title: Identification and characterization of cartilage oligomeric matrix protein as a novel pathogenic factor in keloids.
abstract: To elucidate pathogenic molecules in keloids, microarray analysis was performed using RNAs extracted from keloid-derived fibroblasts and normal skin-derived fibroblasts from the same patient with a typical keloid. Among 11 up-regulated extracellular matrix genes, cartilage oligomeric matrix protein (COMP) was most prominently increased. Up-regulation of COMP mRNA and protein was confirmed in the keloid tissue by quantitative RT-PCR and Western blot. Using immunohistochemistry, we compared 15 keloids and 6 control normal tissues using a COMP-specific antibody and found that COMP stained positively in 10 keloids (66.7%), whereas no staining was observed in normal tissues, demonstrating the ectopic expression of COMP in keloids. Comparing keloids smaller or larger than 10 cm(2), the larger keloids were significantly more intensely stained with the COMP-specific antibody. Because COMP reportedly accelerates collagen type I fibril assembly, we examined whether extracellular type I collagen deposition is altered by silencing COMP mRNA by small interfering RNA (siRNA). Immunocytochemistry showed at 96 hours after transfection with COMP siRNA that the extracellular deposition of type I collagen was decreased compared to that observed with control siRNA. Further, COMP knockdown decreased amount collagens type I to V in the medium and on the cell surfaces. Our data suggest that COMP facilitates keloid formation by accelerating collagen deposition, thus providing a new therapeutic target.
authors.affiliation: Department of Regenerative Dermatology, Graduate School of Medicine, Osaka University, Osaka, Japan. inui@r-derma.med.osaka-u.ac.jp
authors.forename: Shigeki
authors.initials: S
authors.lastname: Inui
authors.forename: Fumie
authors.initials: F
authors.lastname: Shono
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakajima
authors.forename: Ko
authors.initials: K
authors.lastname: Hosokawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Itami
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D064236:Cartilage Oligomeric Matrix Protein; D002648:Child; D002675:Child, Preschool; D024042:Collagen Type I / Q000378:metabolism; D020405:Dermis / Q000187:drug effects / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007627:Keloid / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D064235:Matrilin Proteins; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D034741:RNA, Small Interfering / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D055815:Young Adult
chemical_list: D064236:Cartilage Oligomeric Matrix Protein; D024042:Collagen Type I; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D064235:Matrilin Proteins; D034741:RNA, Small Interfering; C577553:TSP5 protein, human; D053773:Transforming Growth Factor beta1