Beckers Paul A J, Gielis Jan F, Van Schil Paul E, Adriaensen Dirk
Antwerp Surgical Training, Anatomy & Research Center, Department of Medicine, University of Antwerp, Wilrijk, Belgium.
Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, University of Antwerp, Wilrijk, Belgium.
Ann Transl Med. 2017 Mar;5(6):129. doi: 10.21037/atm.2017.01.41.
Dipeptidyl peptidase 4 (DPP4) is a cell surface protease that has been reported to play a role in glucose homeostasis, cancer, HIV, autoimmunity, immunology and inflammation. A role for DPP4 in ischemia-reperfusion injury (IRI) in the heart has been established. Dipeptidyl peptidase 4 inhibition (DPP4i) appeared to decrease infarct size, improves cardiac function and promotes myocardial regeneration. Lung ischemia reperfusion injury is caused by a complex mechanism in which macrophages and neutrophils play an important role. Generation of reactive oxygen species (ROS), uncoupling of nitric oxide synthase (NOS), activation of nuclear factor-κB (NF-κB), activation of nicotinamide adenine dinucleotide phosphate metabolism, and generation of pro-inflammatory cytokines lead to acute lung injury (ALI). In this review we present the current knowledge on DPP4 as a target to treat IRI in the lung. We also provide evidence of the roles of the DPP4 substrates glucagon-like peptide 1 (GLP-1), vasoactive intestinal peptide (VIP) and stromal cell-derived factor-1α (SDF-1α) in protection against oxidative stress through activation of the mitogen-activated protein kinase (MAPK) 1/2 and phosphatidylinositol 3'-kinase (PI3K)/Akt signal transduction pathways.
二肽基肽酶4（DPP4）是一种细胞表面蛋白酶，据报道其在葡萄糖稳态、癌症、艾滋病、自身免疫、免疫学和炎症中发挥作用。DPP4在心脏缺血再灌注损伤（IRI）中的作用已得到证实。二肽基肽酶4抑制（DPP4i）似乎可减小梗死面积、改善心脏功能并促进心肌再生。肺缺血再灌注损伤是由一种复杂机制引起的，其中巨噬细胞和中性粒细胞起重要作用。活性氧（ROS）的产生、一氧化氮合酶（NOS）的解偶联、核因子-κB（NF-κB）的激活、烟酰胺腺嘌呤二核苷酸磷酸代谢的激活以及促炎细胞因子的产生会导致急性肺损伤（ALI）。在本综述中，我们介绍了目前关于DPP4作为治疗肺部IRI靶点的知识。我们还提供了DPP4底物胰高血糖素样肽1（GLP-1）、血管活性肠肽（VIP）和基质细胞衍生因子-1α（SDF-1α）通过激活丝裂原活化蛋白激酶（MAPK）1/2和磷脂酰肌醇3'-激酶（PI3K）/Akt信号转导途径来抵抗氧化应激作用的证据。
