Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Oct 15;9(10):4673-4681.
eCollection 2017.

GTS-21 attenuates LPS-induced renal injury via the cholinergic anti-inflammatory pathway in mice

Yang Gao  1 , Kai Kang  2 , Haitao Liu  3 , Weilan Kong  2 , Qiuyuan Han  1 , Xing Zhang  1 , Rui Huang  1 , Jingdong Qu  1 , Hongliang Wang  1 , Sicong Wang  3 , Ruijin Liu  3 , Yansong Liu  3 , Kaijiang Yu  3   4
Affiliations

GTS-21 attenuates LPS-induced renal injury via the cholinergic anti-inflammatory pathway in mice

Yang Gao et al. Am J Transl Res. .

Abstract

This study aimed to investigate the role of GTS-21 in cholinergic anti-inflammatory pathway-mediated protection of LPS-induced septic renal injury in mice. C57BL/6 mice were used to construct septic injury models. The optimal duration of lipopolysaccharide (LPS) treatment was determined using HE staining and TUNEL assay. Mice injected with saline were used as blank control and with LPS (10 mg/kg) as model, which were further treated with α-bungarotoxin (BT-LPS), GTS-21 (GTS-21-LPS) and BT and GTS-21 (BT-GTS-21-LPS). The pathological examinations were performed on HE stained renal tissues, apoptosis was determined using TUNEL assay, mRNA expression of NF-kB p65, Caspase-3, Caspase-8, Bcl-2, Bax, p53 and a7nACh was quantified using qRT-PCR, protein levels of IL-6, IL-1β, TNF-α and phosphorylated STAT3 (p-STAT3) were analyzed using Western blots. HE staining and TUNEL assays showed that the optimal LPS treatment time for renal injury induction was 16 h. Compared with the blank control, mice in LPS group had significantly higher levels of NF-Kb p65, Caspase-3, Caspase-8, Bax, p53, IL-6, IL-1β, TNF-α and p-STAT3, while α7nAChR and Bcl-2 levels were decreased significantly (P < 0.01); GTS-21 and BT significantly increased the expression of NF-Kb p65, Caspase-3, Caspase-8, Bax, p53, IL-6, IL-1β, TNF-α and p-STAT3, while α7nAChR and Bcl-2 levels were decreased significantly (P < 0.01). It is concluded that GTS-21 can effective alleviate the renal injury, while α7nAChR-specific blocker BT is antagonistic against the anti-inflammatory effect of GTS-21 on sepsis in mice.

Keywords: Cholinergic anti-inflammatory pathway; GTS-21; gene expression; renal injury; sepsis.

PubMed Disclaimer

Conflict of interest statement

None.

Figures

Figure 1
Figure 1
HE staining and TUNEL results of renal tissues following LPS treatments for different times (200×). A. HE staining, B. Microphotos of TUNEL assay, C. Number of apoptotic cells.
Figure 2
Figure 2
HE staining results of renal tissues following GTS-21, BT and LPS treatments (200×).
Figure 3
Figure 3
TUNEL results of renal tissues GTS-21, BT and LPS treatments. A. Microphotos of TUNEL assay, B. Number of apoptotic cells.
Figure 4
Figure 4
Relative mRNA level of NF-kB, α7nAChR, Caspase-3, Caspase-8, Bcl-2, Bax and p53 mRNA in renal tissue following GTS-21, BT and LPS treatments. A. NF-kB and α7nAChR expression; B. Caspase-3, Caspase-8, Bcl-2, Bax and p53 expression. *** denote P < 0.001 vs control.
Figure 5
Figure 5
Expression of IL-6, IL-1β, TNF-α and p-STAT3 proteins in renal tissue following GTS-21, BT and LPS treatments. Upper panel: representative Western blots, lower panel: relative protein levels. *** denote P < 0.01 vs control.
See this image and copyright information in PMC

References

    1. Angeli P, Gines P, Wong F, Bernardi M, Boyer TD, Gerbes A, Moreau R, Jalan R, Sarin SK, Piano S, Moore K, Lee SS, Durand F, Salerno F, Caraceni P, Kim WR, Arroyo V, Garcia-Tsao G International Club of Ascites. Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites. Gut. 2015;64:531–537. - PubMed
    1. Hoste EA, Bagshaw SM, Bellomo R, Cely CM, Colman R, Cruz DN, Edipidis K, Forni LG, Gomersall CD, Govil D, Honore PM, Joannes-Boyau O, Joannidis M, Korhonen AM, Lavrentieva A, Mehta RL, Palevsky P, Roessler E, Ronco C, Uchino S, Vazquez JA, Vidal Andrade E, Webb S, Kellum JA. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med. 2015;41:1411–1423. - PubMed
    1. Mao Y, Tokudome T, Kishimoto I, Otani K, Nishimura H, Yamaguchi O, Otsu K, Miyazato M, Kangawa K. Endogenous ghrelin attenuates pressure overload-induced cardiac hypertrophy via a cholinergic anti-inflammatory pathway. Hypertension. 2015;65:1238–1244. - PubMed
    1. Payolla TB, Lemes SF, de Fante T, Reginato A, Mendes da Silva C, de Oliveira Micheletti T, Rodrigues HG, Torsoni AS, Milanski M, Torsoni MA. High-fat diet during pregnancy and lactation impairs the cholinergic anti-inflammatory pathway in the liver and white adipose tissue of mouse offspring. Mol Cell Endocrinol. 2016;422:192–202. - PubMed
    1. Liu F, Li Y, Jiang R, Nie C, Zeng Z, Zhao N, Huang C, Shao Q, Ding C, Qing C, Xia L, Zeng E, Qian K. miR-132 inhibits lipopolysaccharide-induced inflammation in alveolar macrophages by the cholinergic anti-inflammatory pathway. Exp Lung Res. 2015;41:261–269. - PubMed

LinkOut - more resources