Kruppel-like factor KLF4 facilitates cutaneous wound healing by promoting fibrocyte generation from myeloid-derived suppressor cells

Lingling Ou, Ying Shi, Wenqi Dong, Chunming Liu, Thomas J. Schmidt, Prakash Nagarkatti, Mitzi Nagarkatti, Daping Fan, Walden Ai

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Pressure ulcers (PUs) are serious skin injuries whereby the wound healing process is frequently stalled in the inflammatory phase. Myeloid-derived suppressor cells (MDSCs) accumulate as a result of inflammation and promote cutaneous wound healing by mechanisms that are not fully understood. Recently, MDSCs have been shown to differentiate into fibrocytes, which serve as emerging effector cells that enhance cell proliferation in wound healing. We postulate that in wound healing MDSCs not only execute their immunosuppressive function to regulate inflammation but also stimulate cell proliferation once they differentiate into fibrocytes. In the current study, by using full-thickness and PU mouse models, we found that Kruppel-like factor 4 (KLF4) deficiency resulted in decreased accumulation of MDSCs and fibrocytes, and wound healing was significantly delayed. Conversely, KLF4 activation by the plant-derived product Mexicanin I increased the number of MDSCs and fibrocytes and accelerated the wound healing. Collectively, our study revealed a previously unreported function of MDSCs in cutaneous wound healing and identified Mexicanin I as a potential agent to accelerate PU wound healing.

Original languageEnglish
Pages (from-to)1425-1434
Number of pages10
JournalJournal of Investigative Dermatology
Volume135
Issue number5
DOIs
StatePublished - May 22 2015

Bibliographical note

Funding Information:
This work was supported by NIH grant (R03AR060987) and ASPIRE-I from University of South Carolina to WA. We thank Dr Udai P. Singh and Mr Kyle McCloskey for technical assistance and Dr Joseph S. Janicki for his editing of the manuscript.

Publisher Copyright:
© 2015 The Society for Investigative Dermatology.

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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