Content » Vol 89, Issue 4

Investigative Report

Downregulation of SMAD2, 4 and 6 mRNA and TGFβ Receptor I mRNA in Lesional and Non-lesional Psoriatic Skin

Haiyan Yu, Ulrich Mrowietz and Oliver Seifert
DOI: 10.2340/00015555-0634

Abstract

Transforming growth factor beta (TGFβ) has been suggested to be an effective inhibitor of the increased keratinocyte proliferation in psoriasis. Three TGFβ isoforms are described (TGFβ1, 2 and 3), signalling via a heteromeric receptor complex of TGFβRI and TGFβRII. Receptor binding activates SMAD2, 3 and 4, which translocate into the nucleus and regulate TGFβ-responsive genes. SMAD6 and 7 proteins represent a negative feedback loop inhibiting the TGFβ-SMAD signalling path­way. As TGFβ1 overexpression inhibits keratinocyte proliferation, the aim of this study was to investigate with real-time RT-PCR the expression of TGFβ1, 2 and 3, TGFβRI and TGFβRII 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 TGFβRI 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 TGFβ3 and TGFβRII mRNA upregulation exclusively in non-lesional psoriatic skin but no significant difference in the expression of TGFβ1 and 2 was found. The results of this study suggest that the expression of TGFβ isoforms, receptors and SMADs may be involved in the increased proliferation of keratinocytes in psoriatic skin.

Significance

Supplementary content

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