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Endoglin Is an Endothelial Housekeeper against Inflammation: Insight in ECFC-Related Permeability through LIMK/Cofilin Pathway.

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  • معلومة اضافية
    • المصدر:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: Basel, Switzerland : MDPI, [2000-
    • الموضوع:
      Cell Membrane Permeability*; Actin Depolymerizing Factors/*metabolism ; Endoglin/*metabolism ; Endothelial Cells/*pathology ; Inflammation/*pathology ; Lim Kinases/*metabolism ; Neovascularization, Pathologic/*pathology; Actin Depolymerizing Factors/genetics ; Animals ; Endoglin/genetics ; Endothelial Cells/metabolism ; Inflammation/genetics ; Inflammation/metabolism ; Lim Kinases/genetics ; Mice ; Neovascularization, Pathologic/genetics ; Neovascularization, Pathologic/metabolism
    • نبذة مختصرة :
      Endoglin (Eng) is an endothelial cell (EC) transmembrane glycoprotein involved in adhesion and angiogenesis. Eng mutations result in vessel abnormalities as observed in hereditary hemorrhagic telangiectasia of type 1. The role of Eng was investigated in endothelial functions and permeability under inflammatory conditions, focusing on the actin dynamic signaling pathway. Endothelial Colony-Forming Cells (ECFC) from human cord blood and mouse lung/aortic EC (MLEC, MAEC) from Eng +/+ and Eng +/- mice were used. ECFC silenced for Eng with Eng-siRNA and ctr-siRNA were used to test tubulogenesis and permeability +/- TNFα and +/- LIM kinase inhibitors (LIMKi). In silico modeling of TNFα-Eng interactions was carried out from PDB IDs 5HZW and 5HZV. Calcium ions (Ca 2+ ) flux was studied by Oregon Green 488 in epifluorescence microscopy. Levels of cofilin phosphorylation and tubulin post-translational modifications were evaluated by Western blot. F-actin and actin-tubulin distribution/co-localization were evaluated in cells by confocal microscopy. Eng silencing in ECFCs resulted in a decrease of cell sprouting by 50 ± 15% ( p < 0.05) and an increase in pseudo-tube width (41 ± 4.5%; p < 0.001) compared to control. Upon TNFα stimulation, ECFC Eng-siRNA displayed a significant higher permeability compared to ctr-siRNA ( p < 0.01), which is associated to a higher Ca 2+ mobilization ( p < 0.01). Computational analysis suggested that Eng mitigated TNFα activity. F-actin polymerization was significantly increased in ECFC Eng-siRNA, MAEC +/- , and MLEC +/- compared to controls ( p < 0.001, p < 0.01, and p < 0.01, respectively) as well as actin/tubulin distribution ( p < 0.01). Furthermore, the inactive form of cofilin (P-cofilin at Ser3) was significantly decreased by 36.7 ± 4.8% in ECFC Eng-siRNA compared to ctr-siRNA ( p < 0.001). Interestingly, LIMKi reproduced the absence of Eng on TNFα-induced ECFC-increased permeability. Our data suggest that Eng plays a critical role in the homeostasis regulation of endothelial cells under inflammatory conditions (TNFα), and loss of Eng influences ECFC-related permeability through the LIMK/cofilin/actin rearrangement-signaling pathway.
