PMID- 32786312 OWN - NLM STAT- MEDLINE DCOM- 20210618 LR - 20220531 IS - 1948-7193 (Electronic) IS - 1948-7193 (Linking) VI - 11 IP - 17 DP - 2020 Sep 2 TI - MG53 Protects hUC-MSCs against Inflammatory Damage and Synergistically Enhances Their Efficacy in Neuroinflammation Injured Brain through Inhibiting NLRP3/Caspase-1/IL-1beta Axis. PG - 2590-2601 LID - 10.1021/acschemneuro.0c00268 [doi] AB - The inflammatory microenvironment in a lesion is not conducive to the survival of stem cells. Improving the inflammatory microenvironment may be an alternative strategy to enhance the efficacy of stem cells. We evaluated the therapeutic effect and molecular mechanism of mitsugumin53 (MG53) on lipopolysaccharide (LPS)-induced damage in human umbilical cord mesenchymal stem cells (hUC-MSCs) and in C57/BL6 mice. MG53 significantly promoted the proliferation and migration of hUC-MSCs, protected hUC-MSCs against LPS-induced apoptosis and mitochondrial dysfunction, and reversed LPS-induced inflammatory cytokine release. Furthermore, MG53 combined with hUC-MSCs transplantation improved LPS-induced memory impairment and activated neurogenesis by promoting the migration of hUC-MSCs and enhancing betaIII-tubulin and doublecortin (DCX) expression. MG53 protein combined with hUC-MSCs improved the M1/M2 phenotype polarization of microglia accompanied by lower inducible nitric oxide synthase (iNOS) expression and higher arginase 1 (ARG1) expression. MG53 significantly suppressed the expression of tumor necrosis factor alpha (TNF-alpha), Toll-like receptor 4 (TLR4), nucleotide oligomerization domain-like receptor protein 3 (NLRP3), cleaved-caspase-1, and interleukin (IL)-1beta to alleviate LPS-induced neuroinflammation on hUC-MSCs and C57/BL6 mice. In conclusion, our results indicated that MG53 could protect hUC-MSCs against LPS-induced inflammatory damage and facilitate their efficacy in LPS-treated C57/BL6 mice partly by inhibiting the NLRP3/caspase-1/IL-1beta axis. FAU - Ma, Shanshan AU - Ma S AUID- ORCID: 0000-0002-0780-4568 AD - School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 Henan, China. AD - Institute of Neuroscience, Zhengzhou University, Zhengzhou, 450052 Henan, China. FAU - Wang, Yaping AU - Wang Y AD - School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 Henan, China. FAU - Zhou, Xinkui AU - Zhou X AD - School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 Henan, China. FAU - Li, Zhe AU - Li Z AD - School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 Henan, China. FAU - Zhang, Zhenkun AU - Zhang Z AD - School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 Henan, China. FAU - Wang, Yingying AU - Wang Y AD - School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 Henan, China. FAU - Huang, Tuanjie AU - Huang T AD - School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 Henan, China. FAU - Zhang, Yanting AU - Zhang Y AD - School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 Henan, China. FAU - Shi, Jijing AU - Shi J AD - Central Lab of the First People's Hospital of Zhengzhou, Zhengzhou, 450001 Henan. China. FAU - Guan, Fangxia AU - Guan F AD - School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 Henan, China. AD - Institute of Neuroscience, Zhengzhou University, Zhengzhou, 450052 Henan, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200817 PL - United States TA - ACS Chem Neurosci JT - ACS chemical neuroscience JID - 101525337 RN - 0 (Dcx protein, mouse) RN - 0 (Doublecortin Protein) RN - 0 (MG53 protein, mouse) RN - 0 (Membrane Proteins) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Nlrp3 protein, mouse) RN - EC 3.4.22.36 (Caspase 1) SB - IM MH - Animals MH - Brain MH - Caspase 1 MH - Doublecortin Protein MH - Membrane Proteins MH - *Mesenchymal Stem Cell Transplantation MH - Mice MH - *NLR Family, Pyrin Domain-Containing 3 Protein MH - Umbilical Cord OTO - NOTNLM OT - LPS OT - MG53 OT - NLRP3 inflammasome OT - hUC-MSCs OT - neuroinflammation EDAT- 2020/08/14 06:00 MHDA- 2021/06/22 06:00 CRDT- 2020/08/14 06:00 PHST- 2020/08/14 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/08/14 06:00 [entrez] AID - 10.1021/acschemneuro.0c00268 [doi] PST - ppublish SO - ACS Chem Neurosci. 2020 Sep 2;11(17):2590-2601. doi: 10.1021/acschemneuro.0c00268. Epub 2020 Aug 17.