Acute contact with profibrotic macrophages mechanically activates fibroblasts via αvβ3 integrin-mediated engagement of Piezo1.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101653440 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2375-2548 (Electronic) Linking ISSN: 23752548 NLM ISO Abbreviation: Sci Adv Subsets: MEDLINE
    • Publication Information:
      Original Publication: Washington, DC : American Association for the Advancement of Science, [2015]-
    • Subject Terms:
      Fibroblasts*/metabolism ; Macrophages*/metabolism ; Integrin alphaVbeta3*/metabolism ; Mechanotransduction, Cellular* ; Ion Channels*/metabolism; Animals ; Mice ; Fibrosis ; Humans ; Calcium/metabolism ; Extracellular Matrix/metabolism ; Stress, Mechanical
    • Abstract:
      Fibrosis-excessive scarring after injury-causes >40% of disease-related deaths worldwide. In this misguided repair process, activated fibroblasts drive the destruction of organ architecture by accumulating and contracting extracellular matrix. The resulting stiff scar tissue, in turn, enhances fibroblast contraction-bearing the question of how this positive feedback loop begins. We show that direct contact with profibrotic but not proinflammatory macrophages triggers acute fibroblast contractions. The contractile response depends on αvβ3 integrin expression on macrophages and Piezo1 expression on fibroblasts. The touch of macrophages elevates fibroblast cytosolic calcium within seconds, followed by translocation of the transcription cofactors nuclear factor of activated T cells 1 and Yes-associated protein, which drive fibroblast activation within hours. Intriguingly, macrophages induce mechanical stress in fibroblasts on soft matrix that alone suppresses their spontaneous activation. We propose that acute contact with suitable macrophages mechanically kick-starts fibroblast activation in an otherwise nonpermissive soft environment. The molecular components mediating macrophage-fibroblast mechanotransduction are potential targets for antifibrosis strategies.
    • References:
      Cell. 2017 Nov 30;171(6):1397-1410.e14. (PMID: 29107331)
      Sci Signal. 2019 Jan 15;12(564):. (PMID: 30647145)
      Immunity. 2016 Mar 15;44(3):450-462. (PMID: 26982353)
      Matrix Biol. 2021 Mar;97:58-71. (PMID: 33508427)
      Wound Repair Regen. 2017 May;25(3):377-388. (PMID: 28370945)
      Eur Biophys J. 2016 May;45(4):301-9. (PMID: 26613613)
      Exp Cell Res. 1983 Oct;148(1):117-26. (PMID: 6605252)
      Front Physiol. 2020 Feb 14;11:89. (PMID: 32116794)
      Am J Respir Cell Mol Biol. 2020 Apr;62(4):479-492. (PMID: 31944822)
      Cell. 2017 Apr 20;169(3):510-522.e20. (PMID: 28431249)
      Mol Biol Cell. 2001 Sep;12(9):2730-41. (PMID: 11553712)
      Science. 2017 Jun 9;356(6342):1026-1030. (PMID: 28596335)
      Am J Respir Cell Mol Biol. 2019 Jun;60(6):609-610. (PMID: 30653923)
      Respir Res. 2006 Sep 27;7:122. (PMID: 17005044)
      Biophys J. 2008 Jan 1;94(1):207-20. (PMID: 17827246)
      Semin Cell Dev Biol. 2020 May;101:123-139. (PMID: 31879265)
      Elife. 2019 Feb 08;8:. (PMID: 30735126)
      JCI Insight. 2019 Apr 16;5:. (PMID: 30990466)
      JCI Insight. 2022 Feb 22;7(4):. (PMID: 35191398)
      Genome Biol. 2007;8(5):215. (PMID: 17543136)
      Nat Biomed Eng. 2021 Dec;5(12):1437-1456. (PMID: 34031559)
      Pharmacol Ther. 2023 Oct;250:108528. (PMID: 37708995)
      Nat Commun. 2019 Apr 23;10(1):1850. (PMID: 31015429)
      J Clin Invest. 2014 Dec;124(12):5225-38. (PMID: 25365224)
      Nat Commun. 2016 Aug 18;7:12502. (PMID: 27535340)
      Sci Adv. 2024 Mar 15;10(11):eadk6906. (PMID: 38478620)
      Int J Mol Sci. 2021 Jan 30;22(3):. (PMID: 33573367)
      Nature. 2011 Jun 08;474(7350):179-83. (PMID: 21654799)
      J Phys Condens Matter. 2010 May 19;22(19):194110. (PMID: 20458358)
