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Current Stem Cell Research & Therapy

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ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

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Research Article

Attenuation of Lipopolysaccharide-induced Liver Injury by Bone Marrow Mesenchymal Stem Cells via Inhibiting the NLRP3 Inflammasome and Hepatocyte Pyroptosis

Author(s): Yunyu Yin, Lu Tang, Kui Liu, Xuefeng Ding, Daqing Wang and Li Chen*

Volume 17, Issue 4, 2022

Published on: 12 May, 2022

Page: [361 - 369] Pages: 9

DOI: 10.2174/1574888X17666220407103441

Price: $65

Abstract

Background: The transplantation of bone marrow mesenchymal cells (BMSCs) has been shown to be an effective mean for treating sepsis-related organ damage. Pytoptotic cell death, in turn, has recently been identified as a key driver of sepsis-related damage. At present, there are few studies on the effect of BMSC transplantation on pyroptotic cell death.

Objective: We explored the ability of BMSCs to attenuate hepatic damage in a pyroptosis-related manner in a rat model of lipopolysaccharide (LPS)-induced liver injury.

Methods: Following injury modeling and BMSC transplantation, we assessed the expression of the NLR family, pyrin domain containing 3 (NLRP3) inflammasome, and key downstream pyroptosis-related signaling molecules.

Results: It was found that BMSC transplantation was sufficient to significantly improve rat survival after LPS injection. A significantly reduced expression of the pyroptosis-related proteins NLRP3, caspase-1, IL-1β, and IL-18 in rats that had undergone BMSC transplantation compared to control animals was observed. Notably, this activity was superior to single-agent administration of the NLRP3 inhibitor MCC950.

Conclusion: Our data suggest that BMSC transplantation may alleviate LPS-induced hepatic damage by suppressing the activation of the NLRP3 inflammasome and the induction of pyroptotic cell death.

Keywords: Bone marrow mesenchymal stem cells, liver injury, pyroptosis, NLRP3 inflammasome, Hepatocyte Pyroptosis, BMSC transplantation, lipopolysaccharide.

