Downregulation of SMAD2, 4 and 6 mRNA and TGFbeta receptor I mRNA in lesional and non-lesional psoriatic skin.
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.
Yu
Haiyan
H
Department of Dermatology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China.
Mrowietz
Ulrich
U
Seifert
Oliver
O
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*
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