Changes in AmotL2 Expression in Cells of the Human Enteral Nervous System in Oxaliplatin-Induced Enteric Neuropathy

Rebeca Gonzalez-Fernandez,Rita Martin-Ramirez,Maria-del-Carmen Maeso,Alberto Lazaro,Julio Avila,Pablo Martin-Vasallo,Manuel Morales

Biomedicines（2024）

Hosp Univ Nuestra Senora Candelaria

Cited 0|Views3

Abstract

Gastrointestinal (GI) toxicity is a common side effect in patients undergoing oxaliplatin (OxPt)-based chemotherapy for colorectal cancer (CRC). Frequently, this complication persists in the long term and could affect the efficacy of the treatment and the patient’s life quality. This long-term GI toxicity is thought to be related to OxPt-induced enteral neuropathy. AmotL2 is a member of the Angiomotin family of proteins, which play a role in cell survival, neurite outgrowth, synaptic maturation, oxidative stress protection, and inflammation. In order to assess the role of AmotL2 in OxPt-induced enteral neuropathy, we studied the expression of AmotL2 in cells of the enteric nervous system (ENS) of untreated and OxPt-treated CRC patients and its relationship with inflammation, using immunofluorescence confocal microscopy. Our results in human samples show that the total number of neurons and glial cells decreased in OxPt-treated patients, and TNF-α and AmotL2 expression was increased and colocalized in both neurons and glia. AmotL2 differential expression between OxPt-treated and untreated CRC patients shows the involvement of this scaffold protein in the inflammatory component and toxicity by OxPt in the ENS.

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Key words

AmotL2,enteral nervous system,oxaliplatin toxicity,gastrointestinal chemotherapy toxicity,enteral nervous system toxicity

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【要点】：论文研究了AmotL2在奥沙利铂诱导的肠神经病变中的作用，发现AmotL2表达增加与神经元和胶质细胞炎症反应相关，揭示了其在肠神经病变中的重要性。

【方法】：通过免疫荧光共聚焦显微镜技术，比较了未治疗和奥沙利铂治疗的CRC患者肠神经系统细胞中AmotL2的表达。

【实验】：实验在人类样本上进行，观察到奥沙利铂治疗的患者中神经元和胶质细胞总数减少，TNF-α和AmotL2表达增加并在神经元和胶质细胞中共同定位，使用的数据集为CRC患者的肠神经系统细胞样本，结果显示AmotL2在奥沙利铂诱导的肠神经病变中起作用。