      Am J Respir Crit Care Med. 2011 Sep 1;184(5):569-81. (PMID: 21680953)
      Am J Respir Cell Mol Biol. 2017 May;56(5):667-679. (PMID: 28459387)
      Cell Death Dis. 2019 May 24;10(6):401. (PMID: 31127093)
      J Cell Biol. 1996 Jul;134(1):67-80. (PMID: 8698823)
      Methods Enzymol. 2012;504:183-200. (PMID: 22264535)
      Nat Rev Mol Cell Biol. 2024 Aug;25(8):617-638. (PMID: 38589640)
      Front Immunol. 2020 Dec 14;11:570195. (PMID: 33381111)
      Sci Adv. 2024 Mar 29;10(13):eadj9559. (PMID: 38552026)
      J Immunol. 2022 Nov 15;209(10):1999-2011. (PMID: 36426946)
      J Am Soc Nephrol. 2016 Oct;27(10):3117-3128. (PMID: 26961347)
      Nature. 2013 Jul 18;499(7458):295-300. (PMID: 23868258)
      Exp Cell Res. 2010 Sep 10;316(15):2390-401. (PMID: 20451515)
      Adv Healthc Mater. 2019 Feb;8(4):e1801451. (PMID: 30658015)
      J Cell Biol. 2010 Aug 23;190(4):693-706. (PMID: 20733059)
      J Invest Dermatol. 2014 Jul;134(7):1862-1872. (PMID: 24670384)
      Stem Cells. 2021 Sep;39(9):1145-1154. (PMID: 33786935)
      Sci Rep. 2021 Aug 18;11(1):16975. (PMID: 34408164)
      Nat Commun. 2018 Nov 23;9(1):4966. (PMID: 30470756)
      Nat Med. 2014 Aug;20(8):857-69. (PMID: 25100531)
      Science. 2010 Oct 1;330(6000):55-60. (PMID: 20813920)
      Sci Signal. 2019 Nov 12;12(607):. (PMID: 31719171)
      Sci Transl Med. 2019 Oct 30;11(516):. (PMID: 31666402)
      J Clin Invest. 2018 Jan 2;128(1):74-84. (PMID: 29293092)
      Cell Death Dis. 2021 Mar 1;12(3):226. (PMID: 33649312)
      Int J Exp Pathol. 2012 Aug;93(4):243-51. (PMID: 22774768)
      Cold Spring Harb Perspect Biol. 2023 Jan 3;15(1):. (PMID: 36123034)
      Am J Pathol. 2023 Sep;193(9):1208-1222. (PMID: 37328100)
      Cell Motil Cytoskeleton. 2006 Jun;63(6):321-40. (PMID: 16634082)
      Am J Pathol. 2022 May;192(5):750-761. (PMID: 35183510)
      Nat Biomed Eng. 2018 Feb;2(2):124-137. (PMID: 31015629)
      Cell. 2023 Sep 14;186(19):4007-4037. (PMID: 37714133)
      J Clin Invest. 2006 Dec;116(12):3114-26. (PMID: 17099778)
      Front Cell Dev Biol. 2021 Nov 05;9:741060. (PMID: 34805150)
      Mol Biol Cell. 2004 Sep;15(9):4310-20. (PMID: 15240821)
      J Cell Biol. 2006 Jan 16;172(2):259-68. (PMID: 16401722)
      Matrix Biol. 2018 Nov;73:64-76. (PMID: 29274939)
      Front Immunol. 2022 May 12;13:880887. (PMID: 35634278)
      J Clin Invest. 2005 Jan;115(1):56-65. (PMID: 15630444)
      Cell. 2018 Feb 8;172(4):744-757.e17. (PMID: 29398113)
      Exp Cell Res. 2000 Feb 1;254(2):210-20. (PMID: 10640419)
      J Cell Sci. 2008 Oct 15;121(Pt 20):3305-16. (PMID: 18827018)
      Front Immunol. 2022 May 17;13:875407. (PMID: 35664010)
      Acta Biomater. 2019 Apr 15;89:47-59. (PMID: 30826478)
      Cells. 2022 Apr 02;11(7):. (PMID: 35406763)
      J Clin Invest. 2023 Jul 17;133(14):. (PMID: 37463440)
      Am J Physiol Lung Cell Mol Physiol. 2012 Jul 1;303(1):L12-9. (PMID: 22561460)
      J Cell Biol. 2003 Oct 13;163(1):119-29. (PMID: 14557251)
      Annu Rev Pathol. 2022 Jan 24;17:515-546. (PMID: 34813355)
      Sci Adv. 2022 Nov 11;8(45):eabo1461. (PMID: 36351022)
      Exp Cell Res. 1999 Aug 25;251(1):234-43. (PMID: 10438589)
      J Biol Chem. 2019 Nov 15;294(46):17395-17408. (PMID: 31586031)
      Commun Biol. 2019 Aug 7;2:298. (PMID: 31396578)
      Dev Cell. 2012 Oct 16;23(4):705-15. (PMID: 23022034)
    • Accession Number:
      0 (Integrin alphaVbeta3)
      0 (Ion Channels)
      0 (Piezo1 protein, mouse)
      0 (PIEZO1 protein, human)
      SY7Q814VUP (Calcium)
    • Publication Date:
      Date Created: 20241023 Date Completed: 20241023 Latest Revision: 20241031
    • Publication Date:
      20241031
    • Accession Number:
      PMC11498225
    • Accession Number:
      10.1126/sciadv.adp4726
    • Accession Number:
      39441936