Abstract: SA-PO763
Putative Endothelial Progenitor Cells Protected Mice from Ischemia-Reperfusion-Induced Renal Fibrosis by Suppressing the Activation of PDGFR-β+ Pericytes via Paracrine Way
Session Information
- CKD: Mechanisms - III
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2103 CKD (Non-Dialysis): Mechanisms
Authors
- Wang, Meng, Tongji Hospital, Huazhong Univ of Science and Technology, Wuhan, HUBEI, China
- Yao, Ying, Tongji Hospital, Huazhong Univ of Science and Technology, Wuhan, HUBEI, China
- Zeng, Rui, Tongji Hospital, Huazhong Univ of Science and Technology, Wuhan, HUBEI, China
Background
Putative Endothelial progenitor cells (pEPCs) are defined as a group of stem cells which have the potential capacity to differentiate into endothelial cells. When tissues suffer from injury, they secrete factors to recruit pEPCs from bone marrow to injured site, involving in the vascular repair and protecting tissues from damage. However, the mechanism of pEPCs acting on ischemic organs, especially kidneys, is still not clear. Some studies showed that pEPCs participated in angiogenesis by directly intervening in vascular walls and differentiating into endothelial cells. Other studies claimed that pEPCs regulated long-distance targeting recipient cells via paracrine way. This study aimed to investigate the role and mechanism of pEPCs in ischemia reperfusion (IR)-induced renal fibrosis.
Methods
Mice were infused with pEPCs extracted from bone marrow of GFP mice 6 hours after IR surgery and sacrificed at day 5, 10 and 28. GFP+ pEPCs were tracked by immunofluorescence and flowcytometry. The pEPCs-cultured medium (pEPCs-CM) were infused to investigate the paracrine role of pEPCs. Platelet derived growth factor-BB (PDGF-BB), the ligand for platelet derived growth factor receptor-β (PDGFR-β), which is the specific surface receptor on pericytes, was adopted, in a selective pericyte knockout mice ( DTR expression in PDGFR-β+ cells), to detect the relationship between pEPCs and pericytes in the progression of IR-induced kidney disease.
Results
The results demonstrated that the adoptive transfer of pEPCs promoted the renal angiogenesis and attenuated renal fibrosis. Cell tracking experiments showed that few pEPCs were detected in IR kidney, suggesting the involvement of paracrine mechanism. We further found the injection of pEPCs-CM had an equal protective effect on kidney as pEPCs did. The transfer of pEPCs or pEPCs-CM inhibited IR-induced PDGFR-β expression, pericyte-endothelial detachment, pericyte proliferation and pericyte-myofibroblast transition. These protective effect of transferred pEPCs on capillary rarefaction and renal fibrosis was blocked by conditional PDGFR-β+ cell knockout.
Conclusion
The adoptive transfer of pEPCs ameliorated IR-induced capillary rarefaction and renal fibrosis by suppressing the activation of PDGFR-β+ pericytes via paracrine way.
Funding
- Government Support - Non-U.S.