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色氨酸代谢通过犬尿氨酸途径:在实体器官移植中的作用。

Tryptophan Metabolism via Kynurenine Pathway: Role in Solid Organ Transplantation.

机构信息

General, Visceral and Transplant Surgery, Department of Surgery, Medical University of Graz, Auenbruggerpl. 2, 8036 Graz, Austria.

Faculty of Medicine, Vilnius University, M. K. Ciurlionio 21, 03101 Vilnius, Lithuania.

出版信息

Int J Mol Sci. 2021 Feb 15;22(4):1921. doi: 10.3390/ijms22041921.

Abstract

Solid organ transplantation is a gold standard treatment for patients suffering from an end-stage organ disease. Patient and graft survival have vastly improved during the last couple of decades; however, the field of transplantation still encounters several unique challenges, such as a shortage of transplantable organs and increasing pool of extended criteria donor (ECD) organs, which are extremely prone to ischemia-reperfusion injury (IRI), risk of graft rejection and challenges in immune regulation. Moreover, accurate and specific biomarkers, which can timely predict allograft dysfunction and/or rejection, are lacking. The essential amino acid tryptophan and, especially, its metabolites via the kynurenine pathway has been widely studied as a contributor and a therapeutic target in various diseases, such as neuropsychiatric, autoimmune disorders, allergies, infections and malignancies. The tryptophan-kynurenine pathway has also gained interest in solid organ transplantation and a variety of experimental studies investigating its role both in IRI and immune regulation after allograft implantation was first published. In this review, the current evidence regarding the role of tryptophan and its metabolites in solid organ transplantation is presented, giving insights into molecular mechanisms and into therapeutic and diagnostic/prognostic possibilities.

摘要

实体器官移植是治疗终末期器官疾病患者的金标准治疗方法。在过去几十年中,患者和移植物的存活率有了很大的提高;然而,移植领域仍然面临着一些独特的挑战,如可移植器官的短缺和扩展标准供体(ECD)器官数量的增加,这些器官极易发生缺血再灌注损伤(IRI)、移植物排斥的风险和免疫调节的挑战。此外,缺乏能够及时预测同种异体移植功能障碍和/或排斥反应的准确和特异性生物标志物。必需氨基酸色氨酸及其通过犬尿氨酸途径的代谢物已被广泛研究为各种疾病(如神经精神疾病、自身免疫性疾病、过敏、感染和恶性肿瘤)的一个贡献者和治疗靶点。色氨酸-犬尿氨酸途径在实体器官移植中也引起了关注,并且首次发表了各种研究其在同种异体移植后 IRI 和免疫调节中的作用的实验研究。在这篇综述中,介绍了色氨酸及其代谢物在实体器官移植中的作用的现有证据,深入了解了分子机制以及治疗和诊断/预后的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea6c/7919278/667a815c8176/ijms-22-01921-g001.jpg

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