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. 2019 Dec 20;39(12):BSR20192368.
doi: 10.1042/BSR20192368.

Gal-3 is a potential biomarker for spinal cord injury and Gal-3 deficiency attenuates neuroinflammation through ROS/TXNIP/NLRP3 signaling pathway

Zhouliang Ren  1 , Weidong Liang  1 , Jun Sheng  1 , Chuanhui Xun  1 , Tao Xu  1 , Rui Cao  1 , Weibin Sheng  1
Affiliations

Gal-3 is a potential biomarker for spinal cord injury and Gal-3 deficiency attenuates neuroinflammation through ROS/TXNIP/NLRP3 signaling pathway

Zhouliang Ren et al. Biosci Rep. .

Abstract

Spinal cord injury (SCI) often occurs in young and middle-aged population. The present study aimed to clarify the function of Galectin-3 (Gal-3) in neuroinflammation of SCI. Sprague-Dawley (SD) rat models with SCI were established in vivo. PC12 cell model in vitro was induced by lipopolysaccharide (LPS). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Gene chip were used to analyze the expression levels of genes in the signaling pathway. Histological assessment, ELISA and Western blotting were conducted to evaluate the effects of Gal-3 upon the SCI model. In the in vivo SD rat model, Gal-3 expression level was up-regulated. The inhibition of Gal-3 attenuated the neuroinflammation in SCI model. The inhibition of Gal-3 could also mitigate the neuroinflammation and reactive oxygen species (ROS) in in vitro model. ROS reduced the effect of Gal-3 on oxidative stress in in vitro model. Down-regulating the content of TXNIP decreased the effect of Gal-3 on neuroinflammation in in vitro model. Suppressing the level of NLRP3 could weaken the effect of Gal-3 on neuroinflammation in in vitro model. Our data highlight that the Gal-3 plays a vital role in regulating the severity of neuroinflammation of SCI by enhancing the activation of ROS/TXNIP/NLRP3 signaling pathway. In addition, inflammasome/IL-1β production probably acts as the therapeutic target in SCI.

Keywords: Gal-3; NLRP3; ROS; Spinal cord injury; TXNIP.

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Conflict of interest statement

The present study was approved by the Scientific Review Committee and the Institutional Review Board of the First Affiliated Hospital of Xinjiang Medical University.

The authors declare that there are no competing interests associated with the manuscript.

