Open Access

Adipose‑derived mesenchymal stem cell‑derived HCAR1 regulates immune response in the attenuation of sepsis

  • Authors:
    • Hongyan Wang
    • Pengfei Xuan
    • Hongjun Tian
    • Xinyu Hao
    • Jingping Yang
    • Xiyuan Xu
    • Lixia Qiao
  • View Affiliations

  • Published online on: July 15, 2022     https://doi.org/10.3892/mmr.2022.12795
  • Article Number: 279
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Sepsis serves as a leading cause of admission to and death of patients in the intensive care unit (ICU) and is described as a systemic inflammatory response syndrome caused by abnormal host response to infection. Adipose‑derived mesenchymal stem cells (ADSCs) have exhibited reliable and promising clinical application potential in multiple disorders. However, the function and the mechanism of ADSCs in sepsis remain elusive. In the present study, the crucial inhibitory effect of ADSC‑derived hydroxy‑carboxylic acid receptor 1 (HCAR1) on sepsis was identified. Reverse transcription quantitative‑PCR determined that the mRNA expression of HCAR1 was reduced while the mRNA expression of Toll‑like receptor 4 (TLR4), major histocompatibility complex class II (MHC II), NOD‑like receptor family pyrin domain containing 3 (NLRP3), and the levels of interleukin‑1β (IL‑1β), tumor necrosis factor‑α (TNF‑α), interleukin‑10 (IL‑10), and interleukin‑18 (IL‑18) were enhanced in the peripheral blood of patients with sepsis. The expression of HCAR1 was negatively correlated with TLR4 (r=‑0.666), MHC II (r=‑0.587), and NLRP3 (r=‑0.621) expression and the expression of TLR4 was positively correlated with NLRP3 (r=0.641), IL‑1β (r=0.666), TNF‑α (r=0.606), and IL‑18 (r=0.624) levels in the samples. Receiver operating characteristic (ROC) curve analysis revealed that the area under the ROC curve (AUC) of HCAR1, TLR4, MHC II and NLRP3 mRNA expression was 0.830, 0.853, 0.735 and 0.945, respectively, in which NLRP3 exhibited the highest diagnostic value, and the AUC values of IL‑1β, IL‑18, TNF‑α, and IL‑10 were 0.751, 0.841, 0.924 and 0.729, respectively, in which TNF‑α exhibited the highest diagnostic value. A sepsis rat model was established by injecting lipopolysaccharide (LPS) and the rats were randomly divided into 5 groups, including a normal control group (NC group; n=6), a sepsis model group (LPS group; n=6), an ADSC transplantation group (L + M group; n=6), a combined HCAR1 receptor agonist group [L + HCAR1 inducer (Gi) + M group; n=6], and a combined HCAR1 receptor inhibitor group [L + HCAR1 blocker (Gk) + M group; n=6]. Hematoxylin and eosin staining determined that ADSCs attenuated the lung injury of septic rats and ADSC‑derived HCAR1 enhanced the effect of ADSCs. The expression of HCAR1, TLR4, MHC II, NLRP3, IL‑1β, IL‑18 and TNF‑α levels were suppressed by ADSCs and the effect was further induced by ADSC‑derived HCAR1. However, ADSC‑derived HCAR1 induced the levels of anti‑inflammatory factor IL‑10. The negative correlation of HCAR1 expression with TLR4, MHC II, and NLRP3 expression in the peripheral blood and lung tissues of the rats was then identified. It is thus concluded that ADSC‑derived HCAR1 regulates immune response in the attenuation of sepsis. ADSC‑derived HCAR1 may be a promising therapeutic strategy for sepsis.
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September-2022
Volume 26 Issue 3

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Spandidos Publications style
Wang H, Xuan P, Tian H, Hao X, Yang J, Xu X and Qiao L: Adipose‑derived mesenchymal stem cell‑derived HCAR1 regulates immune response in the attenuation of sepsis. Mol Med Rep 26: 279, 2022.
APA
Wang, H., Xuan, P., Tian, H., Hao, X., Yang, J., Xu, X., & Qiao, L. (2022). Adipose‑derived mesenchymal stem cell‑derived HCAR1 regulates immune response in the attenuation of sepsis. Molecular Medicine Reports, 26, 279. https://doi.org/10.3892/mmr.2022.12795
MLA
Wang, H., Xuan, P., Tian, H., Hao, X., Yang, J., Xu, X., Qiao, L."Adipose‑derived mesenchymal stem cell‑derived HCAR1 regulates immune response in the attenuation of sepsis". Molecular Medicine Reports 26.3 (2022): 279.
Chicago
Wang, H., Xuan, P., Tian, H., Hao, X., Yang, J., Xu, X., Qiao, L."Adipose‑derived mesenchymal stem cell‑derived HCAR1 regulates immune response in the attenuation of sepsis". Molecular Medicine Reports 26, no. 3 (2022): 279. https://doi.org/10.3892/mmr.2022.12795