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GAB1 attenuates lipopolysaccharide‑mediated endothelial dysfunction via regulation of SOCS3

  • Authors:
    • Guangdong Ren
    • Ran Liu
    • Huiqiang Mai
    • Gang Yin
    • Fulai Ding
    • Chunmei Wang
    • Shuxin Chen
    • Xianqi Lan
  • View Affiliations / Copyright

    Affiliations: Emergency Department, Zhongshan City People's Hospital, Zhongshan, Guangdong 528403, P.R. China
    Copyright: © Ren et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 400
    |
    Published online on: August 14, 2024
       https://doi.org/10.3892/etm.2024.12689
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Abstract

Endothelial dysfunction is a crucial pathogenetic mechanism for sepsis. GRB2‑associated binder 1 (GAB1) alleviates sepsis‑induced multi‑organ damage; however, to the best of our knowledge, its function in endothelial dysfunction in sepsis remains unclear. HUVECs were induced by lipopolysaccharide (LPS) to simulate endothelial cell injury under sepsis. Cell transfection was conducted to achieve GAB1 overexpression or suppressor of cytokine signaling 3 (SOCS3) knockdown. The expression levels of GAB1 and SOCS3 were detected by reverse transcription‑quantitative PCR and western blotting. Cell viability, apoptosis and migration were assessed using Cell Counting Kit‑8, TUNEL and wound healing assays, respectively. The production of cytokines and nitric oxide (NO) was detected using commercial kits. The interaction between GAB1 and SOCS3 was confirmed using a co‑immunoprecipitation assay. GAB1 was downregulated in LPS‑induced HUVECs. However, GAB1 overexpression significantly mitigated LPS‑induced cell viability decrease and apoptosis in HUVECs, accompanied by upregulation of Bcl2 expression, and downregulation of Bax and cleaved caspase‑3 expression. GAB1 also inhibited the production of pro‑inflammatory cytokines and increased NO level, increased the levels of endothelial NO synthase (eNOS) and phosphorylated (p)‑eNOS, and promoted migration in LPS‑induced HUVECs. However, SOCS3 knockdown partially weakened the effects of GAB1 overexpression on cell viability, apoptosis, inflammation, p‑eNOS, eNOS expression and NO levels in LPS‑induced HUVECs. In addition, GAB1 and SOCS3 regulated Janus kinase 2 (JAK2)/STAT3 signaling in LPS‑induced HUVECs. In conclusion, GAB1 exerted a protective effect against LPS‑induced endothelial cell apoptosis, inflammation and dysfunction by modulating the SOCS3/JAK2/STAT3 signaling pathway.
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Copy and paste a formatted citation
Spandidos Publications style
Ren G, Liu R, Mai H, Yin G, Ding F, Wang C, Chen S and Lan X: GAB1 attenuates lipopolysaccharide‑mediated endothelial dysfunction via regulation of SOCS3. Exp Ther Med 28: 400, 2024.
APA
Ren, G., Liu, R., Mai, H., Yin, G., Ding, F., Wang, C. ... Lan, X. (2024). GAB1 attenuates lipopolysaccharide‑mediated endothelial dysfunction via regulation of SOCS3. Experimental and Therapeutic Medicine, 28, 400. https://doi.org/10.3892/etm.2024.12689
MLA
Ren, G., Liu, R., Mai, H., Yin, G., Ding, F., Wang, C., Chen, S., Lan, X."GAB1 attenuates lipopolysaccharide‑mediated endothelial dysfunction via regulation of SOCS3". Experimental and Therapeutic Medicine 28.4 (2024): 400.
Chicago
Ren, G., Liu, R., Mai, H., Yin, G., Ding, F., Wang, C., Chen, S., Lan, X."GAB1 attenuates lipopolysaccharide‑mediated endothelial dysfunction via regulation of SOCS3". Experimental and Therapeutic Medicine 28, no. 4 (2024): 400. https://doi.org/10.3892/etm.2024.12689
Copy and paste a formatted citation
x
Spandidos Publications style
Ren G, Liu R, Mai H, Yin G, Ding F, Wang C, Chen S and Lan X: GAB1 attenuates lipopolysaccharide‑mediated endothelial dysfunction via regulation of SOCS3. Exp Ther Med 28: 400, 2024.
APA
Ren, G., Liu, R., Mai, H., Yin, G., Ding, F., Wang, C. ... Lan, X. (2024). GAB1 attenuates lipopolysaccharide‑mediated endothelial dysfunction via regulation of SOCS3. Experimental and Therapeutic Medicine, 28, 400. https://doi.org/10.3892/etm.2024.12689
MLA
Ren, G., Liu, R., Mai, H., Yin, G., Ding, F., Wang, C., Chen, S., Lan, X."GAB1 attenuates lipopolysaccharide‑mediated endothelial dysfunction via regulation of SOCS3". Experimental and Therapeutic Medicine 28.4 (2024): 400.
Chicago
Ren, G., Liu, R., Mai, H., Yin, G., Ding, F., Wang, C., Chen, S., Lan, X."GAB1 attenuates lipopolysaccharide‑mediated endothelial dysfunction via regulation of SOCS3". Experimental and Therapeutic Medicine 28, no. 4 (2024): 400. https://doi.org/10.3892/etm.2024.12689
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