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细胞穿透性血红素加氧酶-1在小鼠特应性皮炎治疗中的应用

Cell-penetrating heme oxygenase-1 in the therapy of atopic dermatitis in mice.

作者信息

Tang Fang, Ma Xueqing, Sun Jiayu, Ru Minghui, Qian Tiansheng, Ji Wengjing, Qian Sifan, Li Hua

机构信息

School of Medicine, Huzhou University, Huzhou, Zhejiang 313000, P.R. China.

出版信息

Exp Ther Med. 2021 Sep;22(3):941. doi: 10.3892/etm.2021.10373. Epub 2021 Jul 1.

DOI:10.3892/etm.2021.10373
PMID:34306205
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8281355/
Abstract

Atopic dermatitis (AD), also referred to as atopic eczema, is a long-term inflammatory condition that is characterized by itchy, red, swollen and cracked skin. Accumulating evidence suggests that AD is caused by genetic factors, environmental exposure and immune system dysfunction; however, its underlying molecular mechanism remains unclear. Current treatment strategies aim to decrease the severity and frequency of flares. Heme oxygenase-1 (HO-1) is a nuclear factor erythroid 2-related factor 2 (Nrf2)-regulated gene that plays crucial roles against stress, inflammation and oxidation, and exerts cytoprotective effects. Previous studies have reported that treatment of AD induces high expression levels of HO-1 and Nrf2, indicating that HO-1 may play an important role in the treatment of AD. The present study constructed the recombinant protein, cell-penetrating peptide-HO-1 (CPP-HO-1), which was expressed in and isolated with a 6xHis-tag using HiTrap His column (1 ml). AD was established using 4-dinitrochlorobenzene (DNCB) in mice. It was observed that the CPP-HO-1 fusion protein decreased the severity of AD, inhibited scratching in mice and decreased skin inflammation. Taken together, the results of the present study suggested that the CPP-HO-1 fusion protein may play a protective role against DNCB-induced AD in mice.

摘要

特应性皮炎(AD),也被称为特应性湿疹,是一种长期的炎症性疾病,其特征为皮肤瘙痒、发红、肿胀和皲裂。越来越多的证据表明,AD是由遗传因素、环境暴露和免疫系统功能障碍引起的;然而,其潜在的分子机制仍不清楚。目前的治疗策略旨在降低皮疹发作的严重程度和频率。血红素加氧酶-1(HO-1)是一种由核因子红细胞2相关因子2(Nrf2)调控的基因,在抵抗应激、炎症和氧化方面发挥关键作用,并具有细胞保护作用。先前的研究报道,AD治疗可诱导HO-1和Nrf2的高表达水平,表明HO-1可能在AD治疗中发挥重要作用。本研究构建了重组蛋白,即细胞穿透肽-HO-1(CPP-HO-1),其在大肠杆菌中表达,并使用HiTrap His柱(1 ml)通过6xHis标签进行分离。使用二硝基氯苯(DNCB)在小鼠中建立AD模型。观察到CPP-HO-1融合蛋白降低了AD的严重程度,抑制了小鼠的搔抓行为,并减轻了皮肤炎症。综上所述,本研究结果表明,CPP-HO-1融合蛋白可能对DNCB诱导的小鼠AD起到保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a13/8281355/8929e62a9f7c/etm-22-03-10373-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a13/8281355/c73d2f218491/etm-22-03-10373-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a13/8281355/72f2b3355ec0/etm-22-03-10373-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a13/8281355/1176611023d4/etm-22-03-10373-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a13/8281355/8929e62a9f7c/etm-22-03-10373-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a13/8281355/c73d2f218491/etm-22-03-10373-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a13/8281355/72f2b3355ec0/etm-22-03-10373-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a13/8281355/1176611023d4/etm-22-03-10373-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a13/8281355/8929e62a9f7c/etm-22-03-10373-g03.jpg

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