Abstract: SA-PO440
The Extracellular Vesicles from Adipose Tissue-Derived Mesenchymal Stem Cells Attenuate the Renal Senescence via SP1/Klotho Pathway in Obesity
Session Information
- Development and Regenerative Medicine
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Development, Stem Cells, and Regenerative Medicine
- 500 Development, Stem Cells, and Regenerative Medicine
Authors
- Meng, Yu, First Affiliated Hospital, Jinan University, Guangzhou, China, Guangzhou, China
- Cui, Shuang, First Affiliated Hospital, Jinan University, Guangzhou, China, Guangzhou, China
- Liu, Huanhuan, First Affiliated Hospital, Jinan University, Guangzhou, China, Guangzhou, China
Background
Patients with obesity have a high risk of chronic renal disease and premature aging of the kidney has been proved as a major contributor. The extracellular vesicles from adipose tissue-derived mesenchymal stem cells (ADSCs-EVs) have therapeutic potential in many diseases. We aimed to investigate whether ADSCs-EVs could rejuvenate the senescent renal tubular cells in Obesity
Methods
ADSCs-EVs were isolated from the subcutaneous adipose tissues from healthy volunteers (n=6). The murine model with obesity was obtained after 8 weeks of the obese diet. ADSCs-EVs were injected to the obese mice in vivo and co-cultured with primary renal tubular cells from the obese mice in vitro. The level of senescence was assessed as P16, P21 with histological analysis and western blot. Next-generation mRNA sequencing (RNAseq) was performed to predict the key transcription factor. The expression of SP1 and Klotho were analyzed by PCR in cells .
Results
ADSCs-EVs treatment could rescue the obesity-induced senescence of renal tubular cells in vivo and in vitro. The expression of Klotho restored and the P16 was significantly ameliorated. Further study revealed the levels of SP1 and the Klotho were synergistically elevated after ADSCs-EVs treatment (Figure). RNA-seq identified five aging-associated genes upregulated after EVs treatment (fold change >2, p<0.05). The pathway analysis showed TGF- ß or ERK pathway could play a crucial role in ADSCs-EVs mediated rejuvenation through up-regulating transcription factor SP1 (Figure).
Conclusion
ADSCs-EVs ameliorate obesity-induced renal tubular injury by activating SP1 /Klotho and rescue senescence, thereby prevent the renal premature aging in obesity. ADSCs-EVs might be a natural nano-biomaterial for senescence-related diseases therapy.
Funding
- Government Support - Non-U.S.