its central regulatory role in fibrosis Circulation 136 2017 549 561 28356446 PMC5548661
  14. [17]Jonsson M.K.B. Hartman R.J.G. Ackers-Johnson M. A transcriptomic and epigenomic comparison of fetal and adult human cardiac fibroblasts reveals novel key transcription factors in adult cardiac fibroblasts J Am Coll Cardiol Basic Trans Science 1 2016 590 602 PMC6113540 30167544
  15. [18]Small E.M. Thatcher J.E. Sutherland L.B. Myocardin-related transcription factor-a controls myofibroblast activation and fibrosis in response to myocardial infarction Circ Res 107 2010 294 304 20558820 PMC2921870
  16. [19]Yu O.M. Miyamoto S. Brown J.H. Myocardin-related transcription factor A and yes-associated protein exert dual control in G protein-coupled receptor- and RhoA-mediated transcriptional regulation and cell proliferation Mol Cell Biol 36 2015 39 49 26459764 PMC4702594
  17. [20]Haak A.J. Tsou P.S. Amin M.A. Targeting the myofibroblast genetic switch: inhibitors of myocardin-related transcription factor/serum response factor-regulated gene transcription prevent fibrosis in a murine model of skin injury J Pharmacol Exp Ther 349 2014 480 486 24706986 PMC4019321
  18. [21]Abe H. Takeda N. Isagawa T. Macrophage hypoxia signaling regulates cardiac fibrosis via Oncostatin M Nat Commun 10 2019 2824 31249305 PMC6597788
  19. [22]Liu F. Lagares D. Choi K.M. Mechanosignaling through YAP and TAZ drives fibroblast activation and fibrosis Am J Physiol Lung Cell Mol Physiol 308 2015 L344 L357 25502501 PMC4329470
  20. [24]Liang M. Yu M. Xia R. Yap/Taz deletion in Gli(+) cell-derived myofibroblasts attenuates fibrosis J Am Soc Nephrol 28 2017 3278 3290 28768710 PMC5661271
  21. [25]Xiao Y. Hill M.C. Li L. Hippo pathway deletion in adult resting cardiac fibroblasts initiates a cell state transition with spontaneous and self-sustaining fibrosis Genes Dev 33 2019 1491 1505 31558567 PMC6824468
  22. [26]Khalil H. Kanisicak O. Prasad V. Fibroblast-specific TGF-beta-Smad2/3 signaling underlies cardiac fibrosis J Clin Invest 127 2017 3770 3783 28891814 PMC5617658
  23. [27]Davis J. Burr A.R. Davis G.F. Birnbaumer L. Molkentin J.D. A TRPC6-dependent pathway for myofibroblast transdifferentiation and wound healing in vivo Dev Cell 23 2012 705 715 23022034 PMC3505601
  24. [28]Davis J. Salomonis N. Ghearing N. MBNL1-mediated regulation of differentiation RNAs promotes myofibroblast transformation and the fibrotic response Nat Commun 6 2015 10084 26670661 PMC4703843
  25. [29]Wang D.Z. Li S. Hockemeyer D. Potentiation of serum response factor activity by a family of myocardin-related transcription factors Proc Natl Acad Sci U S A 99 2002 14855 14860 12397177 PMC137508
  26. [30]Miralles F. Posern G. Zaromytidou A.I. Treisman R. Actin dynamics control SRF activity by regulation of its coactivator MAL Cell 113 2003 329 342 12732141
  27. [31]Zhao X. Ding E.Y. Yu O.M. Induction of the matricellular protein CCN1 through RhoA and MRTF-A contributes to ischemic cardioprotection J Molec Cellular Cardiol 75 2014 152 161 25106095 PMC4157956
  28. [32]Foster C.T. Gualdrini F. Treisman R. Mutual dependence of the MRTF-SRF and YAP-TEAD pathways in cancer-associated fibroblasts is indirect and mediated by cytoskeletal dynamics Genes Dev 31 2017 2361 2375 29317486 PMC5795783
  29. [33]Liao X.H. Wang N. Liu Q.X. Myocardin-related transcription factor-A induces cardiomyocyte hypertrophy IUBMB Life 63 2011 54 61 21280178
  30. [34]Hiemer S.E. Szymaniak A.D. Varelas X. The transcriptional regulators TAZ and YAP direct transforming growth factor beta-induced tumorigenic phenotypes in breast cancer cells J Biol Chem 289 2014 13461 13474 24648515 PMC4036353
  31. [35]Lauriol J. Keith K. Jaffre F. RhoA signaling in cardiomyocytes protects against stress-induced heart failure but facilitates cardiac fibrosis Sci Signal 7 2014 ra100 25336613 PMC4300109
  32. [36]Lindsey M.L. Bolli R. Canty J.M. Guidelines for experimental models of myocardial ischemia and infarction Am J Physiol Heart Circ Physiol 314 4 2018 H812 H838 29351451 PMC5966768
  33. [37]Murphy E. Steenbergen C. Gender-based differences in mechanisms of protection in myocardial ischemia-reperfusion injury Cardiovasc Res 75 2007 478 486 17466956

Cited by

Sorted by citations

Authors
Francisco, J., Zhang, Y., Jeong, J. I., Mizushima, W., Ikeda, S., Ivessa, A., Oka, S., Zhai, P., Tallquist, M. D., & Del Re, D. P.
Affiliations
  • Rutgers New Jersey Medical School (US)
  • University of Hawaiʻi at Mānoa (US)
ORCID
Venue
JACC: Basic to Translational Science
Publisher
Elsevier BV
Published
2020-09
Volume
5
Issue
9
Pages
931-945
ISSN
2452-302X (ISSN-L)
DOI
10.1016/j.jacbts.2020.07.009
PMC
PMC7524792
OpenAlex
W3091295206
Cited by
133
References
4
Citations by year
2026: 20 · 2025: 16 · 2024: 25 · 2023: 21 · 2022: 30 · 2021: 19 · 2020: 2
FWCI
11.14
Type
journal article
Language
en
Update notices
erratum (2021-07-01)
Open access
Licence
Locations
  • JACC Basic to Translational Science (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
National Institutes of Health (HL127339, HL135726)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
Keywords
YAP, myocardial fibrosis, cardiac fibroblasts, MRTF-A, TEAD1, myofibroblast differentiation, extracellular matrix, myocardial infarction, heart failure, cardiac remodeling, heart failure treatment

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review