Angiotensin-II mediates nonmuscle myosin II activation and expression and contributes to human keloid disease progression.

Published

Journal 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.

Full Text

Duke Authors

Cited Authors

  • Bond, JE; Bergeron, A; Thurlow, P; Selim, MA; Bowers, EV; Kuang, A; Levinson, H

Published Date

  • January 2011

Published In

Volume / Issue

  • 17 / 11-12

Start / End Page

  • 1196 - 1203

PubMed ID

  • 21792479

Pubmed Central ID

  • 21792479

Electronic International Standard Serial Number (EISSN)

  • 1528-3658

International Standard Serial Number (ISSN)

  • 1076-1551

Digital Object Identifier (DOI)

  • 10.2119/molmed.2010.00265

Language

  • eng