Department of Medical Biochemistry and Molecular Biology, Cairo University, Cairo, Egypt.
Eur J Dermatol. 2012 Mar-Apr;22(2):218-24. doi: 10.1684/ejd.2012.1649.
Direct intercellular signaling, which controls keratinocyte behavior, proliferation and differentiation, occurs through gap junctions. Altered expression of connexins may play a role in the development of psoriatic lesions.
We estimated connexin 26 (Cx26) mRNA in psoriatic patients and investigated whether the standard therapeutic modalities (methotrexate and PUVA) exert their anti-psoriatic activity partially through altering Cx26 mRNA levels. We also detected Cx26 in skin biopsies by immunohistochemistry. RT-PCR measured Cx26 mRNA levels in 24 chronic plaque psoriasis patients. Group A received intramuscular methotrexate and group B was treated by PUVA for ten weeks, each followed by measurement of Cx26 mRNA levels and immunohistochemistry. Twelve healthy volunteers served as controls.
Cx26 mRNA expression was significantly higher in the patients before treatment than in controls (P<0.001). Post treatment levels were significantly lower than pre-treatment levels (P<0.001), however, significantly higher than in controls (P<0.001). Methotrexate and PUVA caused significant reductions in Cx26 mRNA expression (P=0.002, P=0.028 respectively). Post treatment levels were slightly significantly lower in the methotrexate group than in the PUVA group (P=0.046). The reduction in Cx26 mRNA expression was significantly positively correlated with the clinical improvement of the psoriatic plaque (P=0.002). Immunostaining of Cx26 decreased after treatment.
Altered expression of the gap junction protein Cx26 may have a role in the development of the psoriatic phenotype. Both methotrexate and PUVA significantly lowered the expression of Cx26 mRNA and protein.
直接的细胞间信号传导控制角质形成细胞的行为、增殖和分化,是通过缝隙连接进行的。连接蛋白的表达改变可能在银屑病病变的发展中起作用。
我们估计了银屑病患者的连接蛋白 26(Cx26)mRNA,并研究了标准治疗方法(甲氨蝶呤和 PUVA)是否通过改变 Cx26 mRNA 水平部分发挥其抗银屑病活性。我们还通过免疫组织化学检测了皮肤活检中的 Cx26。RT-PCR 测量了 24 例慢性斑块状银屑病患者的 Cx26 mRNA 水平。A 组接受肌肉内甲氨蝶呤治疗,B 组接受 PUVA 治疗十周,然后分别测量 Cx26 mRNA 水平和免疫组织化学。12 名健康志愿者作为对照。
治疗前患者的 Cx26 mRNA 表达明显高于对照组(P<0.001)。治疗后水平明显低于治疗前(P<0.001),但明显高于对照组(P<0.001)。甲氨蝶呤和 PUVA 导致 Cx26 mRNA 表达显著降低(P=0.002,P=0.028 分别)。与 PUVA 组相比,甲氨蝶呤组的 Cx26 mRNA 表达水平略低(P=0.046)。Cx26 mRNA 表达的减少与银屑病斑块的临床改善显著正相关(P=0.002)。治疗后 Cx26 的免疫染色减少。
缝隙连接蛋白 Cx26 的表达改变可能在银屑病表型的发展中起作用。甲氨蝶呤和 PUVA 均显著降低 Cx26 mRNA 和蛋白的表达。