Transforming growth factor（TGF）-β signaling plays an important role in the pathogenesis of psoriasis. CD109, a novel TGF-β co-receptor, which inhibits TGF-β signaling by enhancing Smad7-dependent degradation of T...Transforming growth factor（TGF）-β signaling plays an important role in the pathogenesis of psoriasis. CD109, a novel TGF-β co-receptor, which inhibits TGF-β signaling by enhancing Smad7-dependent degradation of TGF-β type Ⅰ receptor（TGF-β RⅠ）, is abnormally expressed in psoriasis. To date, the expression of Smad7 and the correlation between CD109 and Smad7 expression in psoriasis have not been fully elucidated. This study was designed to investigate the expression and the correlation of CD109 and TGF-β signaling associated proteins in psoriasis and their roles in the pathogenesis of psoriasis. Thirty-two psoriasis specimens were subjected to immunohistochemical staining for CD109, Smad7, TGF-β RⅠ and Ki67. Ten normal skin（NS） specimens served as controls. The positive expression rate（% positive cells） of Smad7 and Ki67 in psoriasis was significantly higher than in NS（62.6%±19.9% vs. 17.2%±4.4%, and 50.7%±14.3% vs. 19.5%±3.2%, respectively, P〈0.001）, and the expression levels of CD109 and TGF-β RⅠ were reduced significantly in psoriasis as compared with NS（8.1%±6.7% vs. 35.8%±6.7% and 27.3%±3.4% vs. 3.0%±3.4%, respectively, P〈0.001）. There were significantly negative correlations between CD109 and Smad7（r=-0.831, P〈0.01）. These findings indicated that CD109 might play a certain role in the pathogenesis of psoriasis. Lower expression of CD109 and TGF-β RⅠ was highly correlated with higher expression of Smad7 and Ki67, suggesting that CD109 may induce the pathogenesis of psoriasis through Smad7-mediated degradation of TGF-β RⅠ, and lead to the termination of TGF-β signaling.展开更多
Summary： 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...Summary： 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 USP 15 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 USP 15 small interfering RNA （USP 15 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- Ⅰ expression, and between TβR- Ⅰ and Smad7 expression in psoriasis. After transfection of USP15 siRNA in Hacat ceils, the expression ofTβR- Ⅰ mRNA was up-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 USP 15 to take part in the development of psoriasis.展开更多
基金supported by the National Natural Science Foundation of China(No.81101191and No.30972654)
文摘Transforming growth factor（TGF）-β signaling plays an important role in the pathogenesis of psoriasis. CD109, a novel TGF-β co-receptor, which inhibits TGF-β signaling by enhancing Smad7-dependent degradation of TGF-β type Ⅰ receptor（TGF-β RⅠ）, is abnormally expressed in psoriasis. To date, the expression of Smad7 and the correlation between CD109 and Smad7 expression in psoriasis have not been fully elucidated. This study was designed to investigate the expression and the correlation of CD109 and TGF-β signaling associated proteins in psoriasis and their roles in the pathogenesis of psoriasis. Thirty-two psoriasis specimens were subjected to immunohistochemical staining for CD109, Smad7, TGF-β RⅠ and Ki67. Ten normal skin（NS） specimens served as controls. The positive expression rate（% positive cells） of Smad7 and Ki67 in psoriasis was significantly higher than in NS（62.6%±19.9% vs. 17.2%±4.4%, and 50.7%±14.3% vs. 19.5%±3.2%, respectively, P〈0.001）, and the expression levels of CD109 and TGF-β RⅠ were reduced significantly in psoriasis as compared with NS（8.1%±6.7% vs. 35.8%±6.7% and 27.3%±3.4% vs. 3.0%±3.4%, respectively, P〈0.001）. There were significantly negative correlations between CD109 and Smad7（r=-0.831, P〈0.01）. These findings indicated that CD109 might play a certain role in the pathogenesis of psoriasis. Lower expression of CD109 and TGF-β RⅠ was highly correlated with higher expression of Smad7 and Ki67, suggesting that CD109 may induce the pathogenesis of psoriasis through Smad7-mediated degradation of TGF-β RⅠ, and lead to the termination of TGF-β signaling.
基金supported by grants from National NaturalScience Foundation of China(No.81101191 and No.30972654)
文摘Summary： 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 USP 15 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 USP 15 small interfering RNA （USP 15 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- Ⅰ expression, and between TβR- Ⅰ and Smad7 expression in psoriasis. After transfection of USP15 siRNA in Hacat ceils, the expression ofTβR- Ⅰ mRNA was up-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 USP 15 to take part in the development of psoriasis.
