PMID- 30321544 OWN - NLM STAT- MEDLINE DCOM- 20181211 LR - 20181211 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 214 DP - 2018 Dec 1 TI - Protective effects of SOD2 overexpression in human umbilical cord mesenchymal stem cells on lung injury induced by acute paraquat poisoning in rats. PG - 11-21 LID - S0024-3205(18)30637-4 [pii] LID - 10.1016/j.lfs.2018.10.020 [doi] AB - AIMS: To study the protective effects and mechanisms of human umbilical cord mesenchymal stem cells (hUCMSCs) and overexpression of antioxidant gene SOD2 on lung injury by establishing a rat model of paraquat (PQ)-induced lung injury. MAIN METHODS: The hUCMSCs cell line overexpressed SOD2 was established. After intraperitoneal injection of PQ solution (24 mg/kg) 3 h later, the different groups of hUCMSCs cell lines were injected through the tail veins of rats. Bronchoalveolar lavage fluid (BALF) was obtained to determine the protein level of inflammatory cytokines. Lung tissues were collected to test the wet/dry weight ratios (W/D), oxidative stress index and lung injury scores. Western blotting was used to detect SOD1, SOD2, HO-1, Nrf2, NF-kappaBp65 subunit, and cleaved caspase-3. KEY FINDINGS: After treatment with cells built on the basis of hUCMSCs, the protein levels of TNF-alpha, IL-8, and ICAM-1 in BALF decreased, and meanwhile in lung tissues, MDA content was reduced, GSH-Px activity was elevated, and lung W/D ratio decreased. Additionally, protein expression of NF-kappaB p65 subunit and activated caspase-3 in lung tissues was down-regulated, whereas expression of SOD1, SOD2, HO-1, and Nrf-2 were up-regulated. The results of HE staining showed that lung injury was significantly alleviated in the hUCMSC treated group. It is noticeable that hUCMSCs and SOD2-overexpressed hUCMSCs effectively reduced PQ-induced lung injury in rats, and moreover, hUCMSCs overexpressed SOD2 were more effective compared with hUCMSCs only. SIGNIFICANCE: Evaluation of the efficacy and analysis of mechanism in the treatment of PQ induced ALI by appliance of SOD2-overexpressed hUCMSCs will provide the proof from bench to bedside. CI - Copyright (c) 2018 Elsevier Inc. All rights reserved. FAU - Zhang, Li-Chun AU - Zhang LC AD - Emergency Department of Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning Province 110004, China. Electronic address: zhanglc@sj-hospital.org. FAU - Wang, Yu AU - Wang Y AD - Emergency Department of Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning Province 110004, China. FAU - Liu, Wei AU - Liu W AD - Emergency Department of Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning Province 110004, China. FAU - Zhang, Xue-Min AU - Zhang XM AD - Eugenom Inc., Rm 310 No. 226 North Nanjing Street, Heping District, Shenyang, Liaoning Province 110001, China. FAU - Fan, Miao AU - Fan M AD - Eugenom Inc., Rm 310 No. 226 North Nanjing Street, Heping District, Shenyang, Liaoning Province 110001, China. FAU - Zhao, Min AU - Zhao M AD - Emergency Department of Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning Province 110004, China. LA - eng PT - Journal Article DEP - 20181012 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (Cytokines) RN - 0 (Transcription Factor RelA) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 1.15.1.1 (superoxide dismutase 2) RN - PLG39H7695 (Paraquat) SB - IM MH - Acute Lung Injury/*chemically induced/metabolism/pathology/*therapy MH - Animals MH - Bronchoalveolar Lavage Fluid/cytology MH - Cells, Cultured MH - Cytokines/metabolism MH - Heme Oxygenase-1/metabolism MH - Humans MH - Infant, Newborn MH - Male MH - Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/cytology/*metabolism MH - Oxidative Stress MH - Paraquat/*poisoning MH - Rats, Wistar MH - Superoxide Dismutase/genetics/*metabolism MH - Transcription Factor RelA/metabolism MH - Transgenes OTO - NOTNLM OT - Acute paraquat poisoning OT - Human umbilical cord mesenchymal stem cells OT - Lung injury OT - Nuclear factor erythroid 2-related factor OT - Superoxide dismutase 2 EDAT- 2018/10/16 06:00 MHDA- 2018/12/12 06:00 CRDT- 2018/10/16 06:00 PHST- 2018/07/28 00:00 [received] PHST- 2018/10/10 00:00 [revised] PHST- 2018/10/11 00:00 [accepted] PHST- 2018/10/16 06:00 [pubmed] PHST- 2018/12/12 06:00 [medline] PHST- 2018/10/16 06:00 [entrez] AID - S0024-3205(18)30637-4 [pii] AID - 10.1016/j.lfs.2018.10.020 [doi] PST - ppublish SO - Life Sci. 2018 Dec 1;214:11-21. doi: 10.1016/j.lfs.2018.10.020. Epub 2018 Oct 12.