Figures

Figure 1
Figure 1. Gal-3 expression in SCI model
BBB score (A), water content of spinal cord (B), HE staining (C), p65 (D), TNF-α (E), IL-1β (F), IL-6 (G), MDA (H), SOD (I), CAT (J) and GSH-PX levels (K), Gal-3 mRNA expression (L) in SCI model. Control, control sham group; SCI, SCI model group. **P<0.01 compared with control group.
Figure 2
Figure 2. The inhibition of Gal-3 attenuates neuroinflammation in SCI model
BBB score (A), water content of spinal cord (B), HE staining (C), p65 (D), TNF-α (E), IL-1β (F), IL-6 (G), MDA (H), SOD (I), CAT (J) and GSH-PX levels (K), Gal-3 mRNA expression (L) in SCI model. Control, control sham group; SCI, SCI model group; SCI+GB1107, SCI model by GB1107 group. **P<0.01 compared with control group, ##P<0.01 compared with SCI model group.
Figure 3
Figure 3. Gal-3 target spot TXNIP/NLRP3
Gene chip (A), analysis chart (B), network signal diagram (C), structural formula of Gal-3 (D), Gal-3 induced Gal-3, TXNIP and NLRP3 protein expressions in in vitro model of SCI (E–H), GB1107 suppressed Gal-3, TXNIP and NLRP3 protein expressions in rat model of SCI (I–L). Negative, negative mimic group; Gal-3, overexpression of Gal-3 group; Control, control sham group; SCI, SCI model group; SCI+GB1107, SCI model by GB1107 group. **P<0.01 compared with negative or control group, ##P<0.01 compared with SCI model group.
Figure 4
Figure 4. The inhibition of Gal-3 attenuates neuroinflammation and ROS in in vitro model
Gal-3, TXNIP and NLRP3 protein expressions (A–D), IL-1β levels (E), ROS levels (F,G), MDA (H), SOD (I), CAT (J) and GSH-PX levels (K), Gal-3 protein expression (immunofluorescent staining, (L). Control, control group; LPS, SCI model group; LPS+si-Gal-3, SCI model by si-Gal-3 group. **P<0.01 compared with control group, ##P<0.01 compared with SCI model group.
Figure 5
Figure 5. ROS regulates the effects of Gal-3 on oxidative stress in vitro model
ROS levels (A,B), MDA (C), SOD (D), CAT (E) and GSH-PX levels (F) in vitro model by overexpression of ROS; ROS levels (G,H), MDA (I), SOD (J), CAT (K) and GSH-PX levels (L) in vitro model by ROS inhibitor. Control, control group; LPS, SCI model group; LPS+si-Gal-3, SCI model by si-Gal-3 group; LPS+si-Gal-3+H2O2, SCI model by si-Gal-3 and H2O2 group; LPS+ROS inhibitor, SCI model by ROS inhibitor group; LPS+ROS inhibitor+Gal-3, SCI model by ROS inhibitor and Gal-3 group. **P<0.01 compared with control group, ##P<0.01 compared with SCI model group; ***P<0.01 compared with LPS+ROS inhibitor or LPS+si-Gal-3 group.
Figure 6
Figure 6. ROS regulates the effects of Gal-3 on neuroinflammation in vitro model
Expression of TXNIP and NLRP3 proteins (A–C), IL-1β levels (D) by overexpression of ROS; TXNIP and NLRP3 protein expressions (E–G), IL-1β levels (H) by ROS inhibitor. Control, control group; LPS, SCI model group; LPS+si-Gal-3, SCI model by si-Gal-3 group; LPS+si-Gal-3+H2O2, SCI model by si-Gal-3 and H2O2 group; LPS+ROS inhibitor, SCI model by ROS inhibitor group; LPS+ROS inhibitor+Gal-3, SCI model by ROS inhibitor and Gal-3 group. **P<0.01 compared with control group, ##P<0.01 compared with SCI model group; ***P<0.01 compared with LPS+ROS inhibitor or LPS+si-Gal-3 group.
Figure 7
Figure 7. The inhibition of TXNIP reduced the effect of Gal-3 on neuroinflammation in vitro model
TXNIP and NLRP3 protein expressions (A–C) by overexpression of TXNIP; TXNIP and NLRP3 protein expressions (D–F) by down-regulation of TXNIP; IL-1β levels (G) by overexpression of TXNIP; IL-1β levels (H) by down-regulation of TXNIP. Control, control group; LPS, SCI model group; LPS+si-TXNIP, SCI model by si-TXNIP group; LPS+si-TXNIP+Gal-3, SCI model by si-TXNIP+Gal-3 group; LPS+si-Gal-3, SCI model by i-Gal-3 group; LPS+si-Gal-3+TXNIP, SCI model by si-Gal-3+TXNIP group. **P<0.01 compared with control group, ##P<0.01 compared with SCI model group; ***P<0.01 compared with LPS+si-TXNIP and LPS+si-Gal-3 group.
Figure 8
Figure 8. The inhibition of NLRP3 reduced the effect of Gal-3 on neuroinflammation in vitro model
NLRP3 protein expressions (A,B), IL-1β levels (C) by overexpression of NLRP3; NLRP3 protein expressions (D,E), IL-1β levels (F) by down-regulation of NLRP3; Control, control group; LPS, SCI model group; LPS+si-NLRP3, SCI model by si-NLRP3 group; LPS+si-NLRP3+Gal-3, SCI model by si-NLRP3+Gal-3 group; LPS+si-Gal-3, SCI model by i-Gal-3 group; LPS+si-Gal-3+ NLRP3, SCI model by si-Gal-3+ NLRP3 group. **P<0.01 compared with control group, ##P<0.01 compared with SCI model group; ***P<0.01 compared with LPS+si-NLRP3 and LPS+si-Gal-3 groups.
Figure 9
Figure 9. Gal-3 acts as a potential biomarker for SCI and Gal-3 deficiency, attenuates neuroinflammation through ROS/TXNIP/NLRP3 signaling pathway
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