Department of Thoracic Surgery, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Br J Pharmacol. 2023 Nov;180(22):2846-2861. doi: 10.1111/bph.15967. Epub 2022 Nov 1.
Cluster of differentiation 26 (CD26)/dipeptidyl peptidase 4 (DPP4) is an exopeptidase that is expressed as a transmembrane protein in many organs but also present in a circulating soluble form. Beyond its enzymatic and costimulatory activity, CD26/DPP4 is involved in the pathogenesis of chronic fibrotic diseases across many organ types, such as liver cirrhosis, kidney fibrosis and lung fibrosis. Organ fibrosis is associated with a high morbidity and mortality, and there are no causative therapies that can effectively attenuate the progress of the disease. Growing evidence suggests that inhibiting CD26/DPP4 can modulate the profibrotic tissue microenvironment and thus reduce fibrotic changes within affected organs. This review summarizes the role of CD26/DPP4 in fibroproliferative disorders and highlights new opportunities for an antifibrotic treatment by CD26/DPP4 inhibition. As a major advantage, CD26/DPP4 inhibitors have been in safe and routine clinical use in type 2 diabetes for many years and thus qualify for repurposing to repurpose as a promising therapeutic against fibrosis. LINKED ARTICLES: This article is part of a themed issue on Translational Advances in Fibrosis as a Therapeutic Target. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.22/issuetoc.
CD26/二肽基肽酶 4（DPP4）是一种外肽酶，以跨膜蛋白的形式在许多器官中表达，也以循环可溶性形式存在。除了其酶和共刺激活性外，CD26/DPP4 还参与多种器官类型的慢性纤维化疾病的发病机制，如肝硬化、肾纤维化和肺纤维化。器官纤维化与高发病率和死亡率相关，并且没有有效的病因治疗方法可以有效减缓疾病的进展。越来越多的证据表明，抑制 CD26/DPP4 可以调节促纤维化的组织微环境，从而减少受影响器官中的纤维化变化。这篇综述总结了 CD26/DPP4 在纤维增生性疾病中的作用，并强调了通过抑制 CD26/DPP4 进行抗纤维化治疗的新机会。作为一个主要优势，CD26/DPP4 抑制剂已在 2 型糖尿病的安全和常规临床应用多年，因此有资格重新用于治疗纤维化。相关文章：本文是关于纤维化作为治疗靶点的转化进展的专题的一部分。要查看本节中的其他文章，请访问 http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.22/issuetoc.
