Topical application of laminin-332 to diabetic mouse wounds.
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).


CONCLUSIONS
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.
Sullivan
Stephen R
SR
Department of Surgery (Plastic and Reconstructive Surgery), University of Washington, Seattle, WA 98195-6524, United States.
Underwood
Robert A
RA
Sigle
Randall O
RO
Fukano
Yuko
Y
Muffley
Lara A
LA
Usui
Marcia L
ML
Gibran
Nicole S
NS
Antezana
Marcos A
MA
Carter
William G
WG
Olerud
John E
JE
D000287:Administration, Topical; D000818:Animals; D001485:Basement Membrane / Q000378:metabolism / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D003094:Collagen / Q000378:metabolism; D048909:Diabetes Complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016023:Integrins / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008817:Mice, Mutant Strains; D014945:Wound Healing / Q000187:drug effects; D014947:Wounds and Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000097794:Kalinin
D015815:Cell Adhesion Molecules; D003094:Collagen; D016023:Integrins; D000097794:Kalinin
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