PMID- 37293812 OWN - NLM STAT- MEDLINE DCOM- 20230612 LR - 20230614 IS - 1525-6049 (Electronic) IS - 0886-022X (Print) IS - 0886-022X (Linking) VI - 45 IP - 1 DP - 2023 Dec TI - Human umbilical cord mesenchymal stem cell exosomes alleviate acute kidney injury by inhibiting pyroptosis in rats and NRK-52E cells. PG - 2221138 LID - 10.1080/0886022X.2023.2221138 [doi] LID - 2221138 AB - Human umbilical cord mesenchymal stem cells (hucMSCs) have been shown to improve kidney injury. Exosomes have been indicated to be important mediators of renal protection in MSC therapy. In spite of this, the mechanism remains unclear. Our study investigated how exosomes derived from hucMSCs (hucMSC-Ex) improve acute kidney injury (AKI). Exosomes were extracted by using an ultracentrifugation technique and identified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot. Twenty-four male SD rats were randomly divided into four groups: sham group, sham + hucMSC-Ex group, ischemia-reperfusion injury (IRI) group, and IRI + hucMSC-Ex group. In vitro, we treated rat proximal renal tubular epithelial cell line (NRK-52E) with cisplatin to mimic in vivo models of AKI. The NRK-52E cells were treated with or without 160 mug/mL hucMSC-Ex, and 1 microg/mL cisplatin was added after 9 h. Cells were harvested after 24 h. In the IRI group, the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) were increased; renal tubules were dilated, epithelial cells were vacuolated, and collagen fibers were deposited in the renal interstitium. After treatment with cisplatin, the NRK-52E cells displayed pyroptotic morphology characterized by pyroptotic bodies. The protein expression levels of fibronectin, alpha-smooth muscle actin (alpha-SMA), vimentin, gasdermin D (GSDMD), caspase-1, interleukin-1 (IL-1beta) and NLRP3 in IRI tissues and in cisplatin treatment NRK-52E cells were significantly upregulated. However, after the hucMSC-Ex intervention, kidney injury was effectively improved in vivo and in vitro. The current study shows that pyroptosis is involved in AKI and that hucMSC-Ex improves AKI by inhibiting pyroptosis. FAU - Wan, Yonghong AU - Wan Y AD - Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, PR China. AD - Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, PR China. AD - Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing Key Laboratory of Pediatrics, Chongqing, PR China. AD - Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, PR China. AD - National Clinical Research Center for Child Health and Disorders, Chongqing, PR China. AD - China International Science and Technology Cooperation base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, PR China. FAU - Yu, Yihang AU - Yu Y AD - Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, PR China. AD - Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, PR China. AD - Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing Key Laboratory of Pediatrics, Chongqing, PR China. AD - Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, PR China. AD - National Clinical Research Center for Child Health and Disorders, Chongqing, PR China. AD - China International Science and Technology Cooperation base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, PR China. FAU - Yu, Chengjun AU - Yu C AD - Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, PR China. AD - Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, PR China. AD - Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing Key Laboratory of Pediatrics, Chongqing, PR China. AD - Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, PR China. AD - National Clinical Research Center for Child Health and Disorders, Chongqing, PR China. AD - China International Science and Technology Cooperation base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, PR China. FAU - Luo, Jin AU - Luo J AD - Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, PR China. AD - Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, PR China. AD - Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing Key Laboratory of Pediatrics, Chongqing, PR China. AD - Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, PR China. AD - National Clinical Research Center for Child Health and Disorders, Chongqing, PR China. AD - China International Science and Technology Cooperation base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, PR China. FAU - Wen, Sheng AU - Wen S AD - Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, PR China. AD - Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing Key Laboratory of Pediatrics, Chongqing, PR China. AD - Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, PR China. AD - National Clinical Research Center for Child Health and Disorders, Chongqing, PR China. AD - China International Science and Technology Cooperation base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, PR China. FAU - Shen, Lianju AU - Shen L AD - Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, PR China. AD - Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing Key Laboratory of Pediatrics, Chongqing, PR China. AD - Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, PR China. AD - National Clinical Research Center for Child Health and Disorders, Chongqing, PR China. AD - China International Science and Technology Cooperation base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, PR China. FAU - Wei, Guanghui AU - Wei G AD - Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, PR China. AD - Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing Key Laboratory of Pediatrics, Chongqing, PR China. AD - Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, PR China. AD - National Clinical Research Center for Child Health and Disorders, Chongqing, PR China. AD - China International Science and Technology Cooperation base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, PR China. FAU - Hua, Yi AU - Hua Y AD - Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, PR China. AD - Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing Key Laboratory of Pediatrics, Chongqing, PR China. AD - Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, PR China. AD - National Clinical Research Center for Child Health and Disorders, Chongqing, PR China. AD - China International Science and Technology Cooperation base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, PR China. LA - eng PT - Journal Article PL - England TA - Ren Fail JT - Renal failure JID - 8701128 RN - Q20Q21Q62J (Cisplatin) SB - IM MH - Rats MH - Humans MH - Male MH - Animals MH - *Exosomes/metabolism MH - Pyroptosis MH - Rats, Sprague-Dawley MH - Cisplatin/pharmacology MH - *Acute Kidney Injury/therapy/metabolism MH - Umbilical Cord MH - *Mesenchymal Stem Cells/metabolism PMC - PMC10259332 OTO - NOTNLM OT - Exosomes OT - acute kidney injury OT - hucMSC OT - pyroptosis COIS- No potential conflict of interest was reported by the author(s). EDAT- 2023/06/09 06:42 MHDA- 2023/06/12 06:42 PMCR- 2023/06/09 CRDT- 2023/06/09 05:33 PHST- 2023/06/12 06:42 [medline] PHST- 2023/06/09 06:42 [pubmed] PHST- 2023/06/09 05:33 [entrez] PHST- 2023/06/09 00:00 [pmc-release] AID - 2221138 [pii] AID - 10.1080/0886022X.2023.2221138 [doi] PST - ppublish SO - Ren Fail. 2023 Dec;45(1):2221138. doi: 10.1080/0886022X.2023.2221138.