RAS-association domain family 1A regulates the abnormal cell proliferation in psoriasis via inhibition of Yes-associated protein.
RAS-association domain family 1A regulates the abnormal cell proliferation in psoriasis via inhibition of Yes-associated protein.
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RAS 相关结构域家族 1A 通过抑制 Yes 相关蛋白调节银屑病中的异常细胞增殖
DOI：
10.1111/jcmm.16489
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发表时间：
2021-06
影响因子：
5.3
通讯作者：
Chen D
中科院分区：
文献类型：
--
作者：
Jia J;Wang N;Zheng Y;Mo X;Zhang Y;Ye S;Liu J;Yan F;Li H;Chen D
银屑病是一种发病率高、复发率高的慢性炎症性皮肤病，但其确切发病机制和病因尚不清楚。本研究旨在分析上游负调节因子RAS相关结构域家族1A（RASSF 1A）对银屑病患者Yes相关蛋白（雅普）的影响。22例银屑病患者和19名健康对照者的皮肤病变被使用。采用M5（IL-1α、IL-17、IL-22、TNF-α和制瘤素M）刺激的人表皮角质形成细胞建立银屑病细胞模型。用外用咪喹莫特治疗的BALB/c小鼠用于建立银屑病小鼠模型。随着RASSF 1A甲基化水平的升高，其在银屑病患者和小鼠模型中的表达降低。添加甲基化抑制剂5-Aza-CdR或RASSF 1A-过表达慢病毒载体可增加RASSF 1A并减少雅普表达;同时改善皮肤病变，减少细胞增殖，诱导细胞周期停滞在G 0/G1期，增加细胞凋亡，降低炎性细胞因子以及ERK、STAT 3和NF-κB信号通路的活性。提示RASSF 1A可能通过抑制雅普的表达而发挥治疗银屑病的作用。基于这些发现，可以抑制甲基化或增加RASSF 1A表达的靶向药物可能对治疗银屑病有用。
Psoriasis is a chronic, inflammatory skin disease with a high incidence and recurrence; however, its exact pathogenesis and aetiology remain unclear. This study aimed to analyse the effect of the upstream negative regulator RAS‐association domain family 1A (RASSF1A) on Yes‐associated protein (YAP) in psoriasis. Skin lesions of 22 patients with psoriasis and 19 healthy controls were used. Human epidermal keratinocytes stimulated by M5 (IL‐1α, IL‐17, IL‐22, TNF‐α and oncostatin M) were used to establish a psoriatic cell model. BALB/c mice treated with topical imiquimod were used to establish a psoriatic mouse model. As the methylation level of RASSF1A increased, its expression in psoriatic patients and mice model decreased. Addition of the methylation inhibitor 5‐Aza‐CdR or RASSF1A‐overexpressing lentivirus vector increased RASSF1A and reduced YAP expression; meanwhile improved skin lesions, reduced cell proliferation, induced cell cycle arrest in the G0/G1 phase, increased apoptosis, reduced inflammatory cytokines and activities of ERK, STAT3 and NF‐κB signalling pathways. The results indicated that RASSF1A could play a role in the treatment of psoriasis by inhibiting YAP expression. Based on these findings, targeted drugs that can inhibit the methylation or increase the expression of RASSF1A may be useful for treating psoriasis.
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影响因子：
2.3
作者：
Boehncke, Wolf-Henning
通讯作者：
Boehncke, Wolf-Henning
影响因子：
64.5
作者：
Dong, Jixin;Feldmann, Georg;Pan, Duojia
通讯作者：
Pan, Duojia
RASSF1A的Sarah域及其肿瘤抑制功能。
DOI：
10.1155/2012/196715
发表时间：
2012
期刊：
Molecular biology international
影响因子：
--
作者：
Dittfeld C;Richter AM;Steinmann K;Klagge-Ulonska A;Dammann RH
通讯作者：
Dammann RH
影响因子：
3.7
作者：
Rabeony H;Petit-Paris I;Garnier J;Barrault C;Pedretti N;Guilloteau K;Jegou JF;Guillet G;Huguier V;Lecron JC;Bernard FX;Morel F
通讯作者：
Morel F
影响因子：
16
作者：
Basu, S;Totty, NF;Downward, J
通讯作者：
Downward, J