scholarly journals DPP4 inhibition: Preventing SARS‐CoV ‐2 infection and/or progression of COVID ‐19?

2020 ◽  
Vol 36 (8) ◽  
Author(s):  
Rocky Strollo ◽  
Paolo Pozzilli
Keyword(s):  
Dpp4 Inhibition

scholarly journals MA04.10 Lung Cancer Growth is Suppressed by CD26/DPP4-Inhibition via Enhanced NK Cell and Macrophage Recruitment

2017 ◽  
Vol 12 (1) ◽  
pp. S362-S363 ◽  
Author(s):  
Jae-Hwi Jang ◽  
Florian Janker ◽  
Stephan Arni ◽  
Yoshito Yamada ◽  
Walter Weder ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Nk Cell ◽  
Cancer Growth ◽  
Macrophage Recruitment ◽  
Dpp4 Inhibition

scholarly journals DPP4 Inhibition Ameliorates Cardiac Function by Blocking the Cleavage of HMGB1 in Diabetic Mice After Myocardial Infarction

2017 ◽  
Vol 58 (5) ◽  
pp. 778-786 ◽  
Author(s):  
Akihiko Sato ◽  
Satoshi Suzuki ◽  
Shunsuke Watanabe ◽  
Takeshi Shimizu ◽  
Yuichi Nakamura ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Diabetic Mice ◽  
Dpp4 Inhibition

scholarly journals Chromatin and transcriptome changes in human myoblasts show spatio-temporal correlations and demonstrate DPP4 inhibition in differentiated myotubes

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Tomasz J. Kolanowski ◽  
Natalia Rozwadowska ◽  
Agnieszka Zimna ◽  
Magdalena Nowaczyk ◽  
Marcin Siatkowski ◽  
...  
Keyword(s):  
Temporal Correlations ◽  
Spatio Temporal ◽  
Dpp4 Inhibition

scholarly journals Functional Roles for CD26/DPP4 in Mediating Inflammatory Responses of Pulmonary Vascular Endothelial Cells

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3508
Author(s):  
Yukiko Takahashi ◽  
Takeshi Kawasaki ◽  
Hironori Sato ◽  
Yoshinori Hasegawa ◽  
Steven M. Dudek ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Lung Injury ◽  
Barrier Function ◽  
Inflammatory Responses ◽  
Transmembrane Protein ◽  
Quantitative Polymerase Chain Reaction ◽  
Enzyme Linked Immunosorbent Assay ◽  
Regenerative Processes ◽  
Dpp4 Inhibition

Excessive inflammation in the lung is a primary cause of acute respiratory distress syndrome (ARDS). CD26/dipeptidyl peptidase-4 (DPP4) is a transmembrane protein that is expressed in various cell types and exerts multiple pleiotropic effects. We recently reported that pharmacological CD26/DPP4 inhibition ameliorated lipopolysaccharide (LPS)-induced lung injury in mice and exerted anti-inflammatory effects on human lung microvascular endothelial cells (HLMVECs), in vitro. However, the mechanistic roles of CD26/DPP4 in lung injury and its effects on HLMVECs remain unclear. In this study, transcriptome analysis, followed by various confirmation experiments using siRNA in cultured HLMVECs, are performed to evaluate the role of CD26/DPP4 in response to the pro-inflammatory involved in inflammation, barrier function, and regenerative processes in HLMVECs after pro-inflammatory stimulation. These are all functions that are closely related to the pathophysiology and repair process of lung injury. Confirmatory experiments using flow cytometry; enzyme-linked immunosorbent assay; quantitative polymerase chain reaction; dextran permeability assay; WST-8 assay; wound healing assay; and tube formation assay, reveal that the reduction of CD26/DPP4 via siRNA is associated with altered parameters of inflammation, barrier function, and the regenerative processes in HLMVECs. Thus, CD26/DPP4 can play a pathological role in mediating injury in pulmonary endothelial cells. CD26/DPP4 inhibition can be a new therapeutic strategy for inflammatory lung diseases, involving pulmonary vascular damage.

scholarly journals SARS-CoV-2 and DPP4 inhibition: Is it time to pray for Janus Bifrons?

