Expression of USP15, TβR-I and Smad7 in psoriasis

Abstract

The deubiquitinating enzyme ubiquitin specific peptidase 15 (USP15) is regarded as a regulator of TGFβ signaling pathway. This process depends on Smad7, the inhibitory factor of the TGFβ signal, and type I TGFβ receptor (TβR-I), one of the receptors of TGFβ. The expression level of USP15 seems to play vital roles in the pathogenesis of many neoplasms, but so far there has been no report about USP15 in psoriasis. In this study, immunohistochemical staining of USP15, TβR-I and Smad7 was performed in 30 paraffin-embedded psoriasis specimens and 10 normal specimens to investigate the expression of USP15, TβR-I and Smad7 in psoriasis and to explore the relevance among them. And USP15 small interfering RNA (USP15 siRNA) was used to transfect Hacat cells to detect the mRNA expression of TβR-I and Smad7. Of 30 cases of psoriasis in active stage, 28, 24 and 26 cases were positive for USP15, TβR-I and Smad7 staining, respectively. The positive rates of USP15 and Smad7 were significantly higher in psoriasis specimens than in normal skin specimens (44.1%±26.0% vs. 6.1%±6.6%, 47.2%±27.1% vs. 6.6%±7.1%), and positive rate of TβR-I (20.3%±22.2%) in psoriasis was lower than that in normal skin specimens (46.7%±18.2%). There was a significant positive correlation between USP15 and Smad7 expression, and significant negative correlations between USP15 and TβR-expression, an I d between TβR- and Smad7 expression I in psoriasis. After transfection of USP15 siRNA in Hacat cells, the expression of TβR-mRNA was up I -regulated and that of Smad7 was down-regulated. It is concluded that USP15 may play a role in the pathogenesis of psoriasis through regulating the TβR-I/Smad7 pathway and there may be other cell signaling pathways interacting with USP15 to take part in the development of psoriasis.

Smad7 in psoriasis vulgaris patients: A clinical and immunohistochemical study

“…In the present study, biopsies from patients showed positive expression of Smad7 in the cytoplasm and nucleus of epidermal keratinocytes, while only nuclear expression was present in control groups. Feng et al 16 found also that Smad7 was expressed in cytoplasm and some nuclei of epidermal cells in psoriasis. In agreement with this finding, Tang et al 15 stated that Smad7 resides mainly in the nucleus at basal state and transfers to the cytoplasm upon TGF‐J3 stimulation.…”

“…To the best of our knowledge, the study of the role of Smad7 protein in psoriasis was explored in only few previous studies 16,18,19 . Liu et al 20 used the same previous results of Feng and their research team 16 and investigated the correlation between CD109 and Smad7 expression in psoriasis.…”

“…To the best of our knowledge, the study of the role of Smad7 protein in psoriasis was explored in only few previous studies 16,18,19 . Liu et al 20 used the same previous results of Feng and their research team 16 and investigated the correlation between CD109 and Smad7 expression in psoriasis. Also, few previous studies have investigated the role of other Smads and TGFβ/Smads signaling in psoriasis at the immunohistochemical and molecular levels and showed controversial results 21‐23 …”

“…Stained slides were examined and scored blindly by a pathologist without recognition of patients’ clinical data. Positive expression was assigned when evident cytoplasmic and/or nuclear staining was found 15,16 . The percentage of the positive cells was subjectively assessed at 200× magnification field.…”

Ubiquitination of RORγt at Lysine 446 Limits Th17 Differentiation by Controlling Coactivator Recruitment

“…We demonstrated here that recruitment of SRC1 is regulated by ubiquitination of K446, suggesting that drugs targeting this RORγt ubiquitination pathway can inhibit RORγt activity by limiting co-activator SRC1 recruitment. Interestingly, a recent report shows that USP15 is up-regulated in psoriasis, supporting the possible role of USP15 in this Th17-mediated autoimmune disease (57). We expect that USP15 inhibitors will alleviate Th17-mediated autoimmunity including psoriasis via blocking the recruitment of SRC1.…”