Expression of HSP70 in healing wounds of diabetic and nondiabetic mice.
BACKGROUND
Heat shock proteins (HSPs) stabilize intracellular processes of cells under stress. Little is known about the role of HSPs in wound healing, or whether their expression is altered by systemic disease. The focus of this study was to examine the local heat shock response to wounding in diabetic mice.


METHODS
Congenitally diabetic and phenotypically normal mice underwent standardized full-thickness cutaneous wounding. Mice were sacrificed at sequential time points and the wound beds excised. Tissues underwent immunohistochemical (IHC) and RT-PCR analyses for inducible HSP70.


RESULTS
HSP70 protein expression in the wound bed by IHC peaked at 24 h in the nondiabetic mice. Expression of HSP70 was delayed in the diabetic mice until Day 3, which correlates with the clinical delay in healing seen in this model. The protein was especially prominent in the epithelium and in inflammatory cells migrating into the granulation tissue matrix. RT-PCR demonstrated upregulation of HSP70 mRNA within 12 h after wounding, lasting until Day 3, and decreasing thereafter in both the nondiabetic and the diabetic animals.


CONCLUSIONS
Cutaneous wounding produces a HSP response in inflammatory cells, and expression of inducible HSP70 is delayed in diabetic mice. This delay may be related to the impaired inflammatory response of diabetics, and may contribute to impaired wound healing. The wound may be a continuing source of the heat shock response in inflammatory cells after injury.
McMurtry
A L
AL
Department of Surgery, University of California, Davis, Davis, California 95616, USA.
Cho
K
K
Young
L J
LJ
Nelson
C F
CF
Greenhalgh
D G
DG
D000818:Animals; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics; D012333:RNA, Messenger; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000293:injuries / Q000473:pathology; D013997:Time Factors; D014018:Tissue Distribution; D014945:Wound Healing / Q000502:physiology*; D014950:Wounds, Penetrating / Q000473:pathology / Q000503:physiopathology
D018840:HSP70 Heat-Shock Proteins; D012333:RNA, Messenger