title: Epidermal hyperplasia and appendage abnormalities in mice lacking CD109.
abstract: CD109, a glycosylphosphatidylinositol-anchored glycoprotein, is highly expressed in several types of human cancer tissues, in particular, squamous cell carcinomas. In normal human tissues, human CD109 expression is limited to certain cell types including myoepithelial cells of the mammary, lacrimal, salivary, and bronchial glands and basal cells of the prostate and bronchial epithelium. Although CD109 has been reported to negatively regulate transforming growth factor-β signaling in keratinocytes in vitro, its physiologic role in vivo remains largely unknown. To investigate the function of CD109 in vivo, we generated CD109-deficient (CD109(-/-)) mice. Although CD109(-/-) mice were born normally, transient impairment of hair growth was observed. At histologic analysis, kinked hair shafts, ectatic hair follicles with an accumulation of sebum, and persistent hyperplasia of the epidermis and sebaceous glands were observed in CD109(-/-) mice. Immunohistochemical analysis revealed thickening of the basal and suprabasal layers in the epidermis of CD109(-/-) mice, which is where endogenous CD109 is expressed in wild-type mice. Although CD109 was reported to negatively regulate transforming growth factor-β signaling, no significant difference in levels of Smad2 phosphorylation was observed in the epidermis between wild-type and CD109(-/-) mice. Instead, Stat3 phosphorylation levels were significantly elevated in the epidermis of CD109(-/-) mice compared with wild-type mice. These results suggest that CD109 regulates differentiation of keratinocytes via a signaling pathway involving Stat3.
authors: Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Shinji
authors: S
authors: Mii
authors: Yoshiki
authors: Y
authors: Murakumo
authors: Naoya
authors: N
authors: Asai
authors: Mayumi
authors: M
authors: Jijiwa
authors: Sumitaka
authors: S
authors: Hagiwara
authors: Takuya
authors: T
authors: Kato
authors: Masato
authors: M
authors: Asai
authors: Atsushi
authors: A
authors: Enomoto
authors: Kaori
authors: K
authors: Ushida
authors: Sayaka
authors: S
authors: Sobue
authors: Masatoshi
authors: M
authors: Ichihara
authors: Masahide
authors: M
authors: Takahashi
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D004817:Epidermis / Q000002:abnormalities* / Q000378:metabolism / Q000473:pathology*; D055879:Gene Knock-In Techniques; D018390:Gene Targeting; D006197:Hair / Q000254:growth & development / Q000378:metabolism; D006801:Humans; D006965:Hyperplasia; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000172:deficiency* / Q000378:metabolism*; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D013737:Testis / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C548464:CD109 protein, mouse; D009363:Neoplasm Proteins; D050796:STAT3 Transcription Factor; D016212:Transforming Growth Factor beta; D001616:beta-Galactosidase