Keratinocyte migration, proliferation, and differentiation in chronic ulcers from patients with diabetes and normal wounds.
Epithelialization of normal acute wounds occurs by an orderly series of events whereby keratinocytes migrate, proliferate, and differentiate to restore barrier function. The keratinocytes in the epidermis of chronic ulcers fail to execute this series of events. To better understand the epithelial dynamics of chronic ulcers, we used immunohistochemistry to evaluate proliferation, differentiation, adhesion, and migration in keratinocytes along the margin of chronic ulcers from patients with diabetes mellitus. We compared these features with keratinocytes from the migrating epithelial tongues of acute incisional and excisional wounds from normal volunteers. Keratinocytes at the chronic ulcer edge are highly proliferative (Ki67 proliferation marker), have an activated phenotype (K16), do not stain for keratins involved in epidermal differentiation (K10 and K2), and show a reduced expression of LM-3A32 (uncleaved, precursor of the alpha3 chain of laminin 5), a key molecule present on migrating epithelium. In contrast, keratinocytes in normal acute wound migrating epithelium do not express the proliferation marker Ki67 but do express K10, K2, and LM-3A32. A better understanding of molecular mechanisms involved in keratinocyte migration may lead to molecular targets for therapies for impaired wound healing.
Usui
Marcia L
ML
Department of Medicine (Dermatology), University of Washington, 1959 NE Pacific Street, Box 356524, Seattle, WA 98195-6524, USA. usui@u.washington.edu
Mansbridge
Jonathan N
JN
Carter
William G
WG
Fujita
Mayumi
M
Olerud
John E
JE
D000368:Aged; D001132:Arm; D002448:Cell Adhesion; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002908:Chronic Disease; D017719:Diabetic Foot / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D015603:Keratinocytes / Q000473:pathology* / Q000502:physiology*; D007866:Leg; D008297:Male; D012867:Skin / Q000293:injuries* / Q000473:pathology*; D014945:Wound Healing