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
  • 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: [email protected].
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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