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

被引：7

作者：

Wang, Zhaoying ^{[3
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Yu, Yihang ^{[3
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Jin, Liming ^{[3
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Tan, Xiaojun ^{[3
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Liu, Bo ^{[2
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Zhang, Zhaoxia ^{[3
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]}

Wang, Zhang ^{[3
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Long, Chunlan ^{[3
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Shen, Lianju ^{[3
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]}

Wei, Guanghui ^{[1
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He, Dawei ^{[1
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,7
]}

机构：

[1] Chongqing Med Univ, Dept Urol, Childrens Hosp, Chongqing 400014, Peoples R China

[2] Chongqing Med Univ, Dept Cardiothorac Surg, Childrens Hosp, Chongqing 400014, Peoples R China

[3] Children Urogenital Dev & Tissue Engn, Chongqing Key Lab, Chongqing 400014, Peoples R China

[4] Minist Educ, Key Lab Child Dev & Disorders, Chongqing 400014, Peoples R China

[5] Natl Clin Res Ctr Child Hlth & Disorders, Chongqing 400014, Peoples R China

[6] China Int Sci & Technol Cooperat Base Child Dev &, Chongqing 400014, Peoples R China

[7] Chongqing Key Lab Pediat, Chongqing 400014, Peoples R China

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 2023年 / 952卷

关键词：

Partial bladder outlet obstruction; Kidney injury; Chronic kidney disease; Mesenchymal stem cells; Exosomes; Wnt/beta-catenin signaling pathway; URINARY-TRACT; FIBROSIS; NEPHRECTOMY; THERAPY; KIDNEY; MEN;

D O I：

10.1016/j.ejphar.2023.175523

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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/beta-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. 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/beta-catenin signaling pathway-related proteins. hucMSC-Exos inhibited PBOO-induced kidney injury and cellular proliferation and suppressed the Wnt/beta-catenin signaling pathway. Our findings will spur the development of novel hucMSC-Exo-mediated therapies for treating patients with renal fibrosis.

引用

页数：10

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