07 March 2017 : Original article
Profiling Proteinic Changes Induced by Vildagliptin Treatment in a Mouse Lung Transplantation Model: The Role of Kininogen-1
Zheng Tang1ABCE, Wei Zhai2ABD, Zhiwei Wang1G*, Zhipeng Hu1BCF, Min Zhang1EFDOI: 10.12659/AOT.902002
Ann Transplant 2017; 22:128-137
Abstract
BACKGROUND: This study investigated the protective effects of pharmaceutical CD26/dipeptidylpeptidase-4 (CD26/DPP-4) inhibitor in lung transplantation (LTx). Changes in protein expression associated with the treatment were screened and identified to evaluate the role of kininogen-1 in early-term ischemia/reperfusion (I/R) injury after LTx.
MATERIAL AND METHODS: Orthotopic single LTx was performed in syngeneic C57BL/6 mice, with a pharmaceutical CD26/DPP-4 inhibitor (vildagliptin, subcutaneous injection, 10 mg/kg, every 12 h) administered to the investigational group. All donors were perfused and preserved with low potassium dextran (LPD). Grafts were harvested at 60 h post-transplantation after 8 h of cold ischemia. Myeloperoxidase activity and wet/dry weight ratio were measured, followed by histopathological examination. Proteins were separated, analyzed, and identified using proteomics and database searches. The target proteins were validated by Western blot. Immunohistochemical studies were performed in the same lung specimen locus.
RESULTS: Investigational group (IN) versus control group (CON) comparison showed decreased myeloperoxidase enzymatic activity, as well as decreased edema and interstitial-alveolar inflammation. Proteomics results revealed 78 spots with significant differences in abundance between the 2 groups. Fifteen proteins were identified. Kininogen-1 was up-regulated in CON and down-regulated in IN, with contrasting results for the heat shock protein 70. Immunohistochemical results revealed significantly different staining with kininogen-1 in alveolar macrophages and inflammatory cells.
CONCLUSIONS: Combined vildagliptin and LPD significantly ameliorated I/R injury after LTx. This treatment may change local pulmonary protein levels. Moreover, proper application of proteins such as kininogen-1 may enhance the protective effects against I/R injury during transplantation.
Keywords: Dipeptidyl Peptidase 4, Lung Transplantation, Proteomics, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
In Press
Original article
Steroid Use in ABO-Incompatible Kidney Transplants: Withdrawal vs MaintenanceAnn Transplant In Press; DOI: 10.12659/AOT.947747
Original article
Intra-Arterial Contrast-Enhanced Ultrasound for Transcatheter Thrombolysis in Post-Transplant Hepatic Arter...Ann Transplant In Press; DOI: 10.12659/AOT.947500
Original article
Early Atropine Protocol Enhances Dobutamine Stress Echocardiography in End-Stage Liver Disease: A Practical...Ann Transplant In Press; DOI: 10.12659/AOT.950166
Most Viewed Current Articles
15 Aug 2023 : Review article 7,358
Free-Circulating Nucleic Acids as Biomarkers in Patients After Solid Organ TransplantationDOI :10.12659/AOT.939750
Ann Transplant 2023; 28:e939750
03 Jan 2023 : Original article 7,222
Impact of Autologous Stem Cell Transplantation on Primary Central Nervous System Lymphoma in First-Line and...DOI :10.12659/AOT.938467
Ann Transplant 2023; 28:e938467
16 May 2023 : Original article 7,051
Breaking Antimicrobial Resistance: High-Dose Amoxicillin with Clavulanic Acid for Urinary Tract Infections ...DOI :10.12659/AOT.939258
Ann Transplant 2023; 28:e939258
28 May 2024 : Original article 6,655
Effect of Dexmedetomidine Combined with Remifentanil on Emergence Agitation During Awakening from Sevoflura...DOI :10.12659/AOT.943281
Ann Transplant 2024; 29:e943281