2020 ◽  
Vol 163 ◽  
pp. 108162 ◽  
Author(s):  
Dario Pitocco ◽  
Linda Tartaglione ◽  
Luca Viti ◽  
Mauro Di Leo ◽  
Alfredo Pontecorvi ◽  
...  
Keyword(s):  
Dpp4 Inhibition

scholarly journals New Molecular Insights into the Inhibition of Dipeptidyl Peptidase-4 by Natural Cyclic Peptide Oxytocin

Molecules ◽  
2019 ◽  
Vol 24 (21) ◽  
pp. 3887
Author(s):  
Veera C. S. R. Chittepu ◽  
Poonam Kalhotra ◽  
Tzayhri Osorio-Gallardo ◽  
Cristian Jiménez-Martínez ◽  
Raúl René Robles-de la Torre ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Serine Protease ◽  
Cyclic Peptides ◽  
Cyclic Peptide ◽  
Dipeptidyl Peptidase ◽  
Dependent Manner ◽  
Protease Inhibition ◽  
Dipeptidyl Peptidase 4 ◽  
Glucose Levels ◽  
Dpp4 Inhibition

Protease inhibition has led to treating many diseases and has been successful in producing many commercial drugs by pharmaceutical companies. Among many proteases, serine protease has been attractive in treating metabolic disorder diabetes mellitus (DM). Gliptins have been proven to inhibit dipeptidyl peptidase-4 (DPP4), a serine protease, and are an emerging therapeutic drug target to reduce blood glucose levels, but until now there is no natural cyclic peptide proven to inhibit serine protease DPP4. This study demonstrates the potential mechanism of natural cyclic peptide oxytocin (OXT) as a DPP4 inhibitor. To achieve this, initially, activity atlas and field-based models of DPP4 inhibitors were utilized to predict the possible features of positive and negative electrostatic, hydrophobic, and activity shapes of DPP4 inhibition. Oxytocin binding mode, flexibility, and interacting residues were studied using molecular docking simulations studies. 3D-RISM calculations studies revealed that the stability of water molecules at the binding site are favorable. Finally, an experimental study using fluorescence assay revealed OXT inhibits DPP4 in a concentration-dependent manner in a significant way (p < 0.05) and possess IC50 of 110.7 nM. These new findings significantly expand the pharmaceutical application of cyclic peptides, and in specific OXT, and implicate further optimization of OXT inhibition capacity to understand the effect of DPP4 inhibition. This work highlights the development of natural cyclic peptides as future therapeutic peptides to reduce glucose levels and treat diabetes mellitus.

scholarly journals DPP4 inhibition by sitagliptin attenuates LPS-induced lung injury in mice

2018 ◽  
Vol 315 (5) ◽  
pp. L834-L845 ◽  
Author(s):  
Takeshi Kawasaki ◽  
Weiguo Chen ◽  
Yu Maw Htwe ◽  
Koichiro Tatsumi ◽  
Steven M. Dudek
Keyword(s):  
Epithelial Cells ◽  
Lung Injury ◽  
Human Lung ◽  
Cell Number ◽  
Lung Epithelial Cells ◽  
Dpp4 Inhibitors ◽  
Anti Inflammatory ◽  
Dpp4 Inhibition

