Birth Cohort Study Of Atopic Dermatitis And Effects Of H19 On Keratinocyte Differentiation

Part I A perspective birth cohort study: the prevelence of atopic dermatitis of children at age 5 years and the impact of pet exposureBackground:The prevalence of atopic dermatitis(AD)continues to increase worldwide,including China.Many studies revealed that genetic and environmental factors interaction may be the main reasons for this increase.The effect of pet exposure on the development of allergic sensitization and atopic disease is disputed.Most studies were on the western population.There was no prospective birth cohort study about the factors that contribute to the pathogenesis of AD in China.Objective:In this study,we would like to investigate the prevalence of AD among children at 5 years and the effect of domestic pet exposure at different stages on atopic dermatitis at preschool children.Methods:Shanghai Obesity and Allergy Cohort Study is an ongoing prospective birth cohort study which enrolled 1053 pairs of mothers and newborns from two tertiary hospitals between June 2012 and February 2013 in Shanghai.Children were followed up at the age of 0.5,1 and 5 years.Information on demographic information and environmental factors was collected using self-administered questionnaires.A full skin physical examination was performed by dermatologist and the diagnosis of AD was made according to three different diagnostic criteria.Skin prick test was performed on a part of volunteers.Associations between domestic pet or dog exposure and AD or allergen sensitization was analyzed by multiple logistic regression model and adjusted for lifestyle confounders.Results:At age 5 years,743(70.6%)children completed this visit including 538children who underwent a full skin physical examination and were assessed for atopic dermatitis(AD).The prevalence of atopic dermatitis was 26.6%?20.8%and 20.4%according to three different diagnostic criteria.A total of 444 children were assessed for sensitization with skin prick test.The rate of dermatophagoides pteronyssinus and dermatophagoides farinae sensitization was 44.0%and 45.4%,respectively.Mite sensitization increase the risk of AD at 5 years.Postnatal pet exposure prior to age 1was associated with a significantly lower risk of atopic dermatitis at 5 years(OR_adjusted=0.40,[95%CI:0.16-1.00])but had no association with the severity of AD.Postnatal domestic pet exposure prior to age 1 was associated with increased sensitization to dog.Conclusion:In our cohort,the prevalence of AD at age 5 years was as high as that of developed countries.Mite sensitization increase the risk of AD at 5 years.Domestic pet exposure at the early stage of life was a protective factor of AD.Part II The effect of H19 lnc RNA on the regulation of keratinocyte differentiationBackground: Aberrant differentiation of keratinocytes has been demonstrated to be associated with a number of skin diseases,including atopic dermatitis and psoriasis.A growing number of studies have showed that long noncoding RNAs(lnc RNAs)play an important part in gene regulation,however,the role of lnc RNAs in keratinocyte differentiation remains to be largely unknown.Methods: The lnc RNA-H19 was expressed transgenically,or knocked down with short hairpin RNAs,in keratinocytes.The expression of miR-130b-3p was modulated by transfection of mimics or antagomir.Luciferase reporter and RNA pull-down assays were performed to confirm the direct interaction between H19 and miR-130b-3p or between miR-130b-3p and Dsg1.Western blot and q RT-PCR assays were performed to determine the expression of genes.Results: In the present study,we demonstrated that lncRNA-H19 act as an endogenous “sponge”,which binds directly to miR-130b-3p and therefore inhibits its activity on Dsg1.Mi R-130b-3p was illustrated to inhibit keratinocyte differentiation by targeting Dsg1.H19 regulates Dsg1 expression and the consequent keratinocyte differentiation through miR-130b-3p.Conclusion: Our study casts light on a novel regulatory model of keratinocyte differentiation,which may provide new therapeutic targets for skin diseases.