Yu Haiyan, Mrowietz Ulrich, Seifert Oliver
Department of Dermatology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China.
Acta Derm Venereol. 2009;89(4):351-6. doi: 10.2340/00015555-0634.
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.
转化生长因子β（TGFβ）被认为是银屑病中角质形成细胞增殖增加的有效抑制剂。已描述了三种TGFβ亚型（TGFβ1、2和3），它们通过TGFβRI和TGFβRII的异源受体复合物进行信号传导。受体结合激活SMAD2、3和4，它们转移到细胞核并调节TGFβ反应性基因。SMAD6和7蛋白代表抑制TGFβ-SMAD信号通路的负反馈环。由于TGFβ1过表达抑制角质形成细胞增殖，本研究的目的是通过实时逆转录聚合酶链反应（RT-PCR）研究13例慢性斑块型银屑病患者的皮损和非皮损银屑病皮肤中TGFβ1、2和3、TGFβRI和TGFβRII以及SMAD2、3、4、6和7的表达，并与10名健康受试者的皮肤进行比较。研究数据表明，皮损和非皮损银屑病皮肤中TGFβRI和SMAD2、4及6的mRNA表达显著下调。与非皮损银屑病皮肤和健康皮肤相比，皮损银屑病皮肤中SMAD7 mRNA表达显著降低。仅在非皮损银屑病皮肤中发现TGFβ3和TGFβRII mRNA显著上调，但TGFβ1和2的表达无显著差异。本研究结果表明，TGFβ亚型、受体和SMAD的表达可能与银屑病皮肤中角质形成细胞的增殖增加有关。
