title: 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.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Research Institute of Medical Science, Konkuk University School of Medicine, Chungju, 380-704, Korea.
authors.forename: Soon Heum
authors.initials: SH
authors.lastname: Kim
authors.forename: Seung-Hyo
authors.initials: SH
authors.lastname: Jung
authors.forename: Hong
authors.initials: H
authors.lastname: Chung
authors.forename: Dong In
authors.initials: DI
authors.lastname: Jo
authors.forename: Cheol Keun
authors.initials: CK
authors.lastname: Kim
authors.forename: Seung Hwa
authors.initials: SH
authors.lastname: Park
authors.forename: Kyung-Jong
authors.initials: KJ
authors.lastname: Won
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Jeon
authors.forename: Bokyung
authors.initials: B
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017306:Annexin A2 / Q000096:biosynthesis*; D001052:Apoferritins / Q000096:biosynthesis; D002265:Carboxylic Ester Hydrolases / Q000096:biosynthesis; D049109:Cell Proliferation; D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis; D024061:Collagen Type III / Q000096:biosynthesis; D024062:Collagen Type V / Q000096:biosynthesis; D015536:Down-Regulation; D005260:Female; D005347:Fibroblasts; D020869:Gene Expression Profiling; D006801:Humans; D007627:Keloid / Q000378:metabolism*; D008297:Male; D008840:Microfilament Proteins / Q000096:biosynthesis; D008875:Middle Aged; D034622:RNA Interference; D034741:RNA, Small Interfering; D012709:Serum Albumin / Q000096:biosynthesis; D012867:Skin / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053802:Tryptases / Q000096:biosynthesis; D015854:Up-Regulation; D055815:Young Adult
chemical_list: C472822:ANXA2 protein, human; D017306:Annexin A2; D024042:Collagen Type I; D024061:Collagen Type III; D024062:Collagen Type V; D008840:Microfilament Proteins; D034741:RNA, Small Interfering; D012709:Serum Albumin; D001052:Apoferritins; D002265:Carboxylic Ester Hydrolases; C022363:6-phosphogluconolactonase; D053802:Tryptases