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, Reperfusion Injury, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
In Press
04 Aug 2022 : Original article
Long-Term Patency of All-in-One Sleeve Patch Graft Venoplasty in 16 Patients Who Underwent Living Donor Liv...Ann Transplant In Press; DOI: 10.12659/AOT.936888
22 Jul 2022 : Original article
Diagnostic Role of Tumor Markers for Hepatocellular Carcinoma in Liver Transplantation Candidates: An Analy...Ann Transplant In Press; DOI: 10.12659/AOT.936937
22 Jul 2022 : Original article
Development of a Novel Model for Predicting Postoperative Short-Term Outcome in Patients with Hepatitis B-R...Ann Transplant In Press; DOI: 10.12659/AOT.936732
22 Jul 2022 : Original article
Leucine-Rich Alpha-2-Glycoprotein (LRG-1) as a Potential Kidney Injury Marker in Kidney Transplant RecipientsAnn Transplant In Press; DOI: 10.12659/AOT.936751
Most Viewed Current Articles
26 Jan 2022 : Review article
Recurrence of Hepatocellular Carcinoma After Liver Transplantation: Risk Factors and Predictive ModelsDOI :10.12659/AOT.934924
Ann Transplant 2022; 27:e934924
29 Dec 2021 : Original article
Efficacy and Safety of Tacrolimus-Based Maintenance Regimens in De Novo Kidney Transplant Recipients: A Sys...DOI :10.12659/AOT.933588
Ann Transplant 2021; 26:e933588
24 Jul 2020 : Review article
Kidney Transplantation in the Times of COVID-19 – A Literature ReviewDOI :10.12659/AOT.925755
Ann Transplant 2020; 25:e925755
15 Mar 2022 : Case report
Combined Liver, Pancreas-Duodenum, and Kidney Transplantation for Patients with Hepatitis B Cirrhosis, Urem...DOI :10.12659/AOT.935860
Ann Transplant 2022; 27:e935860