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  3. HucMSC exosomes attenuate partial bladder outlet obstruction-induced renal injury and cell proliferation via the Wnt/β-catenin pathway

HucMSC exosomes attenuate partial bladder outlet obstruction-induced renal injury and cell proliferation via the Wnt/β-catenin pathway

  • Eur J Pharmacol. 2023 Jan 31;175523. doi: 10.1016/j.ejphar.2023.175523.
Zhaoying Wang 1,  Yihang Yu 1,  Liming Jin 1,  Xiaojun Tan 1,  Bo Liu 2,  Zhaoxia Zhang 1,  Zhang Wang 1,  Chunlan Long 1,  Lianju Shen 1,  Guanghui Wei 3,  Dawei He 4
Affiliations

Affiliations

  • 1 Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing, 400014, PR China; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, 400014, PR China; National Clinical Research Center for Child Health and Disorders, Chongqing, 400014, PR China; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, 400014, PR China; Chongqing Key Laboratory of Pediatrics, Chongqing, 400014, PR China.
  • 2 Department of Cardiothoracic Surgery, Children's Hospital of Chongqing Medical University, Chongqing, 400014, PR China; Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing, 400014, PR China; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, 400014, PR China; National Clinical Research Center for Child Health and Disorders, Chongqing, 400014, PR China; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, 400014, PR China; Chongqing Key Laboratory of Pediatrics, Chongqing, 400014, PR China.
  • 3 Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, PR China; Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing, 400014, PR China; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, 400014, PR China; National Clinical Research Center for Child Health and Disorders, Chongqing, 400014, PR China; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, 400014, PR China; Chongqing Key Laboratory of Pediatrics, Chongqing, 400014, PR China.
  • 4 Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, PR China; Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing, 400014, PR China; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, 400014, PR China; National Clinical Research Center for Child Health and Disorders, Chongqing, 400014, PR China; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, 400014, PR China; Chongqing Key Laboratory of Pediatrics, Chongqing, 400014, PR China. Electronic address: hedawei@hospital.cqmu.edu.cn.
PMID: 36736526 DOI: 10.1016/j.ejphar.2023.175523
Abstract

Bladder outlet obstruction (BOO) can cause serious complications including kidney damage; nevertheless, there are currently no animal models for studying BOO-induced kidney damage. Mesenchymal stem cells (MSCs) are widely used in therapeutic studies of renal fibrosis. However, MSC-derived exosomes show improved safety profile and more controllable characteristics compared with those of MSCs. Herein, we established a kidney injury mouse model of partial bladder outlet obstruction (PBOO) and evaluated the effects of human umbilical cord MSC-derived exosomes (hucMSC-Exos) on PBOO-induced reflux kidney injury in this model. Exosomes were isolated from a hucMSC-conditioned medium, purified by ultracentrifugation, and examined. Living image was performed to indicate the distribution of hucMSC-Exos. The PBOO-treated mice interacted with PBS (phosphate-buffered saline) or hucMSC-Exos. Morphologic changes and expression of interstitial-fibrosis-related, cell proliferation and Wnt/β-catenin signaling-pathway indices were evaluated. At 7 days after induction of PBOO, structural destruction of renal tubules was observed. Expression of the interstitial markers and the cellular-proliferation index increased significantly in the PBOO group compared with the control group (p < 0.05). The isolated exosomes were 30-150 nm in diameter, showing a round shape and bilayer membrane structure with CD63, TSG101, Alix expressed, enriched in the kidney of the PBOO group. Administering hucMSC-Exos to post-PBOO mice reversed renal injury and suppressed expression of Wnt/β-catenin signaling pathway-related proteins. hucMSC-Exos inhibited PBOO-induced kidney injury and cellular proliferation and suppressed the Wnt/β-catenin signaling pathway. Our findings will spur the development of novel hucMSC-Exo-mediated therapies for treating patients with renal fibrosis.

Keywords

Chronic kidney disease; Exosomes; Kidney injury; Mesenchymal stem cells; Partial bladder outlet obstruction; Wnt/β-catenin signaling pathway.

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