    • References:
      Nature. 1997 Feb 20;385(6618):729-33. (PMID: 9034190)
      Exp Cell Res. 2017 Sep 1;358(1):31-38. (PMID: 28602626)
      J Comput Chem. 2004 Oct;25(13):1605-12. (PMID: 15264254)
      Dis Model Mech. 2018 Sep 21;11(9):. (PMID: 30108051)
      PLoS One. 2012;7(2):e29948. (PMID: 22347366)
      Am J Physiol Heart Circ Physiol. 2010 Oct;299(4):H959-74. (PMID: 20656886)
      J Biol Chem. 2011 Aug 26;286(34):30034-46. (PMID: 21737454)
      FASEB J. 2004 Mar;18(3):609-11. (PMID: 14734648)
      J Thromb Haemost. 2019 Jul;17(7):1190-1194. (PMID: 31119878)
      Nucleic Acids Res. 2018 Jul 2;46(W1):W296-W303. (PMID: 29788355)
      Front Genet. 2015 Jan 07;5:457. (PMID: 25709613)
      Thromb Haemost. 2020 Sep;120(9):1313-1322. (PMID: 32688422)
      J Biol Chem. 2004 Jun 25;279(26):27440-9. (PMID: 15084601)
      Angiogenesis. 2019 May;22(2):325-339. (PMID: 30607696)
      Int J Mol Sci. 2021 Apr 01;22(7):. (PMID: 33916163)
      J Cell Mol Med. 2005 Jul-Sep;9(3):692-7. (PMID: 16202216)
      Blood. 2012 Jun 21;119(25):6162-71. (PMID: 22566602)
      Inflamm Res. 2002 Sep;51(9):464-70. (PMID: 12365720)
      Blood. 2013 Jan 10;121(2):403-15. (PMID: 23074273)
      Biomolecules. 2020 Feb 12;10(2):. (PMID: 32059544)
      Cardiovasc Res. 2005 Nov 1;68(2):235-48. (PMID: 15993872)
      Cell Rep. 2017 May 30;19(9):1917-1928. (PMID: 28564608)
      Blood Rev. 2010 Nov;24(6):203-19. (PMID: 20870325)
      Nucleic Acids Res. 2009 Jul;37(Web Server issue):W498-503. (PMID: 19433514)
      Bioinformatics. 2013 Apr 1;29(7):845-54. (PMID: 23407358)
      Cell Med. 2011 Dec 09;2(3):85-96. (PMID: 27004134)
      Cell Mol Life Sci. 2016 Apr;73(8):1715-39. (PMID: 26646071)
      J Biol Chem. 2012 Feb 24;287(9):6582-91. (PMID: 22235125)
      Invest Ophthalmol Vis Sci. 2014 Aug 26;55(10):6490-8. (PMID: 25159209)
      Thromb Haemost. 2017 Oct 5;117(10):1908-1918. (PMID: 28771278)
      Ocul Immunol Inflamm. 2021 Apr 1;:1-8. (PMID: 33793358)
      Cell Mol Life Sci. 2018 Apr;75(7):1269-1284. (PMID: 29080903)
      Biophys J. 2007 Jun 15;92(12):4254-61. (PMID: 17384060)
      J Biol Chem. 2004 Jul 30;279(31):32858-68. (PMID: 15148318)
      Methods Enzymol. 2003;374:461-91. (PMID: 14696385)
      Blood. 2016 Aug 25;128(8):1129-38. (PMID: 27301859)
      J Phys Chem B. 2013 Apr 4;117(13):3516-30. (PMID: 23406326)
      Invest Ophthalmol Vis Sci. 2018 Dec 3;59(15):6075-6088. (PMID: 30592496)
      JCI Insight. 2016 Oct 06;1(16):e88643. (PMID: 27734030)
      Phys Rev Lett. 2003 Feb 21;90(7):075503. (PMID: 12633242)
      J Clin Med. 2020 Nov 05;9(11):. (PMID: 33167572)
      Circ Res. 2010 Apr 30;106(8):1425-33. (PMID: 20224041)
      Stem Cell Rev Rep. 2020 Apr;16(2):357-368. (PMID: 31898801)
      Cell Signal. 2013 Feb;25(2):457-69. (PMID: 23153585)
      J Microsc. 2006 Dec;224(Pt 3):213-32. (PMID: 17210054)
      PLoS One. 2015 Apr 24;10(4):e0122892. (PMID: 25909848)
      Front Med (Lausanne). 2019 Jan 30;6:10. (PMID: 30761306)
      Proc Natl Acad Sci U S A. 2007 Oct 9;104(41):16281-6. (PMID: 17911245)
      FASEB J. 2015 Sep;29(9):3678-88. (PMID: 25972355)
      Am J Pathol. 2020 Mar;190(3):535-542. (PMID: 31866349)
      Exp Ther Med. 2017 Sep;14(3):1866-1870. (PMID: 28962095)
      J Biol Chem. 2002 Aug 9;277(32):29197-209. (PMID: 12015308)
      Expert Opin Ther Targets. 2017 Oct;21(10):933-947. (PMID: 28796572)
    • Contributed Indexing:
      Keywords: ECFC; HHT1; TNFα; cofilin; endoglin
    • الرقم المعرف:
      0 (Actin Depolymerizing Factors)
      0 (Endoglin)
      EC 2.7.11.1 (LIMK1 protein, human)
      EC 2.7.11.1 (Lim Kinases)
    • الموضوع:
      Date Created: 20210827 Date Completed: 20210913 Latest Revision: 20210913
    • الموضوع:
      20231215
    • الرقم المعرف:
      PMC8396367
    • الرقم المعرف:
      10.3390/ijms22168837
    • الرقم المعرف:
      34445542