Dipeptidyl peptidase-4（DPP-4）是一種細(xì)胞表面酶，也被稱為CD26。它是一種既有蛋白酶作用，又有調(diào)節(jié)功能的酶，主要參與胰高血糖素樣肽-1(GLP-1)和胰島素樣生長因子-1（IGF-1）等多種肽類激素的代謝。DPP-4廣泛分布于人體的多個組織和細(xì)胞中，包括胰島β細(xì)胞、消化道、肺部、免疫細(xì)胞、肝臟、腎臟等，其功能不僅限于調(diào)節(jié)代謝激素，還可能涉及到炎癥、免疫和癌癥等方面的生物學(xué)過程。目前，DPP-4在糖尿病、炎癥性疾病、癌癥等多種疾病中被廣泛研究。

Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC. Its binding to CAV1 and CARD11 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner. Its interaction with ADA also regulates lymphocyte-epithelial cell adhesion. In association with FAP is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM. May be involved in the promotion of lymphatic endothelial cells adhesion, migration and tube formation. When overexpressed, enhanced cell proliferation, a process inhibited by GPC3. Acts also as a serine exopeptidase with a dipeptidyl peptidase activity that regulates various physiological processes by cleaving peptides in the circulation, including many chemokines, mitogenic growth factors, neuropeptides and peptide hormones. Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline.

