Molecular Medicine

, Volume 17, Issue 11–12, pp 1196–1203 | Cite as

Angiotensin-II Mediates Nonmuscle Myosin II Activation and Expression and Contributes to Human Keloid Disease Progression

  • Jennifer E. Bond
  • Andrew Bergeron
  • Peter Thurlow
  • M. Angelica Selim
  • Edith V. Bowers
  • Anna Kuang
  • Howard Levinson
Research Article


Aberrant fibroblast migration in response to fibrogenic peptides plays a significant role in keloid pathogenesis. Angiotensin II (Ang II) is an octapeptide hormone recently implicated as a mediator of organ fibrosis and cutaneous repair. Ang II promotes cell migration but its role in keloid fibroblast phenotypic behavior has not been studied. We investigated Ang II signaling in keloid fibroblast behavior as a potential mechanism of disease. Primary human keloid fibroblasts were stimulated to migrate in the presence of Ang II and Ang II receptor 1 (AT1), Ang II receptor 2 (AT2) or nonmuscle myosin II (NMM II) antagonists. Keloid and the surrounding normal dermis were immunostained for NMM IIA, NMM IIB, AT2 and AT1, expression. Primary human keloid fibroblasts were stimulated to migrate with Ang II and the increased migration was inhibited by the AT1, antagonist EMD66684, but not the AT2 antagonist PD123319. Inhibition of the promigratory motor protein NMM II by addition of the specific NMM II antagonist blebbistatin inhibited Ang II-stimulated migration. Ang II stimulation of NMM II protein expression was prevented by AT1 blockade but not by AT2 antagonists. Immunostaining demonstrated increased NMM IIA, NMM IIB and AT1 expression in keloid fibroblasts compared with scant staining in normal surrounding dermis. AT2 immunostaining was absent in keloid and normal human dermal fibroblasts. These results indicate that Ang II mediates keloid fibroblast migration and possibly pathogenesis through AT1, activation and upregulation of NMM II.



The project was supported by an NIH Mentored Clinical Scientist Award (K08) grant GM085562-01 (to H. Levinson), a Plastic Surgery Education Foundation Fellowship and supplemental support from the Division of Plastic and Reconstructive Surgery and Departments of Pathology and Surgery at Duke University. The authors wish to thank Trung Ho for his help with immunohistology.


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Copyright information

© The Feinstein Institute for Medical Research 2011

Authors and Affiliations

  • Jennifer E. Bond
    • 1
  • Andrew Bergeron
    • 1
  • Peter Thurlow
    • 1
  • M. Angelica Selim
    • 2
  • Edith V. Bowers
    • 2
  • Anna Kuang
    • 3
  • Howard Levinson
    • 1
    • 2
  1. 1.Division of Plastic and Reconstructive Surgery, Department of SurgeryDuke University Medical CenterDurhamUSA
  2. 2.Department of PathologyDuke University Medical CenterDurhamUSA
  3. 3.Division of Plastic and Reconstructive Surgery, Department of SurgeryOregon Health and Science UniversityPortlandUSA

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