Cross-talk between the dipeptidyl peptidase-4 and stromal cell-derived factor-1 in stem cell homing and myocardial repair: Potential impact of dipeptidyl peptidase-4 inhibitors

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• 作者：Marko Anderluh^a ; ^{marko.anderluh@ffa.uni-lj.si" class="auth_mail" title="E-mail the corresponding author} ; Gordana Kocic^b ; Katarina Tomovic^c ; Radivoj Kocic^d ; Marina Deljanin-Ilic^e ; Andrija Smelcerovic^c ; ^f
• 关键词：ACTH ; adrenocorticotrophic hormone (corticotropin) ; ADA ; adenosine deaminase ; CLIP ; corticotropin-like intermediary peptide ; CXCL12 ; CXC chemokine ligand 12 ; CXCR4 ; CXC chemokine receptor 4 ; DPP-2 ; DPP-8 and DPP-9 ; dipeptidyl peptidases-2 ; -8 and -9 ; DPP-4 ; dipeptidyl peptidase-4 ; GHRF ; growth hormone-releasing factor ; GIP ; glucose-dependent insulinotropic peptide (gastric inhibitory polypeptide) ; GLP-1 and GLP-2 ; glucagon-like peptides-1 and -2 ; GRP ; gastrin-releasing peptide ; hCGα ; human chori
• 刊名：Pharmacology and Therapeutics
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：167
• 期：Complete
• 页码：100-107
• 全文大小：1102 K

文摘

Dipeptidyl peptidase-4 (DPP-4), glycyl-prolyl-naphthylamidase, is a serine protease that catalyzes the hydrolysis of various proline-containing polypeptides. It is involved in the inactivation of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), having in this way a profound influence on glucose metabolism. During organ damage, stromal and endothelial cells produce a chemokine known as stromal cell-derived factor-1 (SDF-1), a powerful chemoattractant of stem/progenitor cells. SDF-1 binds to a specific α-chemokine receptor (CXCR4) and can be degraded by proteases, including matrix DPP-4/CD26, presented in the circulation, or activated in injured tissues. DPP-4 inhibition has received considerable attention because of its significant therapeutic benefits in the regulation of insulin secretion and tissue insulin sensitivity, the regulation of tumor growth and metastasis, angiogenesis, tissue repair, especially after myocardial infarction, and regulation of endocrine function. Inhibition of circulating proteases appears to maintain the optimal endogenous SDF-1 concentration and may enhance homing of endothelial progenitor cells. In the present article, we present an overview of some basic facts about the role of DPP-4 in glucose homeostasis, the mechanism of its inhibition, and a brief summary of available DPP-4 inhibitors. Furthermore, since protection against the overactivity of proteases is important for restorating cardiac function and repair after myocardial damage, necrosis and apoptosis, we propose that administration of a DPP-4 inhibitor may also be beneficial following myocardial infarction by the prevention of cleavage of stem cell chemoattractant cytokine SDF-1.