Topical application of laminin-332 to diabetic mouse wounds

J Dermatol Sci. 2007 Dec;48(3):177-88. doi: 10.1016/j.jdermsci.2007.07.002. Epub 2007 Aug 24.

Abstract

Background: Keratinocyte migration is essential for wound healing and diabetic wound keratinocytes migrate poorly. Keratinocyte migration and anchorage appears to be mediated by laminin-332 (LM-332). Impaired diabetic wound healing may be due to defective LM-332 mediated keratinocyte migration.

Objective: To evaluate LM-332 expression in diabetic (db/db) and control (db/-) mice and to test LM-332 wound healing effects when applied to mouse wounds.

Methods: LM-332 expression in mouse wounds was evaluated using immunohistochemistry. LM-332 wound healing effects were evaluated by directly applying soluble LM-332, a LM-332 biomaterial, or a control to mouse wounds. Percent wound closure and histology score, based on healing extent, were measured.

Results: Precursor LM-332 expression was markedly reduced in db/db when compared to db/- mice. In vitro, soluble LM-332 and LM-332 biomaterial demonstrated significant keratinocyte adhesion. In vivo, soluble LM-332 treated wounds had the highest histology score, but significant differences were not found between wound treatments (p>0.05). No differences in percentage wound closure between treatment and control wounds were found (p>0.05).

Conclusion: The db/db wounds express less precursor LM-332 when compared to db/-. However, LM-332 application did not improve db/db wound healing. LM-332 purified from keratinocytes was primarily physiologically cleaved LM-332 and may not regulate keratinocyte migration. Application of precursor LM-332 rather than cleaved LM-332 may be necessary to improve wound healing, but this isoform is not currently available in quantities sufficient for testing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Topical
  • Animals
  • Basement Membrane / metabolism
  • Basement Membrane / pathology
  • Cell Adhesion Molecules / administration & dosage
  • Cell Adhesion Molecules / metabolism
  • Cell Adhesion Molecules / therapeutic use*
  • Cell Movement / drug effects
  • Cell Movement / physiology
  • Collagen / metabolism
  • Diabetes Complications / drug therapy*
  • Diabetes Complications / metabolism
  • Diabetes Complications / pathology
  • Integrins / metabolism
  • Keratinocytes / metabolism
  • Keratinocytes / pathology
  • Keratinocytes / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Mice, Mutant Strains
  • Wound Healing / drug effects
  • Wounds and Injuries / drug therapy*
  • Wounds and Injuries / metabolism
  • Wounds and Injuries / pathology

Substances

  • Cell Adhesion Molecules
  • Integrins
  • kalinin
  • Collagen