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Cell and Tissue Research

, Volume 373, Issue 2, pp 395–406 | Cite as

The role of HMGB1 in BMSC transplantation for treating MODS in rats

  • Guanghui Xiu
  • Jie Sun
  • Xiuling Li
  • Hua Jin
  • Yichao Zhu
  • Xia Zhou
  • Ping Liu
  • Xinghua Pan
  • Jian Li
  • Bin Ling
Regular Article
  • 106 Downloads

Abstract

The effect of bone marrow mesenchymal stem cells (BMSCs) in treatment for multiple organ dysfunction syndrome (MODS) remains unknown and the mechanism is still unclear. Therefore, the goal of this study is to investigate the effects of intracellular high mobility group box 1 protein (HMGB1) on BMSCs treating for MODS. The rats were given 15% blood loss plus 1 mg/kg lipopolysaccharide (LPS) via lower extremity superficial venous, then randomly allocated into four groups: sham group, MODS group, MODS plus BMSC group, MODS plus ethyl pyruvate (EP) group, MODS plus BMSCs plus EP group. Twenty-four hours later, rats in groups were sacrificed and then the blood and tissues were collected to evaluate the changes of tissue histopathology, cell apoptosis, inflammation level and organ function. The HGMB1 expression was monitored by RT-qPCR and Western blot. The expression of RAGE/TLR2/TLR4 and NF-κB at the protein levels was also assessed. BMSCs and/or EP exhibits an outstanding protective effect against LPS-induced histopathological injury by improving cell apoptosis, inflammatory response and the organ dysfunction but no effect on BMSC homing to the injury site. Moreover, BMSCs and/or EP inhibited LPS-induced upregulation of HMGB1, RAGE, TLR2 and TLR4 expression at protein levels and compromised p65 phosphorylation in the rat model of MODS. These findings suggest that HMGB1 is involved in BMSC treatment for MODS, through regulation of the TLR2, TLR4-mediated NF-κB signal pathway. It suggests that HMGB1 is an attractive potential target for the development of new therapeutic strategies for MODS.

Keywords

MODS BMSC HMGB1 Lipopolysaccharide NF-κB signal pathway 

Notes

Funding information

This work was supported by the Natural Science Foundation of China (81360289) and the Applied Basic Research of Yunnan Province (Associated Special Program of Kunming Medical University) (2012FB076, 2015FB079, 2017FE468(1180)).

Compliance with ethical standards

Rat care was in full compliance with the Guide for the Care and Use of Laboratory Animals and the use of laboratory animals in the research and all studies were approved by the Animal Ethical Committee of Kunming Medical University.

Conflict of interest

The authors declare that they have no conflicts of interest.

Supplementary material

441_2018_2823_MOESM1_ESM.jpg (72 kb)
ESM 1 The identify of biomarkers in BMSCs Expression of CD90 + CD34 (B), CD44 + CD45 (C), and control by cultured cells was evaluated by flow cytometric analysis using anti-CD34, anti-CD44, anti-CD45, and anti-CD90 antibodies. Control isotype antibody is plotted in (A). Cultured cells were confirmed as BM-MSCs by their appearance in culture and by the CD44+CD90+CD34-CD45- phenotype (JPEG 72.3 kb)
441_2018_2823_MOESM1_ESM.tif (918 kb)
High resolution (TIF 918 kb)
441_2018_2823_MOESM2_ESM.jpg (233 kb)
ESM 2 The beneficial effects of BMSCs on MODS treatment Different organ morphological changes in intestine (A and B), liver (C), kidney (D), lung (E), and spleen (F) of SD rats 24 hours after LPS-administration (1mg/kg i.v.) (40× magnification). (G) Histopathological analysis of the heart, lung, intestine, liver and kidney. M, MODS; N, Normal (JPEG 233 kb)
441_2018_2823_MOESM2_ESM.tif (6.9 mb)
High resolution (TIF 6.90 mb)
441_2018_2823_MOESM3_ESM.jpg (292 kb)
ESM 3 BMSCs homed to damaged tissues Immunofluorescence staining of the heart (A), liver (B), spleen (C), lung (D), kidney (E), intestine (F), brain (G) and quadriceps (H) of SD rats 3 days after BMSCs transplantation. (JPEG 219 kb)
441_2018_2823_MOESM3_ESM.tif (7.3 mb)
High resolution (TIF 7.30 mb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Guanghui Xiu
    • 1
  • Jie Sun
    • 1
  • Xiuling Li
    • 2
  • Hua Jin
    • 3
  • Yichao Zhu
    • 4
  • Xia Zhou
    • 1
  • Ping Liu
    • 1
  • Xinghua Pan
    • 5
  • Jian Li
    • 6
  • Bin Ling
    • 1
  1. 1.Department of ICUThe Second People’s Hospital of Yunnan ProvinceKunmingChina
  2. 2.Department of ObstetricsThe First People’s Hospital of Yunnan ProvinceKunmingChina
  3. 3.Department of AnesthesiologyThe First People’s Hospital of Yunnan ProvinceKunmingChina
  4. 4.Department of AnesthesiologyThe affiliated Hospital of Binzhou Medical UniversityBinzhouChina
  5. 5.Stem Cell Engineering Laboratory of Yunnan Province, Kunming General Hospital, Chengdu Military CommandKunmingChina
  6. 6.Kunming Biological Diversity Regional Center of Instruments, Kunming Institute of ZoologyChinese Academy of SciencesKunmingChina

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