Annexin A2 participates in human skin keloid formation by inhibiting fibroblast proliferation

Abstract

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.

Novel contribution to clubfoot pathogenesis: The possible role of extracellular matrix proteins

“…Type V collagen is particularly abundant in vascular tissues and contributes to binding to other connective tissue cells . This collagen type was detected as upregulated in human skin keloid formation . The major function of collagen VI is probably as an anchoring meshwork connecting collagen fibers to the surrounding matrix, but the precise role of collagen VI in cartilage has not been clearly defined .…”

“…23 This collagen type was detected as upregulated in human skin keloid formation. 24 The major function of collagen VI is probably as an anchoring meshwork connecting collagen fibers to the surrounding matrix, but the precise role of collagen VI in cartilage has not been clearly defined. 25 Veidal et al suggested that collagen VI turnover is a central player in liver fibrogenesis.…”

Noninvasive analysis of skin proteins in healthy Chinese subjects using an Orbitrap Fusion Tribrid mass spectrometer

“…Overexpression of extracellular matrix protein 1 could regulate angiogenesis . Studies have also found that the expression of extracellular matrix molecules is associated with scar formation, and the levels of annexin A2 and serum albumin precursors in keloids are downregulated compared to those in normal skin …”

“…47 Studies have also found that the expression of extracellular matrix molecules is associated with scar formation, and the levels of annexin A2 and serum albumin precursors in keloids are downregulated compared to those in normal skin. 48 Dermcidin was first discovered in the sweat glands of human skin and has broad-spectrum antimicrobial effects 49 ; this protein is found in the sweat glands of human skin as part of the innate immune defense system. It has been demonstrated that dermcidin concentrations in the sweat of patients infected with trichophyton are lower than those healthy subjects.…”

Non‑invasive proteome‑wide quantification of skin barrier‑related proteins using label‑free LC‑MS/MS analysis

“…In this study, the expression of annexin A2 was observed, this protein functions in regulating fibroblast proliferation and migration. It is hypothesized that Annexin A2 is involved in skin keloid formation and may be a potential target for therapeutic interventions of keloid lesions (51).…”