Regulation of Epithelial Differentiation and Proliferation by the Stroma: A Role for the Retinoblastoma Protein.

Adam Pickard, Ann-Christin Cichon, Craig Menges, Daksha Patel, Dennis McCance

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Signaling between the epithelium and stromal cells is crucial for growth, differentiation, and repair of the epithelium. Although the retinoblastoma protein (Rb) is known to regulate the growth of keratinocytes in a cell-autonomous manner, here we describe a function of Rb in the stromal compartment. We find that Rb depletion in fibroblasts leads to inhibition of differentiation and enhanced proliferation of the epithelium. Analysis of conditioned medium identified that keratinocyte growth factor (KGF) levels were elevated following Rb depletion. These findings were also observed with organotypic co-cultures. Treatment of keratinocytes with KGF inhibited differentiation and enhanced keratinocyte proliferation, whereas reduction of KGF levels in Rb-depleted fibroblasts was able to restore expression of differentiation markers. Our findings suggest a crucial role for dermal fibroblasts in regulating the differentiation and proliferation of keratinocytes, and we demonstrate a role for stromal Rb in this cross-talk.Journal of Investigative Dermatology advance online publication, 14 June 2012;doi:10.1038/jid.2012.201.
Original languageEnglish
Pages (from-to)2691–2699
JournalJournal of investigative dermatology
Volume132
Issue numbernull
Early online date14 Jun 2012
DOIs
Publication statusPublished - 14 Jun 2012

ASJC Scopus subject areas

  • Dermatology
  • Molecular Biology
  • Cell Biology
  • Biochemistry

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