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Role of TGF-β co-receptor CD109 in extracellular matrix production of smooth muscle cells

Li, Y. (CNRS U8256 INSERM U1164 UMPC, Paris, France ) ; Louis, H. (INSERM U1116, université ) ; Gao-Li, J. (de Lorraine, Nancy, France ) ; Parlakian, A. (CNRS U8256 INSERM U1164 UMPC, Paris, France ) ; Agbulut, O. (CNRS U8256 INSERM U1164 UMPC, Paris, France ) ; Lacolley, P. (CNRS U8256 INSERM U1164 UMPC, Paris, France ) ; Regnault, V. (INSERM U1116, université ) ; Li, Z. (de Lorraine, Nancy, France ) ;
  • 초록  

    CD109 is a glycosylphosphatidylinositol (GPI)-linked glycoprotein located on the plasma membrane and has no intracellular domain. It has been reported that it attenuates the TGF-β signaling in skin fibroblastes and cancer cells by competitive binding to TGF-β factors and promoting internalization and degradation of TGF-β receptors. We found less production of extracellular matrix (ECM) and higher expression of CD109 in the carotids of angiotensin II-treated mice in which integrin alphaV is inactivated specifically in smooth muscle cells (SMC). We want to study the role of CD109 on the production of extracellular matrix proteins in primary SMC. CD109 is overexpressed by expressing vector (in collaboration with Dr. Murakumo Y.) or decreased by CD109 siRNA in SMC that is analyzed by the cellular and molecular methods. Our results showed that the overexpression of full-length form or soluble form of CD109 attenuated the production of ECM proteins such as collagens and fibronectin in SMC, in contrast with the situation in which the CD109 is knock-downed by siRNA. The response to TGF-β1 and angiotensin II treatment is also attenuated in CD109 overexpression SMC and enhanced in CD109 knock-down SMC. The signaling pathways (phosphorylation of ERK, Akt, Smad2/3, STAT3) related to CD109 are under the investigation. The promoter of CD109 is also under the study in order to understand the mechanism leading to upregulation of CD109 in response to angiotensin II treatment in the integrin aphaV SMC-KO mice. CD109 receptor could be one important regulator of vascular fibrosis and potential target for anti-fibrosis treatment.


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