Altered expression of L-arginine metabolism pathway genes in chronic wounds in recessive dystrophic epidermolysis bullosa.
Individuals with the severe, mutilating Hallopeau-Siemens form of recessive dystrophic epidermolysis bullosa (HS-RDEB) have trauma-induced blisters and skin erosions which often progress to wounds that are slow to heal. These chronic wounds cause considerable morbidity and there is an increased risk of squamous cell carcinoma arising in the wound margins. Currently, little is known about the keratinocyte cell biology in these wounds. Therefore, we compared the gene expression profiles of wound edge with nonwounded skin from two individuals with HS-RDEB. Trauma-induced wound sites had been present in both patients for more than 3 months. Hybridizations using DermArray gene expression filters showed relative differences in gene expression between wounded and unwounded skin. Notably, there was a fivefold increase in expression of arginase-1 (ARG1) in the chronic wound samples. Expression of seven other genes relevant to L-arginine metabolism also showed differences greater than twofold. L-arginine is known to have a critical role in the synthesis of nitric oxide as part of normal tissue repair. Although alterations in arginase isoenzymes have been detected previously in other chronic wounds (human and animal models), this is the first study to demonstrate differences in several components of the L-arginine metabolism pathway in chronic wounds, and the first to examine chronic wounds in HS-RDEB. The data show that the cascade of L-arginine metabolites is altered in HS-RDEB and the findings may provide new insight into the pathology of chronic wounds in this genodermatosis.
Wessagowit
V
V
Genetic Skin Disease Group, St John's Institute of Dermatology, The Guy's, King's College and St Thomas' Hospitals' Medical School, London, UK.
Mallipeddi
R
R
McGrath
J A
JA
South
A P
AP
D000328:Adult; D001119:Arginase / Q000235:genetics / Q000378:metabolism; D001120:Arginine / Q000378:metabolism*; D002908:Chronic Disease; D016108:Epidermolysis Bullosa Dystrophica / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D012867:Skin / Q000293:injuries* / Q000378:metabolism; D014945:Wound Healing
D001120:Arginine; D001119:Arginase