Lumican Accelerates Wound Healing by Enhancing α2β1 Integrin-Mediated Fibroblast Contractility

PLoS One. 2013 Jun 26;8(6):e67124. doi: 10.1371/journal.pone.0067124. Print 2013.

Abstract

Lumican is a dermatan sulfate proteoglycan highly expressed in connective tissue and has the ability to regulate collagen fibril assembly. Previous studies have shown that lumican is involved in wound healing, but the precise effects of lumican on reepithelialization and wound contraction, the two pivotal aspects of skin wound healing, have not been investigated. Here we explored the roles of lumican in fibroblast contractility, a main aspect of skin wound healing, by adopting mice skin wound healing model and the corresponding in vitro cellular experiments. Our results showed that lumican can promote skin wound healing by facilitating wound fibroblast activation and contraction but not by promoting keratinocyte proliferation and migration. Silencing of integrin α2 completely abolished the pro-contractility of lumican, indicating lumican enhances fibroblast contractility via integrin α2. Our study for the first time demonstrated that lumican can affect fibroblast's mechanical property, which is pivotal for many important pathological processes, such as wound healing, fibrosis, and tumor development, suggesting that lumican might have a potential to be used to modulate these processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Fibroblasts / cytology*
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Gene Silencing
  • HEK293 Cells
  • Humans
  • Integrin alpha2beta1 / deficiency
  • Integrin alpha2beta1 / genetics
  • Integrin alpha2beta1 / metabolism*
  • Lumican / pharmacology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Recombinant Proteins / pharmacology
  • Skin / cytology
  • Wound Healing / drug effects*

Substances

  • Integrin alpha2beta1
  • Lumican
  • Recombinant Proteins

Grants and funding

The work was supported by the National Key Sci-Tech Special Projects of Infectious Diseases (2013ZX10002-007-006), the National Science Foundation of China (81000837, 81071738, 81101600 and 81201624) and the Innovation Program of Shanghai Municipal Education Commission (12YZ043). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.