PMID- 31015841 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220408 IS - 1687-966X (Print) IS - 1687-9678 (Electronic) VI - 2019 DP - 2019 TI - Exosomes from Human Umbilical Cord Mesenchymal Stem Cells Reduce Damage from Oxidative Stress and the Epithelial-Mesenchymal Transition in Renal Epithelial Cells Exposed to Oxalate and Calcium Oxalate Monohydrate. PG - 6935806 LID - 10.1155/2019/6935806 [doi] LID - 6935806 AB - OBJECTIVE: To investigate whether exosomes from human umbilical cord mesenchymal stem cells (hUC-MSCs) can protect against the toxic effects of oxalate and calcium oxalate monohydrate (COM) crystals in human proximal tubular epithelial (HK-2) cells. METHODS: Exosomes were isolated from hUC-MSCs, purified by ultracentrifugation, and verified by examination of cell morphology using transmission electron microscopy and the presence of specific biomarkers. HK-2 cells received 1 of 4 treatments: control (cells alone), hUC-MSC exosomes, oxalate+COM, or oxalate+COM and hUC-MSC exosomes. Cell viability was determined using the MTT assay. Oxidative stress was determined by measuring LDH activity and the levels of H(2)O(2), malondialdehyde (MDA), and reactive oxygen species (ROS). Expressions of N-cadherin, TGF-beta, and ZO-1 were determined by immunofluorescence. Expressions of epithelial markers, mesenchymal markers, and related signaling pathway proteins were determined by western blotting. RESULTS: After 48 h, cells in the oxalate+COM group lost their adhesion, appeared long, spindle-shaped, and scattered, and the number of cells had significantly decreased. The oxalate+COM treatment also upregulated TGF-beta and mesenchymal markers, downregulated epithelial markers, increased the levels of LDH, H(2)O(2), MDA, and ROS, decreased cell viability, and increased cell migration. The isolated exosomes had double-layer membranes, had hollow, circular, or elliptical shapes, had diameters mostly between 30 and 100 nm, and expressed CD9, CD63, and Alix. Treatment of HK-2 cells with hUC-MSC exosomes reversed or partly reversed all the effects of oxalate+COM. CONCLUSIONS: Exosomes from hUC-MSCs alleviate the oxidative injury and the epithelial-mesenchymal transformation of HK-2 cells that is induced by oxalate+COM. FAU - Li, Dian AU - Li D AUID- ORCID: 0000-0002-8350-8648 AD - Chongqing Key Laboratory of Child Urogenital Development and Tissue Engineering, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China. FAU - Zhang, Dan AU - Zhang D AUID- ORCID: 0000-0003-4590-337X AD - Chongqing Key Laboratory of Child Urogenital Development and Tissue Engineering, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China. FAU - Tang, Bo AU - Tang B AD - Chongqing Key Laboratory of Child Urogenital Development and Tissue Engineering, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China. FAU - Zhou, Yue AU - Zhou Y AD - Chongqing Key Laboratory of Child Urogenital Development and Tissue Engineering, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China. FAU - Guo, Wenhao AU - Guo W AUID- ORCID: 0000-0003-1717-7585 AD - Chongqing Key Laboratory of Child Urogenital Development and Tissue Engineering, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China. FAU - Kang, Qing AU - Kang Q AD - Chongqing Key Laboratory of Child Urogenital Development and Tissue Engineering, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China. FAU - Wang, Zhang AU - Wang Z AUID- ORCID: 0000-0002-6661-7674 AD - Chongqing Key Laboratory of Child Urogenital Development and Tissue Engineering, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China. FAU - Shen, Lianju AU - Shen L AUID- ORCID: 0000-0001-8973-5393 AD - Chongqing Key Laboratory of Child Urogenital Development and Tissue Engineering, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China. FAU - Wei, Guanghui AU - Wei G AUID- ORCID: 0000-0002-7822-8684 AD - Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing 400014, China. FAU - He, Dawei AU - He D AUID- ORCID: 0000-0003-1548-424X AD - Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing 400014, China. LA - eng PT - Journal Article DEP - 20190319 PL - United States TA - Stem Cells Int JT - Stem cells international JID - 101535822 PMC - PMC6444261 EDAT- 2019/04/25 06:00 MHDA- 2019/04/25 06:01 PMCR- 2019/03/19 CRDT- 2019/04/25 06:00 PHST- 2018/12/01 00:00 [received] PHST- 2019/01/24 00:00 [revised] PHST- 2019/02/14 00:00 [accepted] PHST- 2019/04/25 06:00 [entrez] PHST- 2019/04/25 06:00 [pubmed] PHST- 2019/04/25 06:01 [medline] PHST- 2019/03/19 00:00 [pmc-release] AID - 10.1155/2019/6935806 [doi] PST - epublish SO - Stem Cells Int. 2019 Mar 19;2019:6935806. doi: 10.1155/2019/6935806. eCollection 2019.