1. These data indicate that DPP-4 is modulated in a tissue specific manner and is dependent on physiological conditions such as hyperglycaemia and insulin resistance, suggesting a significant role in disorders such as diabetes. PMID: 29412816
2. DPP4 activity when compared to healthy controls. Analysis of Dpp4-Liv-Tg mice revealed elevated systemic DPP4 activity and diminished active GLP-1 levels. PMID: 29031724
3. hepatocyte DPP4 promotes visceral adipose tissue inflammation and insulin resistance in obesity, and targeting this pathway may have metabolic benefits that are distinct from those observed with oral DPP4 inhibitors PMID: 29562231
4. DPP-4 inhibition with linagliptin slowed the progression of premature aging in klotho-/- mice. Provide a novel insight into the potential role of DPP-4 in the mechanism of premature aging. PMID: 29195509
5. Chronic stress accelerates DPP4-mediated GLP-1 degradation and alters plasma adiponectin, accelerating vascular senescence and impairing ischemia-induced neovascularization. PMID: 28963101
6. p53 limits ferroptosis of colorectal cancer cells by blocking DPP4 activity. PMID: 28813679
7. DPP4 can regulate chronic stress-induced hematopoietic stemc cell activation and inflammatory cell production via an Adrbeta3/CXCL12-dependent mechanism that is mediated by the GLP-1/GLP-1R axis. PMID: 28710180
8. DPPIV-knockout mice showed attenuation of scratching in psoriatic pruritus disease model. PMID: 28365081
9. Actions of several substrate chemokines might be potentiated by downregulation of DPP-4, synergistically with upregulation of chemokines and their receptors in adipose tissues of obese mice. PMID: 28222464
10. Inhibition of DPP-4 activity by linagliptin reverses Western diet-induced diastolic dysfunction, possibly by targeting TRAF3IP2 expression and its downstream inflammatory signaling. PMID: 28476142
11. DPP4 is pro-fibrotic in Carbon tetrachloride-induced liver fibrosis. PMID: 27899813
12. systemic DPP4 inhibition restores the impaired mononuclear cell homing in Eng+/- animals post-myocardial infarction, and enhances cardiac repair, which might be explained by restoring the balance between the inflammatory and regenerative macrophages present in the heart PMID: 29253907
13. SGLT-2 inhibition with dapagliflozin reduces the activation of the Nlrp3/ASC inflammasome and attenuates the development of diabetic cardiomyopathy in mice with type 2 diabetes. Effects are augmentated of the by DPP4 inhibitor Saxagliptin. PMID: 28447181
14. DPP-4 inhibitor teneligliptin inhibited atherogenesis in ApoE knockout mice, at least partially, through attenuation of the inflammatory phenotype of perivascular adipose tissue. PMID: 28347868
15. Increased plasma DPP-4 activity may correlate with aneurysmal development. CD26 on monocytes plays a critical role in cell differentiation, possibly mediated by extracellular signal-regulated protein kinase 1/2-p21 axis signaling pathways and cytoskeletal proteins reassembly. PMID: 27887857
16. High DPP4 expression is associated with cardiac ischemia and systolic dysfunction. PMID: 28771625
17. these findings identify distinct roles for DPP4 in the endothelial cell versus the bone marrow compartment for selective incretin degradation and DPP4 inhibition-mediated glucoregulation. PMID: 27839908
18. The trimeric form receptor-binding domain of MERS-CoV spike protein bound strongly to the receptor of MERS-CoV, dipeptidyl peptidase 4 (DPP4), and elicited robust RBD-specific neutralizing antibodies in mice. PMID: 27750111
19. the data show that glucose-induced expression of Dpp4 in the liver is facilitated by demethylation of the Dpp4 gene early in life. This might contribute to early deteriorations in hepatic function, which in turn result in metabolic disease such as hepatosteatosis later in life. PMID: 27999105
20. study reveals a cross talk between ATR signaling and DPP4 activation in the regulation of megalin and underscores the significance of targeting DPP4 in the prevention of obesity related kidney injury progression. PMID: 27213360
21. Data (including data from studies in knockout mice) suggest that Cd26 (dipeptidyl peptidase IV) plays role in development and progression vs. resolution of ulcerative colitis; Cd26 deficiency in knockout mice is associated with heightened response to DSS (dextran sulfate sodium) in inducing colitis and is accompanied by increased expression of NF-kappaB p65 subunit and distinct changes in leukocyte trafficking/infiltra... PMID: 27125676
22. DPP4 posttranslational modification of selected chemokines by truncation modifies their functional activities. PMID: 26943017
23. DPP-4I, MK0626, but not native incretins has protective effects against AAA in Ang II-infused Apoe/ mice via suppression of inflammation, proteolysis, and fibrosis in the aortic wall PMID: 26549734
24. Plasminogen may regulate DPP-4 activity and glucose metabolism. PMID: 27592166
25. Data suggest that pharmacological stimulation of serotonin 5Ht1b receptor enhances up-regulation of plasma Glp1 (glucagon-like peptide 1) induced by Dpp4 (dipeptidylpeptidase 4) inhibition independently of feeding and also improves glucose tolerance. PMID: 26234524
26. Young euglycemic Dpp4 KO mice showed a cardioprotective response after transverse aortic constriction or doxorubicin administration, with reduced fibrosis; however, cardiac mRNA analysis revealed increased expression of inflammation-related transcripts. PMID: 26672095
27. Dipeptidyl peptidase-4 inhibition by gemigliptin exerts a preventative effect on the proliferation and migration of VSMCs via Nrf2. PMID: 26187356
28. The present study reveals the activation of autophagy to mediate the anti-diabetic effect of GLP-1. PMID: 26802468
29. These results indicate that DPP-4 inhibitors pleiotropically exert a direct renoprotective effect, and may serve as an additional therapeutic strategy to protect proximal tubular cells against proteinuria in patients with diabetic nephropathy. PMID: 26802469
30. DPP-4 and integrin beta1 interactions regulate key endothelial cell signal transduction in both physiological and pathological conditions including endothelial mesenchymal transformation. PMID: 25830763
31. sDPP-4 enhances inflammatory actions via TLR pathway, while DPP-4 inhibition with either an enzymatic or binding inhibitor has anti-inflammatory effects. PMID: 26773932
32. DPP4i restores cardiac remodeling and apoptosis caused by the pathological decline in circulating GLP-1 in response to pressure overload. EPAC1 is essential for cardiomyocyte survival via the cAMP/Rap1 activation independently of PKA. PMID: 26721911
33. Combination of DPP-4 inhibitor and PPARgamma agonist exerts protective effects on pancreatic beta-cells in diabetic db/db mice through the augmentation of IRS-2 expression PMID: 26116826
34. DPP4 inhibiton appeared to suppress neointimal formation by inhibiting inflammation, independently of its effects on glucose or cholesterol metabolism in atherogenic LDL receptor KO mice. PMID: 25770025
35. Report design, synthesis and activity of series of fused beta-homophenylalanine inhibitors of dipeptidyl peptidase-4. PMID: 25871012
36. dipeptidyl peptidase 4 activity was impaired in animals with aggressive disease relative to cancer-free littermates. PMID: 25056937
37. DPP4 inhibitors MK-0626 attenuates hepatic steatosis through enhancing AMPK activity, inhibiting hepatic lipogenic gene expression, enhancing triglyceride secretion from liver and increasing serum adiponectin levels. PMID: 25473177
38. islet DPP-4 is species-specifically expressed in alpha-cell and beta-cell dominant patterns in several species and both patterns remained robust in enzyme activity during short-term metabolic challenge. PMID: 25268763
39. Glycosylation of mouse DPP4 plays a role in inhibiting Middle East respiratory syndrome coronavirus infection. PMID: 25653445
40. CD26 inhibition increased macrophage number around growing collaterals. PMID: 23391419
41. These results indicate that DPPIV functions as a chemorepellent of human and mouse neutrophils PMID: 23677473
42. Results provide preclinical evidence of CD26, in the hematopoietic stem cell transplantation (HSCT) recipient, as a major regulator of hematopoietic stem and progenitor cell (HSC/HPC) engraftment with minor effects on HSC/HPC homing. PMID: 22882234
43. The nonenzymatic function of DPP4 on DC may play a role in potentiation of inflammation in obesity by interacting with adenosine deaminase. PMID: 22936179
44. in both mice and rats, peripheral GLP-1 reduces food intake significantly less than Ex-4, even when protected from DPP-4 PMID: 23033273
45. In the acute phase of colitis, colonic DPP IV activity is significantly decreased compared with healthy animals. PMID: 22125312
46. DPPIV and NPY interact on lipid metabolism to promote adipose tissue depot. PMID: 22819773
47. DPP-4 activity was inhibited by oral administration of linagliptin during healing. PMID: 22493041
48. the ability of DPP-4 inhibition to suppress the progression to STZ-induced hyperglycaemia involves both alleviation of beta cell death and alpha cell proliferation PMID: 22072158
49. dipeptidyl peptidase-4 inhibitor vildagliptin has an effect on glucose tolerance and beta-cell function and mass in insulin receptor substrate-2-knockout mice fed a high-fat diet PMID: 22315446
50. CD26 expression was increased in dermal fibroblasts following skin wounding but was downregulated in tumour stroma PMID: 21765471

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[Dipeptidyl peptidase 4 soluble form]: Secreted.; Cell membrane; Single-pass type II membrane protein. Apical cell membrane; Single-pass type II membrane protein. Cell projection, invadopodium membrane; Single-pass type II membrane protein. Cell projection, lamellipodium membrane; Single-pass type II membrane protein. Cell junction. Membrane raft.

Peptidase S9B family, DPPIV subfamily

KEGG: mmu:13482

STRING: 10090.ENSMUSP00000044050

UniGene: Mm.1151