Gene expression in human keloids is altered from dermal to chondrocytic and osteogenic lineage.
Keloids are a dermal fibrotic disease whose etiology remains totally unknown and for which there is no successful treatment. Here, we employed cDNA microarray analysis to examine gene expression in keloid lesions and control skin. We found that 32 genes among the 9000 tested were strongly up-regulated in keloid lesions, of which 21 were confirmed by Northern blotting. These included at least seven chondrocyte/osteoblast marker genes, and RT-PCR analysis revealed that transcription factors specific for these genes, SOX9 and CBFA1, were induced. Immunostaining and in situ hybridization further supported that these markers are expressed in keloid lesions. Intriguingly, scleraxis, a transcription factor known as a marker of tendons and ligaments, was also induced in keloid fibroblasts. We propose that reprogramming of gene expression or disordered differentiation from a dermal pattern to that of a chondrocytic/osteogenic lineage, probably closer to that of tendon/ligament lineage, may be involved in the etiology of keloids.
Naitoh
Motoko
M
Department of Molecular and Cellular Biology, Institute for Frontier Medical Science, Kyoto University, Kyoto 606-8397, Japan.
Kubota
Hiroshi
H
Ikeda
Mika
M
Tanaka
Toshinori
T
Shirane
Hirofumi
H
Suzuki
Shigehiko
S
Nagata
Kazuhiro
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D002356:Cartilage; D019070:Cell Lineage / Q000502:physiology*; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D024161:Collagen Type XI / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006609:High Mobility Group Proteins / Q000235:genetics; D006801:Humans; D007627:Keloid / Q000235:genetics*; D008875:Middle Aged; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055758:SOX9 Transcription Factor; D012867:Skin / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; D024161:Collagen Type XI; D050659:Core Binding Factor Alpha 1 Subunit; D016326:Extracellular Matrix Proteins; D006609:High Mobility Group Proteins; D012333:RNA, Messenger; D055758:SOX9 Transcription Factor; D014157:Transcription Factors; C093504:SCX protein, human; C527932:SOX9 protein, human