狗皮肤乳头状瘤中有机阳离子转运体 OCT3 的表达特征。

IF 1.9 3区 农林科学 Q3 DERMATOLOGY Veterinary dermatology Pub Date : 2024-10-02 DOI:10.1111/vde.13302
Berenice Liyare Sanz Ressel, Gimena Gomez Castro, Eduardo Carlos Mórtola, Adriana Raquel Massone, Claudio Gustavo Barbeito
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引用次数: 0

摘要

背景:哺乳动物雷帕霉素靶标(mTOR)信号通路的激活被认为是犬皮肤乳头状瘤(CPs)的一个常见分子事件,这为探索新型分子靶向疗法提供了合理的基础。最近的证据表明,二甲双胍可通过抑制 mTOR 信号通路来缩小小鼠 CPs 的大小。这些作用需要有机阳离子转运体 3(OCT3/SLC22A3)的表达,这是一种众所周知的二甲双胍摄取转运体:本研究旨在描述二甲双胍吸收转运体 OCT3 在显示出 mTOR 信号通路激活的犬 CP 样品中的表达模式,以预测这种增生性表皮病变是否可能对二甲双胍敏感:方法:通过免疫组化方法对先前构建的包含28个犬CP样本的组织芯片切片中OCT3的表达进行评估,并与先前评估的mTOR激活标记物pS6的表达进行比较:结果:在所有犬 CP 样本中,OCT3 在基底层和上基底层表皮细胞的膜和细胞质中均有高表达。结论和临床意义:这些结果表明,犬 CP 表现出对二甲双胍敏感的替代标记物表达,如上调的 OCT3 和 pS6 表达。综上所述,这些研究结果为早期评估二甲双胍的使用提供了依据,二甲双胍是一种基于机制的治疗方法,可用于治疗犬持续性或多发性 CPs 患者。
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Characterising the expression of the organic cation transporter OCT3 in cutaneous papillomas of dogs.

Background: The identification of the activation of the mammalian target of rapamycin (mTOR) signalling pathway as a frequent molecular event in canine cutaneous papillomas (CPs) has provided the rational foundation to explore novel molecular-targeted therapies. Recent evidence indicates that metformin reduces the size of CPs in mice by inhibiting the mTOR signalling pathway. These effects require the expression of the organic cation transporter 3 (OCT3/SLC22A3), a well-known metformin uptake transporter.

Hypothesis/objectives: The aim of the present study was to characterise the expression pattern of the metformin uptake transporter OCT3 in canine samples of CP that have shown activation of the mTOR signalling pathway in order to predict if this hyperplastic epidermal lesion is potentially sensitive to metformin.

Methods: The expression of OCT3 was evaluated by immunohistochemical investigation in sections of a previously constructed tissue microarray containing 28 samples of canine CP and compared with that previously evaluated for the mTOR activation marker pS6.

Results: OCT3 was highly expressed in the membrane and cytoplasm of the basal and suprabasal epidermal cells in all samples of canine CP. This OCT3 expression was localised at similar epidermal compartments to those observed for pS6.

Conclusions and clinical relevance: These results show that canine CPs exhibit the expression of surrogate markers that suggest sensitivity to metformin, such as upregulated OCT3 and pS6 expression. Taken together, these findings provide the rationale for the early assessment of the use of metformin as a mechanism-based therapeutic approach for treating canine patients with persistent or multiple CPs.

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来源期刊
Veterinary dermatology
Veterinary dermatology 农林科学-兽医学
CiteScore
3.20
自引率
21.40%
发文量
92
审稿时长
12-24 weeks
期刊介绍: Veterinary Dermatology is a bi-monthly, peer-reviewed, international journal which publishes papers on all aspects of the skin of mammals, birds, reptiles, amphibians and fish. Scientific research papers, clinical case reports and reviews covering the following aspects of dermatology will be considered for publication: -Skin structure (anatomy, histology, ultrastructure) -Skin function (physiology, biochemistry, pharmacology, immunology, genetics) -Skin microbiology and parasitology -Dermatopathology -Pathogenesis, diagnosis and treatment of skin diseases -New disease entities
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