Item request has been placed! ×
Item request cannot be made. ×
loading  Processing Request

Receptor activity-modifying protein 1 regulates mouse skin fibroblast proliferation via the Gαi3-PKA-CREB-YAP axis.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read Online Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: BioMed Central Country of Publication: England NLM ID: 101170464 Publication Model: Electronic Cited Medium: Internet ISSN: 1478-811X (Electronic) Linking ISSN: 1478811X NLM ISO Abbreviation: Cell Commun Signal Subsets: MEDLINE
    • Publication Information:
      Original Publication: [London] : BioMed Central, c2003-
    • Subject Terms:
      Cyclic AMP-Dependent Protein Kinases*/metabolism ; GTP-Binding Protein alpha Subunits, Gi-Go*/metabolism ; Receptor Activity-Modifying Protein 1*/genetics ; Receptor Activity-Modifying Protein 1*/metabolism ; Signal Transduction* ; Skin*/cytology ; Skin*/metabolism ; YAP-Signaling Proteins*/metabolism; Animals ; Cell Proliferation ; Cyclic AMP Response Element-Binding Protein/metabolism ; Fibroblasts/cytology ; Fibroblasts/metabolism ; Mice
    • Abstract:
      Background: Skin innervation is crucial for normal wound healing. However, the relationship between nerve receptors and wound healing and the intrinsic mechanism remains to be further identified. In this study, we investigated the role of a calcitonin gene-related peptide (CGRP) receptor component, receptor activity-modifying protein 1 (RAMP1), in mouse skin fibroblast (MSF) proliferation.
      Methods: In vivo, Western blotting and immunohistochemical (IHC) staining of mouse skin wounds tissue was used to detect changes in RAMP1 expression. In vitro, RAMP1 was overexpressed in MSF cell lines by infection with Tet-On-Flag-RAMP1 lentivirus and doxycycline (DOX) induction. An IncuCyte S3 Live-Cell Analysis System was used to assess and compare the proliferation rate differences between different treatment groups. Total protein and subcellular extraction Western blot analysis, quantitative real-time-polymerase chain reaction (qPCR) analysis, and immunofluorescence (IF) staining analysis were conducted to detect signalling molecule expression and/or distribution. The CUT & RUN assay and dual-luciferase reporter assay were applied to measure protein-DNA interactions.
      Results: RAMP1 expression levels were altered during skin wound healing in mice. RAMP1 overexpression promoted MSF proliferation. Mechanistically, total Yes-associated protein (YAP) and nuclear YAP protein expression was increased in RAMP1-overexpressing MSFs. RAMP1 overexpression increased inhibitory guanine nucleotide-binding protein (G protein) α subunit 3 (Gαi3) expression and activated downstream protein kinase A (PKA), and both elevated the expression of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) and activated it, promoting the transcription of YAP, elevating the total YAP level and promoting MSF proliferation.
      Conclusions: Based on these data, we report, for the first time, that changes in the total RAMP1 levels during wound healing and RAMP1 overexpression alone can promote MSF proliferation via the Gαi3-PKA-CREB-YAP axis, a finding critical for understanding RAMP1 function, suggesting that this pathway is an attractive and accurate nerve target for skin wound treatment. Video Abstract.
      (© 2022. The Author(s).)
    • References:
      Cell Mol Life Sci. 2020 Oct;77(20):4049-4067. (PMID: 32347317)
      Mol Neurobiol. 2018 Feb;55(2):1236-1243. (PMID: 28110472)
      Trends Pharmacol Sci. 2018 Apr;39(4):367-386. (PMID: 29395118)
      J Biol Chem. 2000 Oct 6;275(40):31438-43. (PMID: 10903324)
      Nat Cell Biol. 2019 Jan;21(1):18-24. (PMID: 30602767)
      Nat Commun. 2017 Mar 23;8:14744. (PMID: 28332498)
      Trends Pharmacol Sci. 2020 Apr;41(4):249-265. (PMID: 32115276)
