PMID- 37240246 OWN - NLM STAT- MEDLINE DCOM- 20230529 LR - 20230529 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 24 IP - 10 DP - 2023 May 17 TI - Human Umbilical Cord Mesenchymal Stem Cells Protect against Renal Ischemia-Reperfusion Injury by Secreting Extracellular Vesicles Loaded with miR-148b-3p That Target Pyruvate Dehydrogenase Kinase 4 to Inhibit Endoplasmic Reticulum Stress at the Reperfusion Stages. LID - 10.3390/ijms24108899 [doi] LID - 8899 AB - Renal ischemia-reperfusion (I/R) injury is a leading cause of acute kidney injury (AKI), with high mortality. Recent studies have reported that human umbilical cord mesenchymal stem cells (HucMSCs) play an important role in repairing organ and tissue injuries because of their unique characteristics. However, the potential of HucMSC extracellular vesicles (HucMSC-EVs) to promote the repair of renal tubular cells remains to be explored. This study found that HucMSC-EVs derived from HucMSCs played a protective role and were associated with kidney I/R injury. We found that miR-148b-3p in HucMSC-EVs had a protective effect against kidney I/R injury. HK-2 cells overexpressing miR-148b-3p were protected against I/R injury by inhibiting apoptosis. Next, the target mRNA of miR-148b-3p was predicted online, and the target mRNA, pyruvate dehydrogenase kinase 4 (PDK4), was identified and verified using dual luciferase. We discovered that I/R injury significantly increased endoplasmic reticulum (ER) stress, whereas siR-PDK4 inhibited these effects and protected against I/R injury. Interestingly, after administrating HucMSC-EVs to HK-2 cells, PDK4 expression and ER stress induced by I/R injury were significantly inhibited. HK-2 ingested miR-148b-3p from HucMSC-EVs, and its ER induced by I/R injury was significantly deregulated. This study suggests that HucMSC-EVs protect kidneys from I/R injury during the early I/R stage. These results suggest a new mechanism for HucMSC-EVs in treating AKI and provide a new treatment strategy for I/R injury. FAU - Shi, Wei AU - Shi W AUID- ORCID: 0009-0008-8078-3872 AD - Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. AD - Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. FAU - Zhou, Xiang AU - Zhou X AD - Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. AD - Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. FAU - Li, Xinyuan AU - Li X AD - Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. AD - Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. FAU - Peng, Xiang AU - Peng X AD - Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. AD - Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. FAU - Chen, Guo AU - Chen G AD - Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. AD - Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. FAU - Li, Yang AU - Li Y AD - Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. AD - Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. FAU - Zhang, Chunlin AU - Zhang C AD - Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. AD - Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. FAU - Yu, Haitao AU - Yu H AUID- ORCID: 0000-0002-9745-8418 AD - Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. AD - Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. FAU - Feng, Zhenwei AU - Feng Z AD - Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. AD - Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. FAU - Gou, Xin AU - Gou X AD - Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. FAU - Fan, Jing AU - Fan J AD - Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. LA - eng GR - cstc2020jcyj-msxmX0285/Science and Technology Commission of Chongqing/ PT - Journal Article DEP - 20230517 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - EC 2.7.1.- (pyruvate dehydrogenase kinase 4) RN - 0 (MicroRNAs) SB - IM MH - Humans MH - Kidney/metabolism MH - *Extracellular Vesicles/metabolism MH - *Acute Kidney Injury/metabolism MH - *Reperfusion Injury/genetics/metabolism MH - *MicroRNAs/genetics/metabolism MH - Reperfusion MH - *Mesenchymal Stem Cells/metabolism MH - Endoplasmic Reticulum Stress/genetics MH - Umbilical Cord/metabolism PMC - PMC10219505 OTO - NOTNLM OT - MicroRNA OT - apoptosis OT - endoplasmic reticulum stress OT - extracellular vesicles OT - human umbilical cord mesenchymal stem cells OT - ischemia/reperfusion injury COIS- The authors declare that there are no conflict of interest. EDAT- 2023/05/27 09:42 MHDA- 2023/05/29 06:42 PMCR- 2023/05/17 CRDT- 2023/05/27 01:15 PHST- 2023/03/28 00:00 [received] PHST- 2023/05/10 00:00 [revised] PHST- 2023/05/15 00:00 [accepted] PHST- 2023/05/29 06:42 [medline] PHST- 2023/05/27 09:42 [pubmed] PHST- 2023/05/27 01:15 [entrez] PHST- 2023/05/17 00:00 [pmc-release] AID - ijms24108899 [pii] AID - ijms-24-08899 [pii] AID - 10.3390/ijms24108899 [doi] PST - epublish SO - Int J Mol Sci. 2023 May 17;24(10):8899. doi: 10.3390/ijms24108899.