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Graphical Abstract

[1]
Kobashi H, Toshimori J, Yamamoto K. Sepsis-associated liver injury: Incidence, classification and the clinical significance. Hepatol Res 2013; 43(3): 255-66.
[http://dx.doi.org/10.1111/j.1872-034X.2012.01069.x] [PMID: 22971102]
[2]
Zhang F, Wang X, Qiu X, et al. The protective effect of Esculentoside A on experimental acute liver injury in mice. PLoS One 2014; 9(11): e113107.
[http://dx.doi.org/10.1371/journal.pone.0113107] [PMID: 25405982]
[3]
Bal F, Bekpinar S, Unlucerci Y, et al. Antidiabetic drug metformin is effective on the metabolism of asymmetric dimethylarginine in exper-imental liver injury. Diabetes Res Clin Pract 2014; 106(2): 295-302.
[http://dx.doi.org/10.1016/j.diabres.2014.08.028] [PMID: 25263501]
[4]
Jiang R, Chen X, Ge S, et al. MiR-21-5p induces pyroptosis in colorectal cancer via TGFBI. Front Oncol 2021; 10: 610545.
[http://dx.doi.org/10.3389/fonc.2020.610545] [PMID: 33614494]
[5]
Doitsh G, Galloway NL, Geng X, et al. Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection. Nature 2014; 505(7484): 509-14.
[http://dx.doi.org/10.1038/nature12940] [PMID: 24356306]
[6]
Wang YC, Liu QX, Liu T, et al. Caspase-1-dependent pyroptosis of peripheral blood mononuclear cells predicts the development of sep-sis in severe trauma patients: A prospective observational study. Medicine (Baltimore) 2018; 97(8): e9859.
[http://dx.doi.org/10.1097/MD.0000000000009859] [PMID: 29465571]
[7]
Chen Q, Yang Y, Hou J, et al. Increased gene copy number of DEFA1/DEFA3 worsens sepsis by inducing endothelial pyroptosis. Proc Natl Acad Sci USA 2019; 116(8): 3161-70.
[http://dx.doi.org/10.1073/pnas.1812947116] [PMID: 30718392]
[8]
Liu Y, Li P, Qiao C, et al. Chitosan hydrogel enhances the therapeutic efficacy of bone marrow–derived mesenchymal stem cells for myo-cardial infarction by alleviating vascular endothelial cell pyroptosis. J Cardiovasc Pharmacol 2020; 75(1): 75-83.
[http://dx.doi.org/10.1097/FJC.0000000000000760] [PMID: 31663873]
[9]
Jia Y, Cui R, Wang C, et al. Metformin protects against intestinal ischemia-reperfusion injury and cell pyroptosis via TXNIP-NLRP3-GSDMD pathway. Redox Biol 2020; 32: 101534.
[http://dx.doi.org/10.1016/j.redox.2020.101534] [PMID: 32330868]
[10]
Zhang Y, Hao J, Ma X, et al. Huoxue jiedu huayu recipe ameliorates mesangial cell pyroptosis in contralateral kidney of UUO rats. Evid Based Complement Alternat Med 2020; 2020(5): 2530431.
[http://dx.doi.org/10.1155/2020/2530431] [PMID: 33456483]
[11]
Xu B, Jiang MZ, Chu Y, Wang WJ, Chen D, Li XW, et al. Gasdermin D plays a key role as a pyroptosis executor of non-alcoholic steato-hepatitis in humans and mice. J Hepatol 2017; (Nov): S0168827817324947.
[PMID: 29273476]
[12]
Li H, Zhao XK, Cheng YJ, et al. Gasdermin D-mediated hepatocyte pyroptosis expands inflammatory responses that aggravate acute liver failure by upregulating monocyte chemotactic protein 1/CC chemokine receptor-2 to recruit macrophages. World J Gastroenterol 2019; 25(44): 6527-40.
[http://dx.doi.org/10.3748/wjg.v25.i44.6527] [PMID: 31802832]
[13]
Xie WH, Ding J, Xie XX, et al. Hepatitis B virus X protein promotes liver cell pyroptosis under oxidative stress through NLRP3 inflam-masome activation. Inflamm Res 2020; 69(7): 683-96.
[http://dx.doi.org/10.1007/s00011-020-01351-z] [PMID: 32347316]
[14]
Chen YL, Xu G, Liang X, et al. Inhibition of hepatic cells pyroptosis attenuates CLP-induced acute liver injury. Am J Transl Res 2016; 8(12): 5685-95.
[PMID: 28078039]
[15]
Zhang J, Sun X, Zhong L, Shen B. IL-32 exacerbates adenoid hypertrophy via activating NLRP3-mediated cell pyroptosis, which pro-motes inflammation. Mol Med Rep 2021; 23(3): 226.
