Oncotarget

Research Papers:

Adipose-derived mesenchymal stem cells employed exosomes to attenuate AKI-CKD transition through tubular epithelial cell dependent Sox9 activation

Fengming Zhu, Octavia L.S. Chong Lee Shin, Guangchang Pei, Zhizhi Hu, Juan Yang, Han Zhu, Meng Wang, Jingyi Mou, Jie Sun, Yuxi Wang, Qian Yang, Zhi Zhao, Huzi Xu, Hui Gao, Weiqi Yao, Xiao Luo, Wenhui Liao, Gang Xu, Rui Zeng and Ying Yao _

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Oncotarget. 2017; 8:70707-70726. https://doi.org/10.18632/oncotarget.19979

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Abstract

Fengming Zhu1, Octavia L. S. Chong Lee Shin1, Guangchang Pei1, Zhizhi Hu1, Juan Yang1, Han Zhu1, Meng Wang1, Jingyi Mou1, Jie Sun1, Yuxi Wang1, Qian Yang1, Zhi Zhao1, Huzi Xu1, Hui Gao2, Weiqi Yao3, Xiao Luo4, Wenhui Liao5, Gang Xu1, Rui Zeng1 and Ying Yao1

1Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China

2Department of Clinical Nutrition, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China

3Wuhan Institute of Biotechnology, Guanggu Biolake, Wuhan 430000, Hubei, China

4Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China

5Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China

Correspondence to:

Ying Yao, email: [email protected]

Rui Zeng, email: [email protected]

Keywords: adipose-derived mesenchymal stem cells, exosomes, Sox9, AKI-CKD, tubular epithelial cells

Received: February 08, 2017    Accepted: July 18, 2017    Published: August 07, 2017

ABSTRACT

Acute kidney injury (AKI) predisposes patients to an increased risk into progressive chronic kidney disease (CKD), however effective treatments are still elusive. 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, a vital transcription factor in the development of kidney, in this process. C57BL/6 mice were subjected to unilateral renal ischemia/reperfusion (I/R) with or without hAD-MSC treatment. We found that hAD-MSC treatment upregulated the expression of 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. Similarly, Sox9 inhibitors reversed these protective effects. 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. Inhibiting the release of exosomes from hAD-MSCs or the expression of Sox9 in TECs reversed these antifibrotic effects. In conclusion, hAD-MSCs employed exosomes to mitigate AKI-CKD transition through tubular epithelial cell dependent activation of Sox9.


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