Display options
Cite
Shi-Wen X, Racanelli M, Ali A, et al. Verteporfin inhibits the persistent fibrotic phenotype of lesional scleroderma dermal fibroblasts. J Cell Commun Signal. 2021;15(1):71-80doi: 10.1007/s12079-020-00596-x.
Shi-Wen, X., Racanelli, M., Ali, A., Simon, A., Quesnel, K., Stratton, R. J., & Leask, A. (2021). Verteporfin inhibits the persistent fibrotic phenotype of lesional scleroderma dermal fibroblasts. Journal of cell communication and signaling, 15(1), 71-80. https://doi.org/10.1007/s12079-020-00596-x
Shi-Wen, Xu, et al. "Verteporfin inhibits the persistent fibrotic phenotype of lesional scleroderma dermal fibroblasts." Journal of cell communication and signaling vol. 15,1 (2021): 71-80. doi: https://doi.org/10.1007/s12079-020-00596-x
Shi-Wen X, Racanelli M, Ali A, Simon A, Quesnel K, Stratton RJ, Leask A. Verteporfin inhibits the persistent fibrotic phenotype of lesional scleroderma dermal fibroblasts. J Cell Commun Signal. 2021 Mar;15(1):71-80. doi: 10.1007/s12079-020-00596-x. Epub 2021 Jan 04. PMID: 33398723; PMCID: PMC7905010.
Copy Download .nbib Format: NLM
Share it on

J Cell Commun Signal. 2021 Mar;15(1):71-80. doi: 10.1007/s12079-020-00596-x. Epub 2021 Jan 04.

Verteporfin inhibits the persistent fibrotic phenotype of lesional scleroderma dermal fibroblasts.

Journal of cell communication and signaling

Xu Shi-Wen, Michael Racanelli, Aaisham Ali, Amara Simon, Katherine Quesnel, Richard J Stratton, Andrew Leask

Affiliations

  1. UCL Division of Medicine, Centre for Rheumatology, University College London, Royal Free Campus, Rowland Hill St, London, NW3 2PF, UK.
  2. Department of Physiology and Pharmacology, University of Western Ontario, London, ON, N6A 5C1, Canada.
  3. School of Dentistry, University of Western Ontario, London, ON, N6A 5C1, Canada.
  4. College of Dentistry, University of Saskatchewan, 105 Wiggins Rd, Saskatoon, SK, S7N 5E4, Canada. [email protected].

PMID: 33398723 PMCID: PMC7905010 DOI: 10.1007/s12079-020-00596-x

Abstract

Fibrosis is perpetuated by an autocrine, pro-adhesive signaling loop maintained by the synthetic and contractile abilities of myofibroblasts and the stiff, highly-crosslinked extracellular matrix. Transcriptional complexes that are exquisitely responsive to mechanotransduction include the co-activator YAP1, which regulates the expression of members of the CCN family of matricellular proteins such as CCN2 and CCN1. Although selective YAP1 inhibitors exist, the effect of these inhibitors on profibrotic gene expression in fibroblasts is largely unknown, and is the subject of our current study. Herein, we use genome-wide expression profiling, real-time polymerase chain reaction and Western blot analyses, cell migration and collagen gel contraction assays to assess the ability of a selective YAP inhibitor verteporfin (VP) to block fibrogenic activities in dermal fibroblasts from healthy individual human controls and those from isolated from fibrotic lesions of patients with diffuse cutaneous systemic sclerosis (dcSSc). In control fibroblasts, VP selectively reduced expression of fibrogenic genes and also blocked the ability of TGFbeta to induce actin stress fibers in dermal fibroblasts. VP also reduced the persistent profibrotic phenotype of dermal fibroblasts cultured from fibrotic lesions of patients with dcSSc. Our results are consistent with the notion that, in the future, YAP1 inhibitors may represent a novel, valuable method of treating fibrosis as seen in dcSSc.

Keywords: CCN2; CTGF; Connective tissue growth factor; Fibrosis; Mechanotransduction; Myofibroblasr; Scleroderma; Verteporfin; YAP1

References

  1. Cytokine Growth Factor Rev. 2004 Aug;15(4):255-73 - PubMed
  2. Mol Pharm. 2019 Mar 4;16(3):1009-1024 - PubMed
  3. Am J Physiol Cell Physiol. 2020 Jun 1;318(6):C1046-C1054 - PubMed
  4. Onco Targets Ther. 2016 Aug 29;9:5371-81 - PubMed
  5. Adv Wound Care (New Rochelle). 2013 May;2(4):160-166 - PubMed
  6. Arthritis Rheum. 2009 Sep;60(9):2817-21 - PubMed
  7. Arthritis Rheum. 2013 Nov;65(11):2737-47 - PubMed
  8. Cancer Sci. 2019 Feb;110(2):561-567 - PubMed
  9. Nat Rev Mol Cell Biol. 2002 May;3(5):349-63 - PubMed
  10. Exp Cell Res. 2019 Jun 1;379(1):119-128 - PubMed
  11. Matrix Biol Plus. 2019 Jul 06;3:100009 - PubMed
  12. J Wound Care. 2013 Aug;22(8):407-8, 410-12 - PubMed
  13. Hum Reprod. 2019 Mar 1;34(3):506-518 - PubMed
  14. Am J Cancer Res. 2015 Dec 15;6(1):27-37 - PubMed
  15. Nat Rev Dis Primers. 2015 Apr 23;1:15002 - PubMed
  16. J Cell Commun Signal. 2020 Mar;14(1):21-29 - PubMed
  17. Rheumatology (Oxford). 2012 Dec;51(12):2146-54 - PubMed
  18. Arthritis Res Ther. 2017 Jun 13;19(1):134 - PubMed
  19. PLoS One. 2019 Jun 6;14(6):e0218178 - PubMed
  20. J Invest Dermatol. 2018 Jan;138(1):78-88 - PubMed
  21. Front Med (Lausanne). 2015 Sep 03;2:59 - PubMed
  22. PLoS One. 2009 Oct 13;4(10):e7438 - PubMed
  23. Curr Opin Pharmacol. 2016 Aug;29:26-33 - PubMed
  24. Arthritis Rheum. 2012 May;64(5):1653-64 - PubMed
  25. Matrix Biol. 2018 Aug;68-69:522-532 - PubMed
  26. J Biol Chem. 2003 Apr 4;278(14):12384-9 - PubMed
  27. PLoS One. 2017 Oct 19;12(10):e0186740 - PubMed
  28. PLoS One. 2011;6(5):e19756 - PubMed
  29. Biochim Biophys Acta. 2013 Jul;1832(7):1049-60 - PubMed
  30. Arthritis Rheum. 2013 Nov;65(11):2940-4 - PubMed
  31. Wound Repair Regen. 2014 Jan-Feb;22(1):119-24 - PubMed
  32. Genes Dev. 2012 Jun 15;26(12):1300-5 - PubMed
  33. J Invest Dermatol. 2011 Oct;131(10):1996-2003 - PubMed
  34. Am J Pathol. 2020 Jan;190(1):206-221 - PubMed
  35. Mol Biol Cell. 2007 Jun;18(6):2169-78 - PubMed
  36. J Biol Chem. 2003 Apr 11;278(15):13008-15 - PubMed
  37. Curr Med Chem. 2016;23(11):1171-84 - PubMed

Publication Types