Study On The Role Of Retinol Binding Protein 4 In The Pathogenesis Of Psoriasis

Background and Objective:Psoriasis is a common chronic,systemic,inflammatory disease,which has been reported to be associated with metabolic disorders.Common genetic background,overlapping chronic inflammatory processes,and abnormal immune regulation mechanisms may be the basis of psoriasis and metabolic diseases.Adipose tissue can secrete a variety of active adipokines,which play some roles in the occurrence of diabetes,obesity,metabolic syndrome,systemic sclerosis,psoriasis and other diseases.Adipokine may be a link between inflammatory diseases and metabolic diseases.Retinol Binding Protein 4(RBP4)is a newly discovered adipokine,which has a strong association with insulin resistance,type 2 diabetes,and obesity.Several studies have found that the level of serum RBP4 in patients with psoriasis differs from the normal control,but the results are inconsistent.Therefore,whether RBP4 is related to psoriasis is to be further explored.In the circulation,RBP4 is the transporter of retinol(vitamin A).Vitamin A is important for the normal formation,development and maintenance of epidermis.Retinoic acid is a metabolic intermediate of vitamin A,which regulate the proliferation and differentiation of keratinocytes.Exogenous proliferation and differentiation of keratinocytes have led to the occurrence of psoriasis.Therefore,we speculate that RBP4 and psoriasis have a certain relevance.RBP4 may affect the occurrence of psoriasis by acting on keratinocytes.In this study,we object to explore whether RBP4 is related to the occurrence of psoriasis and the possible role of RBP4 in the pathogenesis of psoriasis.Patients:Fifty-four patients with psoriasis vulgaris(PsV group),forty patients with generalized pustular psoriasis(GPP group),and twenty five patients with pigmented nevus(Control group)were enrolled.They were all patients in the department of dermatology at Peking Union Medical College Hospital from April 2013 to October 2015.Patients with body mass index(BMI)greater than 35 and patients combined with other chronic inflammatory diseases,metabolic diseases,tumor were excluded.We collected all the patients’ serum after fasting for 12 hours.We chose another twelve PsV patients and fourteen GPP patients to take the skin lesions.We chose another nine patients with pigmented nevus and took normal skin tissue on the edge of their nevus.Methods:1.The levels of serum RBP4 in 54 patients with PsV,40 patients with GPP and 25 controls were detected by enzyme-linked immunosorbent assay(ELISA).We analyzed the correlation between serum RBP4 levels and the clinical characteristics of patients with psoriasis.2.Real-time quantitative PCR(RT-PCR)was used to detect the levels of RBP4 mRNA in skin tissue of 12 patients with PsV,14 patients with GPP lesions and 9 controls.3.Immunohistochemistry was used to detect the levels of RBP4 protein in skin tissue of 8 patients with PsV,10 patients with GPP lesions and 8 controls.4.We cultured HaCaT cells and added different concentrations of RBP4 protein.The levels of IL-1β and IL-17A in the culture supernatant of HaCaT cells were detected by ELISA after 48h.Results:1.The level of serum RBP4 in GPP group was significantly lower than that in control group(p = 0.018).There was no significant difference in serum RBP4 level between PsV group and control group.The level of serum RBP4 in GPP patients was positively correlated with HOMA-IR(r = 0.503,p<0.01),TC(r = 0.374,p<0.05),and HDL-C(r = 0.333,p<0.05).There was no significant correlation between serum RBP4 level and age,total course of disease,BMI,GPP severity score,TG,LDL-C and CRP in GPP patients(r<0.3,p<0.05).There was no significant correlation between serum RBP4 level and age,total course,BMI,PASI score,HOMA-IR,blood lipids and CRP in PsV patients(r<0.3,p<0.05).2.The levels of RBP4 protein in skin lesions in PsV group and GPP group were significantly lower than those in the control group,and there was significant difference between the three groups(P = 0.009).There was no significant difference in the levels of RBP4 mRNA in skin lesions between GPP group,PsV group and the control group(p-0.155,0.179).3.IL-1β and IL-17A secretion of HaCaT cells was significantly lower than the control group when different concentrations(5μg/ml,10μg/ml,25μg/ml,50μg/ml)of RBP4 were applied for 48h.Conclusion:1.RBP4 is associated with the occurrence of psoriasis and is more closely related to GPP.2.Inhibiting the secretion of IL-1β and IL-17A from HaCaT cells to prevent the occurrence of psoriasis may be a role of RBP4 in the pathogenesis of psoriasis.3.RBP4 may be a protective factor that prevents the occurrence of psoriasis.