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Research Article| Volume 240, ISSUE 2, P453-461, June 2015

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Effects of estrogen on growth and smooth muscle differentiation of vascular wall-resident CD34+ stem/progenitor cells

  • Author Footnotes
    1 Co-first authors with equal contribution.
    Yan Wu
    Footnotes
    1 Co-first authors with equal contribution.
    Affiliations
    Department of Anatomy and Embryology, Wuhan University School of Basic Medical Sciences, 135 Donghu Road, Wuhan 430071, Hubei, PR China
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  • Author Footnotes
    1 Co-first authors with equal contribution.
    Yan Shen
    Footnotes
    1 Co-first authors with equal contribution.
    Affiliations
    Department of Physiology, Wuhan University School of Basic Medical Sciences, 135 Donghu Road, Wuhan 430071, Hubei, PR China
    Search for articles by this author
  • Kai Kang
    Affiliations
    Department of Anatomy and Embryology, Wuhan University School of Basic Medical Sciences, 135 Donghu Road, Wuhan 430071, Hubei, PR China
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  • Yanhong Zhang
    Affiliations
    Department of Anatomy and Embryology, Wuhan University School of Basic Medical Sciences, 135 Donghu Road, Wuhan 430071, Hubei, PR China
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  • Feng Ao
    Affiliations
    Department of Anatomy and Embryology, Wuhan University School of Basic Medical Sciences, 135 Donghu Road, Wuhan 430071, Hubei, PR China
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  • Yu Wan
    Correspondence
    Corresponding authors.
    Affiliations
    Department of Physiology, Wuhan University School of Basic Medical Sciences, 135 Donghu Road, Wuhan 430071, Hubei, PR China
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  • Jian Song
    Correspondence
    Corresponding authors.
    Affiliations
    Department of Anatomy and Embryology, Wuhan University School of Basic Medical Sciences, 135 Donghu Road, Wuhan 430071, Hubei, PR China
    Search for articles by this author
  • Author Footnotes
    1 Co-first authors with equal contribution.

      Highlights

      • Effect of estrogen replacing therapy (ERT) on cardiovascular events is controversial.
      • Investigate estrogen’s effects on vascular-resident stem/progenitor cells (VRS/Pc).
      • Estrogen can promote VRS/Pc proliferation and differentiation.
      • Thus, it functions to maintain homeostasis of vascular wall.
      • Older women does not benefit from ERT probably due to a shrink of VRS/Pc reservoir.

      Abstract

      Objectives: To investigate the effects of estrogen on growth and smooth muscle cell (SMC)-differentiation of vascular wall-resident CD34+ stem/progenitor cells (VRS/Pcs). Methods and Results: The existence of CD34+ VRS/Pcs was confirmed by immunohistochemistry in the adventitia of arteries of young (2-month-old) and old (24-month-old) female SD rats with less CD34+ adventitial cells detected in the old. The VRS/Pcs isolated from young animals were grown in Stem cell growth medium or induced to differentiate into SMC with PDGF-BB in the presence or absence of 17β-estrodiol (E2). Flow cytometry, RT-qPCR and Western blot showed that E2 promoted Brdu incorporation of the CD34+ VRS/Pcs growing in Stem cell growth medium; but when the cells were incubated in PDGF-BB, the hormone enhanced their expression of SMC marker SM22. ChIP and IP assays showed that E2 significantly promoted the binding of pELK1-SRF complex to the promoter of c-fos gene in CD34+ VRS/Pcs growing in the Stem cell growth medium; but when the cells were stimulated with PDGF-BB, an E2-enhanced binding of myocardin-SRF to the promoter of SM22 gene was found with enhanced expression of SRC3 and its binding to myocardin. The effects of E2 above could be blocked by the estrogen receptor antagonist ICI 182,780 or inhibited by SRF-siRNA. Conclusion: Estrogen has dual effects on CD34+ VRS/Pcs. For the undifferentiated VRS/Pcs, it accelerates their proliferation by enhancing binding of pELK1-SRF complex to c-fos gene; while for the differentiating VRS/Pcs, it promotes their differentiation to SMC through a mechanism of SRC3-mediated interaction of myocardin-SRF complex with SM22 gene.

      Keywords

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