Downregulation of erythroid differentiation regulator 1 (Erdr1) plays a critical role in psoriasis pathogenesis

Abstract

c.474G>A, was considered to be responsible for the milder phenotype in our patient.Our RT-PCR for c.474G>A detected three transcripts, including two out-of-frame transcripts and an in-frame transcript. The inframe transcript displayed expression level equivalent to that of normal protein.In conclusion, we found that c.474G>A synonymous mutation causes abnormal splicing, and the in-frame mutant transcript accounts for the mild phenotype in our patient. The results further expanded the mutation spectrum in NS and demonstrated the importance of RNA analysis to precisely understand molecular basis of genodermatosis. AcknowledgementsSee Data S2 for details. Author contributionsS.N. and T.H. (Hamada) designed the study. S.N. and K.T. performed the study and analysed the data. Y.O, K.H and M.M. gave clinical and pathological information. P.F., GD.Z, DC and G.Z. provided the antibodies against the D7-12 and D14-15 of LEKTI. RP.K helped to make figures. S.N., K.T. and T.H (Hashimoto) wrote the paper. Conflict of interestThe authors have declared no conflicting interests. Supporting InformationAdditional Supporting Information may be found online in the supporting information tab for this article:Data S1. Methods. BackgroundPsoriasis is a common chronic skin disease which is accompanied by chronic inflammation. Various proinflammatory cytokines including IL-18, TNF-a and IL-12, which are elevated in psoriatic lesional skin and have critical roles in psoriasis pathogenesis, have been identified and targeted for psoriasis treatment (1). In particular, IL-18 has been classified as a biomarker for psoriasis activity with other cytokines (2). It has been confirmed that serum IL-18 concentration and cutaneous IL-18 expression in the skin is significantly elevated in psoriasis patients, compared with normal healthy donors, and there is a positive correlation between serum IL-18 expression and the Psoriasis Area and Severity Index (PASI) (2,3). Questions addressedIn our previous studies, we found that erythroid differentiation regulator 1 (Erdr1) is negatively regulated by IL-18 in mouse melanoma, suggesting the opposite effects of Erdr1 with IL-18 (4). In this study, we investigated whether Erdr1 is negatively regulated by IL-18 in human keratinocytes and evaluated the downregulation of Erdr1 in psoriasis to determine whether Erdr1 acts as a novel regulator for psoriasis pathogenesis. Methods Letter to the Editor Experimental designFor full details of materials and methods, see Data S1. ResultsTo determine whether Erdr1 expression has an inverse correlation with IL-18 expression in keratinocytes, HaCaT cells were transfected with IL-18 siRNA or negative siRNA. The relative Erdr1 expression level is significantly higher in IL-18 siRNA transfectants incubated for 48 h than in IL-18 siRNA transfectants incubated for 24 h, showing much more increase of Erdr1 in accordance with more decrease of IL-18 (Fig. 1a, b). Densitometry data show approximately a twofold increase in Erdr1 expression after IL-18 siRNA transfection, indicating ...

Erythroid Differentiation Regulator 1 as a Novel Biomarker for Hair Loss Disorders

“…Moreover, T helper 1 cytokines in AA are implicated in the dysregulation of the hair follicle’s immune homeostasis [9]. Erdr1 is negatively regulated by IL-18 [16], an IFN-γ inducing molecule. Therefore, we proposed that Erdr1 downregulation might be involved in the inflammatory cascade in AA.…”

“…In addition, Lee et al [15] have reported that patients with AA have abnormal serum IL-18 levels. In our previous study, we have observed negative correlations between IL-18 and erythroid differentiation regulator 1 (Erdr1) in human keratinocytes [16]. Recently, it has been reported that Erdr1 plays an important role in the inflammatory process via regulating the immune system in various cutaneous chronic inflammatory disorders, such as psoriasis and rosacea [16,17].…”

Roles of Erythroid Differentiation Regulator 1 (Erdr1) on Inflammatory Skin Diseases

“…Because serum IL-18 concentration is linked to psoriasis severity (PASI), IL-18 might be considered as a possible biomarker of psoriasis [24]. In HaCaT cells, Erdr1 expression is also inversely correlated with IL-18 [59]. Kim et al compared Erdr1 expression in skin tissues from human psoriasis patients and healthy volunteers.…”

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“…Based on our previous finding that Erdr1 expression is negatively correlated with that of IL-18 [6], we investigated whether IL-18 expression in synovial tissue was decreased in the rErdr1-treated group. , with the exception of the negative control (normal) group.…”