Project title
DPP4 抑制劑和GM-CSF 協同作用可藉由影響血管內皮前驅幹細胞改善急性腎損傷後腎臟的預後
Internal ID
NSC102-2314-B002-140-MY2
Principal Investigator
Start Date
August 1, 2014
End Date
July 12, 2015
Investigators
Organizations
Partner Organizations
Project Web Site
Corporate Action between CD26/DPP-IV Inhibition and GM-CSF Improves Kidney Function after Acute Kidney Injury---The Role of Endothelial Progenitor Cell = DPP4 抑制劑和GM-CSF 協同作用可藉由影響血管內皮前驅幹細胞改善急性腎損傷後腎臟的預後
Keywords
INDEX WORDS: Acute renal failure
DPP-IV Inhibition
GM-CSF
endothelial progenitor
cell
cell
Description
Acute kidney injury (AKI) is a serious complication, leading to prolonged hospitalization and patient mortality. When kidney suffer acute injury, vascular endothelial damage can not be recovered fully, result in renal dysfunction, impair renal microvascular endothelial injury, vascular remodeling and has a close correlation with the occurrence of chronic kidney disease. Previous study revealed that the endothelial cell layer could be damaged by the release of a variety of chemokines attract the endothelial progenitor cells released from bone marrow into blood and repair damaged sites of the vascular endothelial cell layer in order to maintain the functional integrity of endothelial progenitor cells was later confirmed in tissue hypoxia has a role in promoting angiogenesis. Dipeptidyl peptidase-4 (DPP-4) could digest lots of chemokines and colony-stimulating factor, such as stromal cell-derived factor (SDF-1) and affect the migration of stem cells. In vitro GM-CSF treatment up-regulates the peptidase DDP4, resulting in down-regulation of the functional ability of functional ability of the CD34+CD38- cells to response to the chemokine SDF-1, which could be overcome through the use of DPP4 inhibitors. However, through the addition of DPP4 inhibitors, it is possible to slow down the degradation of SDF-1, improve the homing ability, such as endothelial progenitor cells which carry the receptor of SDF-1: CXCR4. Our study will attempt to explore under the mode of acute kidney injury: (1) SDF-1 concentrations in the blood of patients with clinical acute kidney injury and endothelial progenitor cell number related. (2) In vitro study, the addition of GM-CSF and DPP4 inhibitors pretreated with endothelial progenitor cells, respectively, in order to regulate intracellular SDF-1/CXCR4 path activated endothelial progenitor cells, angiogenesis and the ability to move. (3) GM-CSF DPP4 inhibitors collaborative administration, to enhance endothelial progenitor cell homing and differentiation to damage the ability of the kidneys parts, mouse kidney after ischemia-reperfusion by SDF-1/CXCR4 path to improve vascular repair . We will use the Tie2-GFP bone marrow transplantation mice to track the homing of endothelial progenitor cells in the case of impaired renal vessels moving SDF-1/CXCR4 signal verification acute kidney injury after endothelial progenitor cells, accompanied by SDF-1 kidney conditional knockout mice ability nest normalized.