Proteomic Approach to Skin Regeneration in a Marine Teleost: Modulation by Oestradiol-17β

Skin and scale formation and regeneration in teleosts have mainly been described from a morphological perspective, and few studies of the underlying molecular events exist. The present study evaluates (1) the change in the skin proteome during its regeneration in a marine teleost fish (gilthead sea bream, Sparus aurata) and (2) the impact of oestradiol-17 beta (I center dot(2)) on regeneration and the involvement of oestrogen receptor (ER) isoforms. Thirty-five candidate proteins were differentially expressed (p < 0.05) between intact and regenerated skin proteome 5 days after scale removal, and 27 proteins were differentially expressed after E-2 treatment. Agglomerative hierarchical clustering of the skin proteome revealed that the skin treated with E-2 clustered most closely to intact skin, while regenerating untreated skin formed an independent cluster. Gene Ontology classification associated the differentially expressed proteins in E-2-treated skin with developmental processes and cellular morphogenesis. The proteins modified during skin regeneration suggest a balance exists between immune response and anatomical repair. Overall, the results indicate that, even after 5 days regeneration, the composition of mature skin is not attained, and endocrine factors, in particular E-2, can accelerate wound repair acting possibly via ER beta s expressed in the skin-scales. Several candidate proteins probably involved in scale development, osteoglycin, lipocalin2 and lamin A and the transcription factors PHD and grainyhead were identified. Future studies of fish skin regeneration will be required to provide further insight into this multistage process, and the present study indicates it will be useful to explore immune adaptations of epithelia permanently exposed to an aqueous environment.