Abnormal
scarring results from the expression and composition of extracellular matrix molecules. The transcription and translation of
collagens I and III,
fibronectin,
laminin,
periostin, and
tenascin are all increased in raised dermal
scar tissue. However, human
keloid development is not fully defined. In this study, we identified
proteins expressed differentially between normal skin and
keloid scar tissues and examined their function in
keloid formation using fibroblasts. Skin specimens from normal volunteers and patients with
keloids were obtained by skin biopsy. Whole
proteins were isolated by two-dimensional electrophoresis, and differentially expressed
proteins were identified by matrix-assisted
laser desorption/ionization-time of flight/time of flight mass spectrometry.
Protein function was determined by proliferation assay using
annexin A2-overexpressing
keloid fibroblasts. The expression of 11
protein spots was altered by at least 1.5-fold in patients with
keloids than in normal volunteers. Of these
proteins,
annexin A2, a
pre-serum amyloid P component,
serum albumin precursor, and
tryptase-I, were down-regulated in
keloid tissue compared to normal skin.
Collagen alpha 1(V) chain precursor,
collagen alpha 1(I) chain precursor,
ferritin light subunit, alpha 1(III)
collagen,
6-phosphogluconolactonase, and
calponin 2 were up-regulated. Diminished expression of
annexin A2 was confirmed by immunoblotting and immunohistochemistry. Treatment with the recombinant human
epidermal growth factor increased proliferation of
keloid fibroblasts, which was more inhibited in
annexin A2-overexpressing fibroblasts than in non-transfected control cells. These results imply that
annexin A2 may participate in
keloid formation by inhibiting
keloid fibroblast proliferation. Therefore, it is concluded that
annexin A2 may be a valuable therapeutic target for
keloid lesions.