Abstract: TH-PO330
Adipose-Derived Mesenchymal Stem Cells Employed Exosomes to Attenuate AKI-CKD Transition through Tubular Epithelial Cell Dependent Sox9 Activation
Session Information
- AKI: Repair and Regeneration
November 02, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Acute Kidney Injury
- 002 AKI: Repair and Regeneration
Authors
- Zeng, Rui, Tongji Hospital, Wuhan, HuBei , China
- Yao, Ying, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Zhu, Fengming, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Background
Acute kidney injury (AKI) predisposes patients to an increased risk into progressive chronic kidney disease (CKD). Mesenchymal stem cells (MSCs) have been shown to promote recovery of injured tubular epithelial cells (TECs) in many kidney diseases. The transcription factor Sox9 is critical for renal development and has been reported to be activated within TECs upon renal injury. However, all these studies focused solely on AKI, whether MSCs can prevent AKI-CKD transition and what is the relationship of Sox9 activation to this process are largely unknown. This study aimed to investigate the therapeutic efficacy of human adipose-derived MSCs (hAD-MSCs) in the prevention of AKI-CKD transition, and illuminate the role of Sox9 in this process.
Methods
1. C57BL/6 mice were subjected to unilateral renal ischemia/reperfusion (I/R) with or without hAD-MSC treatment.
2. Exosomes derived from hAD-MSCs were extracted and injected into I/R mice through tail vein.
3. GW4869 was used to inhibit the release of exosomes.
4. The changes of kidney pathology, infiltration of inflammatory cells, hallmarks of kidney injury and repair were detected.
5. The activation of tubular Sox9 was assessed.
Results
We found that hAD-MSC treatment activated tubular Sox9, promoted tubular regeneration, attenuated AKI, and mitigated subsequent renal fibrosis. However, these beneficial effects were abolished by a drug inhibiting the release of exosomes from hAD-MSCs. Further, we verified that hAD-MSCs activated tubular Sox9 and prevented TGF-β1-induced transformation of TECs into pro-fibrotic phenotype through exosome shuttling in vitro, but the cells did not inhibit TGF-β1-induced transition of fibroblasts into myofibroblasts.
Conclusion
hAD-MSCs employed exosomes to mitigate AKI-CKD transition through tubular epithelial cell dependent activation of Sox9.
Funding
- Government Support - Non-U.S.