title: Association of down-regulation of CD109 expression with up-expression of Smad7 in pathogenesis of psoriasis.
abstract: Transforming growth factor (TGF)-β signaling plays an important role in the pathogenesis of psoriasis. CD109, a novel TGF-β co-receptor, which inhibits TGF-β signaling by enhancing Smad7-dependent degradation of TGF-β type I receptor (TGF-β RI), is abnormally expressed in psoriasis. To date, the expression of Smad7 and the correlation between CD109 and Smad7 expression in psoriasis have not been fully elucidated. This study was designed to investigate the expression and the correlation of CD109 and TGF-β signaling associated proteins in psoriasis and their roles in the pathogenesis of psoriasis. Thirty-two psoriasis specimens were subjected to immunohistochemical staining for CD109, Smad7, TGF-β RI and Ki67. Ten normal skin (NS) specimens served as controls. The positive expression rate (% positive cells) of Smad7 and Ki67 in psoriasis was significantly higher than in NS (62.6%±19.9% vs. 17.2%±4.4%, and 50.7%±14.3% vs. 19.5%±3.2%, respectively, P<0.001), and the expression levels of CD109 and TGF-β RI were reduced significantly in psoriasis as compared with NS (8.1%±6.7% vs. 35.8%±6.7% and 27.3%±3.4% vs. 3.0%±3.4%, respectively, P<0.001). There were significantly negative correlations between CD109 and Smad7 (r=-0.831, P<0.01). These findings indicated that CD109 might play a certain role in the pathogenesis of psoriasis. Lower expression of CD109 and TGF-β RI was highly correlated with higher expression of Smad7 and Ki67, suggesting that CD109 may induce the pathogenesis of psoriasis through Smad7-mediated degradation of TGF-β RI, and lead to the termination of TGF-β signaling.
authors.affiliation: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Liu
authors.affiliation: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Ai-Ping
authors.initials: AP
authors.lastname: Feng
authors.affiliation: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: He
authors.affiliation: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Lian
authors.affiliation: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Hu
authors.affiliation: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Jia-Wen
authors.initials: JW
authors.lastname: Li
authors.affiliation: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Ya-Ting
authors.initials: YT
authors.lastname: Tu
authors.affiliation: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. csjlsh@sina.com.
authors.forename: Shan-Juan
authors.initials: SJ
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D015536:Down-Regulation; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011565:Psoriasis / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D051906:Smad7 Protein / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; C120523:CD109 protein, human; D058851:GPI-Linked Proteins; D009363:Neoplasm Proteins; C497806:SMAD7 protein, human; D051906:Smad7 Protein; D016212:Transforming Growth Factor beta
keywords: CD109; Smad7; psoriasis; signal transduction; transforming growth factor beta
references.citation: J Huazhong Univ Sci Technolog Med Sci. 2014 Jun;34(3):415-9
references.pmid: 24939309
references.citation: J Dermatol Sci. 2003 Oct;33(1):7-16
references.pmid: 14527734
references.citation: Oncogene. 2010 Apr 15;29(15):2181-91
references.pmid: 20101215
references.citation: J Biol Chem. 2006 Jun 23;281(25):17069-75
references.pmid: 16641086
references.citation: J Biol Chem. 2001 Apr 20;276(16):12477-80
references.pmid: 11278251
references.citation: Cell. 2003 Jun 13;113(6):685-700
references.pmid: 12809600
references.citation: Exp Dermatol. 2011 Aug;20(8):627-32
references.pmid: 21539622
references.citation: Oncogene. 2004 Apr 29;23(20):3716-20
references.pmid: 15116102
references.citation: J Cell Physiol. 1998 Sep;176(3):553-64
references.pmid: 9699508
references.citation: Growth Factors. 2011 Oct;29(5):196-202
references.pmid: 21740331
references.citation: Onco Targets Ther. 2013 Jun 07;6:621-7
references.pmid: 23776335
references.citation: Mol Cell. 2000 Dec;6(6):1365-75
references.pmid: 11163210
references.citation: Pharmacol Ther. 2001 Jul;91(1):1-34
references.pmid: 11707292
references.citation: J Dermatol Sci. 2010 Feb;57(2):140-2
references.pmid: 20034764
references.citation: Curr Pharm Biotechnol. 2011 Dec;12(12):2165-75
references.pmid: 21619542
references.citation: Tumour Biol. 2014 Sep;35(9):8379-85
references.pmid: 24935472
references.citation: Int J Burns Trauma. 2012;2(1):18-28
references.pmid: 22928164
references.citation: FASEB J. 2006 Jul;20(9):1525-7
references.pmid: 16754747
references.citation: Blood. 2002 Mar 1;99(5):1683-91
references.pmid: 11861284
references.citation: Arthritis Res Ther. 2012 Jun 13;14(3):R144
references.pmid: 22694813
references.citation: J Cell Biochem. 2012 Jan;113(1):238-46
references.pmid: 21898545
references.citation: Biochim Biophys Acta. 2011 May;1813(5):742-53
references.pmid: 21295082
references.citation: N Engl J Med. 2009 Jul 30;361(5):496-509
references.pmid: 19641206
references.citation: Clin Exp Pharmacol Physiol. 2014 Nov;41(11):921-32
references.pmid: 25132073
references.citation: J Dermatol. 2010 Jan;37(1):11-25
references.pmid: 20175837
references.citation: Br J Dermatol. 1998 Jan;138(1):57-62
references.pmid: 9536223
references.citation: Postepy Biochem. 2008;54(3):264-73
references.pmid: 19112825