Hyperglycaemic conditions hamper keratinocyte locomotion via sequential inhibition of distinct pathways: new insights on poor wound closure in patients with diabetes.
Br J Dermatol
; 160(6): 1206-14, 2009 Jun.
Article
em En
| MEDLINE
| ID: mdl-19298270
ABSTRACT
BACKGROUND:
Diabetes mellitus (DM) is characterized by impaired insulin signalling, elevated plasma glucose, and predisposition towards complications involving several organs. A major complication of DM is impairment of wound healing. In the re-epithelialization process during wound healing, migration of keratinocytes is a crucial step. Our previous report demonstrated that keratinocytes cultured in hyperglycaemic media showed decreased cell mobility.OBJECTIVES:
The current study aimed to explore the effects of high glucose on keratinocyte migration after different treatment durations.METHODS:
Keratinocytes were cultivated for indicated time periods under various concentrations of glucose. Relevant assays including Transwell migration and in vitro wound scratch assays, flow cytometric analysis, matrix metalloproteinase-1 (MMP-1) activity assay, determination of mRNA expression and Western blotting were performed.RESULTS:
We demonstrated that (i) keratinocyte motility progressively and significantly decreased; (ii) the keratinocyte activation marker K16 was significantly suppressed; (iii) expression of alpha2beta1 integrin and MMP-1, both crucial for keratinocyte locomotion on collagen type I, was significantly downregulated; and (iv) expression of the phosphorylated signal transducer and activator of transcription-1 significantly decreased after hyperglycaemic treatment. More specifically, different pathways become involved after prolonged duration of high glucose cultivation to reduce keratinocyte locomotion further.CONCLUSIONS:
We have demonstrated that high glucose treatment results in progressive suppression of keratinocyte locomotion and elucidated the molecular mechanisms involved. These results provide a reasonable explanation for the poor wound healing seen in patients with DM.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Cicatrização
/
Queratinócitos
/
Movimento Celular
/
Diabetes Mellitus
/
Glucose
Limite:
Humans
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article