[http://dx.doi.org/10.3892/mmr.2021.11865] [PMID: 33495843]
[16]
Li JY, Wang YY, Shao T, et al. The zebrafish NLRP3 inflammasome has functional roles in ASC-dependent interleukin-1β maturation and gasdermin E-mediated pyroptosis. J Biol Chem 2020; 295(4): 1120-41.
[http://dx.doi.org/10.1016/S0021-9258(17)49920-0] [PMID: 31852739]
[17]
Hou L, Yang Z, Wang Z, et al. NLRP3/ASC-mediated alveolar macrophage pyroptosis enhances HMGB1 secretion in acute lung injury induced by cardiopulmonary bypass. Lab Invest 2018; 98(8): 1052-64.
[http://dx.doi.org/10.1038/s41374-018-0073-0] [PMID: 29884910]
[18]
Liu Y, Jing YY, Zeng CY, et al. Scutellarin suppresses NLRP3 inflammasome activation in macrophages and protects mice against bacteri-al sepsis. Front Pharmacol 2018; 8: 975.
[http://dx.doi.org/10.3389/fphar.2017.00975] [PMID: 29375379]
[19]
Heo MJ, Kim TH, You JS, Blaya D, Sancho-Bru P, Kim SG. Alcohol dysregulates miR-148a in hepatocytes through FoxO1, facilitating pyroptosis via TXNIP overexpression. Gut 2019; 68(4): 708-20.
[http://dx.doi.org/10.1136/gutjnl-2017-315123] [PMID: 29475852]
[20]
Khanova E, Wu R, Wang W, et al. Pyroptosis by caspase11/4-gasdermin-D pathway in alcoholic hepatitis in mice and patients. Hepatology 2018; 67(5): 1737-53.
[http://dx.doi.org/10.1002/hep.29645] [PMID: 29108122]
[21]
Xu B, Gan CX, Chen SS, Li JQ, Liu MZ, Guo GH. BMSC-derived exosomes alleviate smoke inhalation lung injury through blockade of the HMGB1/NF-κB pathway. Life Sci 2020; 257: 118042.
[22]
Kang KN, Kim DY, Yoon SM, et al. Tissue engineered regeneration of completely transected spinal cord using human mesenchymal stem cells. Biomaterials 2012; 33(19): 4828-35.
[http://dx.doi.org/10.1016/j.biomaterials.2012.03.043] [PMID: 22498301]
[23]
Mohi El-Din MM, Rashed LA, Mahmoud Haridy MA, Khalil AM, Albadry MM. Impact of bone marrow-derived mesenchymal stem cells on remodeling the lung injury induced by liplipopolysaccharides in mice. Future Science 2017; 3(1): FSO162.
[24]
Wang M, Zhang X, Xiong XI, et al. Bone marrow mesenchymal stem cells reverse liver damage in a carbon tetrachlorideinduced mouse mModel of chronic liver injury. In Vivo 2016; 30(3): 187-93.
[PMID: 27107074]
[25]
Darkazalli A, Vied C, Badger CD, Levenson CW. Human mMesenchymal stem cell treatment normalizes cortical gene expression after traumatic brain injury. J Neurotrauma 2017; 34(1): 204-12.
[http://dx.doi.org/10.1089/neu.2015.4322] [PMID: 27161121]
[26]
Zhao Y, Gibb SL, Zhao J, et al. Wnt3a, a protein secreted by mesenchymal stem cells is neuroprotective and promotes neurocognitive recovery following traumatic brain injury. Stem Cells 2016; 34(5): 1263-72.
[http://dx.doi.org/10.1002/stem.2310] [PMID: 26840479]
[27]
Cízková D, Rosocha J, Vanický I, Jergová S, Cízek M. Transplants of human mesenchymal stem cells improve functional recovery after spinal cord injury in the rat. Cell Mol Neurobiol 2006; 26(7-8): 1167-80.
[http://dx.doi.org/10.1007/s10571-006-9093-1] [PMID: 16897366]
[28]
Zhao FY, Cheng TY, Yang L, et al. G-CSF Inhibits pulmonary fibrosis by promoting BMSC homing to the lungs via SDF-1/CXCR4 chem-otaxis. Sci Rep 2020; 10(1): 10515.
[http://dx.doi.org/10.1038/s41598-020-65580-2] [PMID: 32601321]
[29]
Zhang GW, Gu TX, Guan XY, et al. HGF and IGF-1 promote protective effects of allogeneic BMSC transplantation in rabbit model of acute myocardial infarction. Cell Prolif 2015; 48(6): 661-70.
[http://dx.doi.org/10.1111/cpr.12219] [PMID: 26466964]
[30]
Yao M, Zhang J, Gao F, et al. New BMSC-laden gelatin hydrogel formed in situ by dual-enzymatic cross-linking accelerates dermal wound healing. ACS Omega 2019; 4(5): 8334-40.