      Hepatology. 2013 Sep;58(3):1011-20. (PMID: 23532963)
      Arch Dermatol Res. 2018 Nov;310(9):737-750. (PMID: 30209580)
      Cell Signal. 2004 Nov;16(11):1211-27. (PMID: 15337521)
      Trends Cell Biol. 2018 Sep;28(9):709-722. (PMID: 29807713)
      Cell Tissue Res. 2020 Jan;379(1):181-193. (PMID: 31768712)
      Trends Pharmacol Sci. 2010 Oct;31(10):476-83. (PMID: 20633935)
      Crit Rev Biochem Mol Biol. 2016;51(1):65-71. (PMID: 26740457)
      Mol Cancer Res. 2013 Nov;11(11):1462-77. (PMID: 24025972)
      Wound Repair Regen. 2013 Nov-Dec;21(6):772-88. (PMID: 24134750)
      Nature. 1987 Jul 9-15;328(6126):175-8. (PMID: 2885756)
      FASEB J. 2020 Jun;34(6):8125-8138. (PMID: 32329113)
      Genes Dev. 2013 Jun 1;27(11):1223-32. (PMID: 23752589)
      J Dermatol Sci. 2014 Jun;74(3):193-203. (PMID: 24630238)
      J Surg Res. 2017 Nov;219:50-60. (PMID: 29078910)
      Am J Cancer Res. 2015 Dec 15;6(1):27-37. (PMID: 27073720)
      Semin Immunopathol. 2018 May;40(3):249-259. (PMID: 29713744)
      J Plast Surg Hand Surg. 2014 Apr;48(2):143-7. (PMID: 24006918)
      Nature. 2008 May 15;453(7193):314-21. (PMID: 18480812)
      Semin Cell Dev Biol. 2004 Jun;15(3):299-308. (PMID: 15125893)
      Physiol Rev. 2019 Jan 1;99(1):665-706. (PMID: 30475656)
      Biomed Pharmacother. 2008 Jul-Aug;62(6):352-9. (PMID: 18430544)
      Adv Wound Care (New Rochelle). 2016 Mar 1;5(3):119-136. (PMID: 26989578)
      Cells. 2019 May 08;8(5):. (PMID: 31072060)
      Acta Derm Venereol. 2016 Jun 15;96(5):587-94. (PMID: 26676806)
      Cell Rep. 2019 Nov 19;29(8):2154-2163.e5. (PMID: 31747590)
      Br J Pharmacol. 2013 Feb;168(4):822-34. (PMID: 22946657)
      Genes Dev. 2010 Jan 1;24(1):72-85. (PMID: 20048001)
      Physiol Rev. 2014 Oct;94(4):1099-142. (PMID: 25287861)
      Nature. 1983 Jul 14-20;304(5922):129-35. (PMID: 6346105)
      Cell Tissue Res. 2018 Feb;371(2):273-282. (PMID: 29150821)
      Hepatology. 2012 Dec;56(6):2051-9. (PMID: 22707013)
      Genes Dev. 2007 Nov 1;21(21):2747-61. (PMID: 17974916)
      Histol Histopathol. 2015 Aug;30(8):875-92. (PMID: 25799052)
      Surg Clin North Am. 2010 Dec;90(6):1133-46. (PMID: 21074032)
      J Neurosci. 1999 Jan 1;19(1):180-92. (PMID: 9870949)
      EMBO J. 2013 May 29;32(11):1543-55. (PMID: 23644383)
      Semin Immunopathol. 2018 May;40(3):229-236. (PMID: 29616309)
      Exp Dermatol. 2012 Feb;21(2):156-8. (PMID: 22229444)
      Exp Cell Res. 2019 Oct 1;383(1):111504. (PMID: 31325438)
      Proc Natl Acad Sci U S A. 2004 Dec 21;101(51):17622-7. (PMID: 15585582)
      Pharmacol Ther. 2006 Jan;109(1-2):173-97. (PMID: 16111761)
      Cell. 2015 Nov 5;163(4):811-28. (PMID: 26544935)
      Curr Biol. 1997 Apr 1;7(4):261-9. (PMID: 9094314)
      J Biol Chem. 2015 Sep 18;290(38):23009-22. (PMID: 26198634)
      J Invest Dermatol. 2013 Jun;133(6):1620-8. (PMID: 23283070)
      FASEB J. 2014 Mar;28(3):1237-47. (PMID: 24308973)
      Cells. 2019 May 03;8(5):. (PMID: 31058846)
      Cytokine. 2015 May;73(1):144-55. (PMID: 25748837)
    • Contributed Indexing:
      Keywords: CREB; Fibroblast proliferation; PKA; RAMP1; Transcription factor; Wound healing; YAP
    • Accession Number:
      0 (Creb1 protein, mouse)
      0 (Cyclic AMP Response Element-Binding Protein)
      0 (Ramp1 protein, mouse)
      0 (Receptor Activity-Modifying Protein 1)
      0 (YAP-Signaling Proteins)
      0 (Yap1 protein, mouse)
      EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
      EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gi-Go)
      EC 3.6.5.1 (Gnai3 protein, mouse)
    • Publication Date:
      Date Created: 20220413 Date Completed: 20220414 Latest Revision: 20220614
    • Publication Date:
      20250114
    • Accession Number:
      PMC9004193
    • Accession Number:
      10.1186/s12964-022-00852-0
    • Accession Number:
      35413847