Expression Of TGF-β Receptor-activated Smads And Common-partner Smad In Psoriatic Lesions

Background: Transforming growth factorβ(TGF-β) exerts an important role in maintaining the homeostasis in epidermis by inhibiting proliferation of keratinocytes. The intracellular signaling of TGF-βfrom the membrane receptors to nucleus is mediated and regulated by the Smad proteins, which have been grouped into three distinct classes depending on their sequence identity and function in the signal transduction: the receptor-activated Smads (R-Smads), the common-partner Smad (Smad4) and the inhibitory Smads (I-Smads).Psoriasis vulgaris is a common chronic, relapsing, and inflammatory skin disorder. Many cytokines are involved in the pathogenesis of psoriasis vulgaris. The blockade of TGF-βsignaling pathway may contribute to the formation of psoriatic lesions. The altered expression levels of some important components in TGF-β/Smad signaling pathway in the epidermis of psoriatic lesions were found in recent years, including decreased expressions of TGF-βand its receptors, and increased expressions of Smad ubiquitination regulatory factors (Smurf1 and Smurf2) and one of the inhibitory Smads——Smad7.Based on the findings mentioned above, we suppose that altered expression of some important members in the Smad family may also exist in the epidermis of psoriatic lesions. Whether the expression levels of TGF-βreceptor-activated Smads (such as Smad2 and Smad3) and the common-partner Smad——Smad4 are altered in psoriasis vulgaris lesions remains obscure.Objective: To investigate the expressions of TGF-βreceptor-activated Smads and common-partner Smad in psoriasis vulgaris lesions, for further insights into the correlation between alterations in the TGF-βsignaling pathway and epidermal hyperplasia in this disease.Method: Reverse transcription (RT) and quantitative real time polymerase chain reaction (Real time PCR) technique was utilized to assess the expresions of Smad2, Smad3 and Smad4 mRNA in psoriasis vulgaris lesions and normal skin specimens. The expresions of Smad1/2/3, p-Smad2/3 and Smad4 proteins in psoriasis vulgaris lesions and normal skin specimens were detected using EliVision^TMplus immunohistochemical technique.Results: Down-regulated expressions of Smad2, Smad3 and Smad4 mRNA in psoriasis vulgaris lesions were demonstrated by RT and Real time PCR, in comparison with those in normal skin specimens. Immunohistochemial analyses revealed decreased expressions of Smad1/2/3, p-Smad2/3 and Smad4 protein in psoriatic epidermis compared with those in normal epidermis.Conclusion: The down-regulated expression of the receptor-activated Smads and the common-partner Smad in TGF-β/Smad signaling pathway existed in the epidermis of psoriasis vulgaris lesions. The decreased expression of these Smads might contribute to the blockade of TGF-βsignaling. Under the integrated action of other proinflammatory factors and keratinocyte-stimulating factors,keratinocytes lacking TGF-β-mediated inhibition might actively proliferate and mature rapdly so that develop pathological changes characterized by aberrant epidermal hyperplasia in psoriasis vulgaris. Taken together with the prestnt study and previous studies on TGF-β/Smad signaling pathway in psoriatic lesions, the findings suggest that multiple abnormalities in TGF-β/Smad signaling pathway exist in psoriatic epidermis.