[http://dx.doi.org/10.1021/acsomega.9b00878] [PMID: 31459921]
[31]
Xiu G, Li X, Yin Y, et al. SDF-1/CXCR4 augments the therapeutic effect of bone marrow mesenchymal stem cells in the treatment of lipo-polysaccharide-induced liver injury by promoting their migration through PI3K/Akt signaling pathway. Cell Transplant 2020; 29: 963689720929992.
[http://dx.doi.org/10.1177/0963689720929992] [PMID: 32452221]
[32]
Zhou X, Liang H, Hu X, et al. BMSC-derived exosomes from congenital polydactyly tissue alleviate osteoarthritis by promoting chondro-cyte proliferation. Cell Death Discov 2020; 6(1): 142.
[http://dx.doi.org/10.1038/s41420-020-00374-z] [PMID: 33303743]
[33]
Zhao J, Ding Y, He R, et al. Dose-effect relationship and molecular mechanism by which BMSC-derived exosomes promote peripheral nerve regeneration after crush injury. Stem Cell Res Ther 2020; 11(1): 360.
[http://dx.doi.org/10.1186/s13287-020-01872-8] [PMID: 32811548]
[34]
Zeng Q, Zhou Y, Liang D, et al. Exosomes secreted from bone fmarrow mesenchymal stem cells attenuate oxygen-glucose depriva-tion/reoxygenation-induced pyroptosis in PC12 cells by promoting AMPK-dependent autophagic flux. Front Cell Neurosci 2020; 14: 182.
[http://dx.doi.org/10.3389/fncel.2020.00182] [PMID: 32765221]
[35]
Mao Q, Liang XL, Zhang CL, Pang YH, Lu YX. LncRNA KLF3-AS1 in human mesenchymal stem cell-derived exosomes ameliorates pyroptosis of cardiomyocytes and myocardial infarction through miR-138-5p/Sirt1 axis. Stem Cell Res Ther 2019; 10(1): 393.
[http://dx.doi.org/10.1186/s13287-019-1522-4] [PMID: 31847890]
[36]
Franke M, Bieber M, Kraft P, Weber ANR, Stoll G, Schuhmann MK. The NLRP3 inflammasome drives inflammation in ische-mia/reperfusion injury after transient middle cerebral artery occlusion in mice. Brain Behav Immun 2021; 92: 223-33.
[http://dx.doi.org/10.1016/j.bbi.2020.12.009] [PMID: 33307174]
[37]
Wang J, Qin Y, Mi X. The protective effects of bone marrow-derived mesenchymal stem cell (BMSC) on LPS-induced acute lung injury via TLR3-mediated IFNs, MAPK and NF-κB signaling pathways. Biomed Pharmacother 2016; 79: 176-87.
[http://dx.doi.org/10.1016/j.biopha.2016.02.037] [PMID: 27044826]
[38]
Xiu G, Sun J, Li X, et al. The role of HMGB1 in BMSC transplantation for treating MODS in rats. Cell Tissue Res 2018; 373(2): 395-406.
[http://dx.doi.org/10.1007/s00441-018-2823-0] [PMID: 29637307]
[39]
Hu J, Yan Q, Shi C, Tian Y, Cao P, Yuan W. BMSC paracrine activity attenuates interleukin-1β-induced inflammation and apoptosis in rat AF cells via inhibiting relative NF-κB signaling and the mitochondrial pathway. Am J Transl Res 2017; 9(1): 79-89.
[PMID: 28123635]
[40]
Liu X, Xu W, Zhang Z, Liu H, Lv LX, Han D, et al. VEGF-transfected BMSC improve the recovery of motor and sensory functions of rats with spinal cord injury. Spine 2020; 45(7): E364-72.
[http://dx.doi.org/10.1097/BRS.0000000000003333] [PMID: 32168135]
[41]
Lu A, Magupalli VG, Ruan J, et al. Unified polymerization mechanism for the assembly of ASC-dependent inflammasomes. Cell 2014; 156(6): 1193-206.
[http://dx.doi.org/10.1016/j.cell.2014.02.008] [PMID: 24630722]
[42]
Zhao LR, Xing RL, Wang PM, et al. NLRP1 and NLRP3 inflammasomes mediate LPS/ATP induced pyroptosis in knee osteoarthritis. Mol Med Rep 2018; 17(4): 5463-9.
[http://dx.doi.org/10.3892/mmr.2018.8520] [PMID: 29393464]
[43]
Cai J, Guan H, Jiao X, et al. NLRP3 inflammasome mediated pyroptosis is involved in cadmium exposure-induced neuroinflammation through the IL-1β/IkB-α-NF-κB-NLRP3 feedback loop in swine. Toxicology 2021; 453(2): 152720.
[http://dx.doi.org/10.1016/j.tox.2021.152720] [PMID: 33592257]

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