title: Increased c-Met phosphorylation is related to keloid pathogenesis: implications for the biological behaviour of keloid fibroblasts.
abstract: Keloid is induced by a pathological wound healing response, and hepatocyte growth factor (HGF) is known to be involved in tissue repair via the activation of its primary receptor, c-Met. We aimed to investigate whether c-Met activation is implicated in keloid pathogenesis. HGF, c-Met, phosphorylated c-Met (p-Met), Ki-67, collagen I protein, and MET gene expression were detected in five normal skin and 30 keloid tissues by immunohistochemistry and quantitative real-time polymerase chain reaction analysis, respectively. The influence of p-Met expression on the biological behaviour of keloid fibroblasts was further investigated with regard to cell proliferation, motility, invasiveness, collagen I expression, and intracellular signaling in vitro. p-Met protein and MET gene expression but not HGF or c-Met protein expression showed significant increases in keloid tissues than dermal layer of normal skin tissues. In keloid tissues, p-Met expression was significantly associated with keloid size, Ki-67 and collagen I expression. Moreover, p-Met expression was also related to proliferation, migration, invasiveness, collagen I expression and activation of AKT and Erk in keloid fibroblasts in vitro. c-Met activation may have a strong influence on keloid pathogenesis, and it can be investigated further as a potential molecular target for keloid therapy.
authors.affiliation: Department of Dermatology, Yanbian University Hospital, Yanji City, Jilin Province, China.
authors.forename: Zhehu
authors.initials: Z
authors.lastname: Jin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007627:Keloid / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism / Q000473:pathology; D013449:Sulfonamides / Q000494:pharmacology; D055815:Young Adult
chemical_list: C478479:((3Z)-N-(3-chlorophenyl)-3-((3,5-dimethyl-4-((4-methylpiperazin-1-yl)carbonyl)-1H-pyrrol-2-yl)methylene)-N-methyl-2-oxo-2,3-dihydro-1H-indole-5-sulfonamide); C066855:HGF protein, human; D007211:Indoles; D019394:Ki-67 Antigen; D010879:Piperazines; D013449:Sulfonamides; D017228:Hepatocyte Growth Factor; D003094:Collagen; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met