Deregulation of keratinocyte differentiation and activation: A hallmark of venous ulcers

Olivera Stojadinovic, Irena Pastar, Sasa Vukelic, Mỹ G. Mahoney, Donna Brennan, Agata Krzyzanowska, Michael Golinko, Harold Brem, Marjana Tomic-Canic

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

Epidermal morphology of chronic wounds differs from that of normal epidermis. Biopsies of non-healing edges obtained from patients with venous ulcers show thick and hyperproliferative epidermis with mitosis present in suprabasal layers. This epidermis is also hyper-keratotic and parakeratotic. This suggests incomplete activation and differentiation of keratinocytes. To identify molecular changes that lead to pathogenic alterations in keratinocyte activation and differentiation pathways we isolated mRNA from non-healing edges deriving from venous ulcers patients and determined transcriptional profiles using Affymetrix chips. Obtained transcriptional profiles were compared to those from healthy, unwounded skin. As previously indicated by histology, we found deregulation of differentiation and activation markers. We also found differential regulation of signalling molecules that regulate these two processes. Early differentiation markers, keratins K1/K10 and a subset of small proline-rich proteins, along with the late differentiation marker filaggrin were suppressed, whereas late differentiation markers involucrin, transgultaminase 1 and another subset of small proline-rich proteins were induced in ulcers when compared to healthy skin. Surprisingly, desomosomal and tight junction components were also deregulated. Keratinocyte activation markers keratins K6/K16/K17 were induced. We conclude that keratinocytes at the non-healing edges of venous ulcers do not execute either activation or differentiation pathway, resulting in thick callus-like formation at the edge of a venous ulcers.

Original languageEnglish (US)
Pages (from-to)2675-2690
Number of pages16
JournalJournal of Cellular and Molecular Medicine
Volume12
Issue number6B
DOIs
StatePublished - Dec 1 2008

Keywords

  • Chronic wounds
  • Desmosomes
  • Keratinocyte activation
  • Keratinocyte differentiation
  • Microarrays
  • Transcriptional profiling
  • Venous ulcers
  • Wound healing

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine

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