The Expression Of Sirt1and Connexin In Psoriatic Lesions And The Effects Of Sirt1on Connexin

Background and Objectives:Psoriasis is a kind of common chronic inflammatory skin disease, whose incidence is highe. It is easy to relapse, has longe duration and violates young adults frequently. The influence on the patients’physical and mental health and quality of life is great. It is one of the key research fields in skin disease.Generally, psoriasis is a multi-gene genetic disease with interaction between genetic factors and environmental factors, in which heredity, immune, infection, environment, mental, metabolism, endocrine and other factors play an important role. However, the etiology and pathogenesis of psoriasis are still not completely clear. In recent years, studies have found that patients with psoriasis have different degrees of skin barrier dysfunction, and the expression and distribution of connexins change significantly. Tight junctions and adherens junctions that are composed by tight junction protein and adherens junction protein are important components that form the connections between epidermal keratinocytes. They play an important role in the maintenance of the skin mechanical barrier, permeability barrier, cell adhesion, polarity and other important functions. The regulation of tight junction protein and adherens junction protein is mainly controlled by genetic and environmental factors. Environmental factor inducing histone acetylation and deacetylation reaction is an important epigenetic regulation, which can influence skin connexin by regulating the expression of specific genes. Silent information regulator proteinl is a kind of very important histone deacetylase in the body, participateing in the regulation of histone deacetylation.This paper is to study the expression of Sirtl, tight junctions and adherens junction protein in cutaneous lesion of psoriasis, and the effects of Sirtl expression and activation on the expression of tight junctions and adherens junction protein in HaCaT keratinocytes in vitro, then to explore their possible role and clinical significance.Methods:(l)Psoriatic lesion tissue experiment:Immunohistochemistry and Immunofluorescence were used to detect the expression and localization of Sirtl, tight junction protein (occludin, ZO-1), adherens junction protein (E-cadherin) in cutaneous lesion of psoriasis, and in normal human skin tissues as control;(2)Cytological experiment:RT-PCR was used to detect mRNA levels of Sirtl in HaCaT cells treated with Sirtl activator resveratrol or its inhibitor nicotinamide; The expressions of Sirtl, tight junction proteins and adhesion junction proteins were assessed with western blotting.Results:(1)Psoriatic lesion tissue experiment:Compared with normal human skin tissue, Sirtl which expressed in psoriatic tissue decreased, while the expression levels of connexin occludin, ZO-1, E-cadherin significantly increased.(2)Cytological experiment:Compared with the control group, resveratrol could significantly increase the expression of Sirtl both in mRNA and protein levels. Sirtl activation decreased the expression of cell tight junction proteins and adhesion junction proteins in HaCaT cells.Conclusion:Sirtl may have a role in decreasing the expression of cell junction protein in psoriatic keratinocyte.