Acute respiratory distress syndrome (ARDS) is a severe clinical condition marked by acute respiratory failure and dysregulated inflammation. Pulmonary vascular endothelial cells (PVECs) function as an important pro-inflammatory source in ARDS, suggesting that modulation of inflammatory events at the endothelial level may have a therapeutic benefit. Dipeptidyl peptidase-4 (DPP4) inhibitors, widely used for the treatment of diabetes mellitus, have been reported to have possible anti-inflammatory effects. However, the potential anti-inflammatory effects of DPP4 inhibition on PVEC function and ARDS pathophysiology are unknown. Therefore, we evaluated the effects of sitagliptin, a DPP4 inhibitor in wide clinical use, on LPS-induced lung injury in mice and in human lung ECs in vitro. In vivo, sitagliptin reduced serum DPP4 activity, bronchoalveolar lavage protein concentration, cell number, and proinflammatory cytokine levels after LPS and alleviated histological findings of lung injury. LPS decreased the expression levels of CD26/DPP4 on pulmonary epithelial cells and PVECs isolated from mouse lungs, and the effect was partially reversed by sitagliptin. In vitro, human lung microvascular ECs (HLMVECs) expressed higher levels of CD26/DPP4 than human pulmonary arterial ECs. LPS induced the release of TNFα, IL-6, and IL-8 by HLMVECs that were inhibited by sitagliptin. LPS promoted the proliferation of HLMVECs, and sitagliptin suppressed this response. However, sitagliptin failed to reverse LPS-induced permeability in cultured ECs or lung epithelial cells in vitro. In summary, sitagliptin attenuates LPS-induced lung injury in mice and exerts anti-inflammatory effects on HLMVECs. These novel observations indicate DPP4 inhibitors may have potential as therapeutic drugs for ARDS.

DPP4 inhibition improves functional outcome after renal ischemia-reperfusion injury

2012 ◽  
Vol 303 (5) ◽  
pp. F681-F688 ◽  
Author(s):  
Lorenzo L. F. Glorie ◽  
Anja Verhulst ◽  
Veerle Matheeussen ◽  
Lesley Baerts ◽  
Joanna Magielse ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Mrna Expression ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Renal Ischemia ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Protective Effects ◽  
Dipeptidyl Peptidase 4 ◽  
Dpp4 Inhibition

Dipeptidyl peptidase 4 (DPP4) is an exopeptidase which modulates the function of its substrates, among which are insulin-releasing incretins. DPP4 inhibitors are currently used to improve glucose tolerance in type 2 diabetes patients. Inhibition of DPP4 exhibits protective effects on ischemia-reperfusion injury (IRI) of the heart and lung. As DPP4 and its substrates are also expressed in the kidney, we studied the effect of the DPP4 inhibitor vildagliptin on the outcome of IRI-induced acute kidney injury in rats in a model of 30-min unilateral renal ischemia, followed by contralateral nephrectomy. Saline, 1, or 10 mg/kg vildagliptin (VG1/VG10) was administered intravenously 15 min before the surgery. Animals were euthanized after 2, 12, amd 48 h of reperfusion. DPP4 inhibition resulted in a significant dose-dependent decrease in serum creatinine (1.31 ± 0.32 and 0.70 ± 0.19 mg/dl for VG1 and VG10, respectively, vs. 1.91 ± 0.28 mg/dl for controls at 12 h; P < 0.01). Tubular morphology (PAS-PCNA) revealed significantly reduced tubular necrosis at 12 h (62.1 ± 18.0 and 77.5 ± 22.0% in VG10 and saline, respectively). VG did not affect regeneration but decreased apoptosis, as shown by twofold decreased Bax/Bcl-2 mRNA expression and a threefold decrease in apoptotic bodies on terminal deoxynucleotidyl transferase dUTP nick-end labeling-stained sections. VG treatment significantly reduced serum malondialdehyde twofold in both VG1- and VG10-treated ischemic and sham-operated animals compared with controls and also resulted in a significant decrease in mRNA expression of the proinflammatory marker CXCL10 at 2 h of reperfusion. Through a mechanism yet to be fully understood, VG treatment results in a functional protection of the kidney against IRI. This protection was associated with antiapoptotic, immunological, and antioxidative changes.

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