title: Downregulation of SMAD2, 4 and 6 mRNA and TGFbeta receptor I mRNA in lesional and non-lesional psoriatic skin.
abstract: Transforming growth factor beta (TGFbeta) has been suggested to be an effective inhibitor of the increased keratinocyte proliferation in psoriasis. Three TGFbeta isoforms are described (TGFbeta1, 2 and 3), signalling via a heteromeric receptor complex of TGFbetaRI and TGFbetaRII. Receptor binding activates SMAD2, 3 and 4, which translocate into the nucleus and regulate TGFbeta-responsive genes. SMAD6 and 7 proteins represent a negative feedback loop inhibiting the TGFbeta-SMAD signalling path-way. As TGFbeta1 overexpression inhibits keratinocyte proliferation, the aim of this study was to investigate with real-time RT-PCR the expression of TGFbeta1, 2 and 3, TGFbetaRI and TGFbetaRII and SMAD2, 3, 4, 6 and 7 in lesional and non-lesional psoriatic skin from 13 patients with chronic plaque-type psoriasis as compared to skin from 10 healthy subjects . The study data demonstrate significantly downregulated TGFbetaRI and SMAD2, 4 and 6 mRNA expression in lesional and non-lesional psoriatic skin. SMAD7 mRNA expression was significantly decreased in lesional psoriatic skin compared with both non-lesional psoriatic skin and healthy skin. A significant TGFbeta3 and TGFbetaRII mRNA upregulation exclusively in non-lesional psoriatic skin but no significant difference in the expression of TGFbeta1 and 2 was found. The results of this study suggest that the expression of TGFbeta isoforms, receptors and SMADs may be involved in the increased proliferation of keratinocytes in psoriatic skin.
authors.affiliation: Department of Dermatology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Yu
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mrowietz
authors.forename: Oliver
authors.initials: O
authors.lastname: Seifert
mesh_terms: D000328:Adult; D015536:Down-Regulation / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011565:Psoriasis / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D051899:Smad2 Protein / Q000378:metabolism*; D051901:Smad4 Protein / Q000378:metabolism*; D051905:Smad6 Protein / Q000235:genetics*; D051906:Smad7 Protein / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; C497782:SMAD2 protein, human; C497796:SMAD4 protein, human; C497802:SMAD6 protein, human; C497806:SMAD7 protein, human; D051899:Smad2 Protein; D051901:Smad4 Protein; D051905:Smad6 Protein; D051906:Smad7 Protein; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I