| Autor: |
Zhusheng Feng, Yingnan Fan, Jiangang Xie, Shanshou Liu, Chujun Duan, Qianmei Wang, Yuqin Ye, Wen Yin |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Biochemical and biophysical research communications. 637 |
| ISSN: |
1090-2104 |
| Popis: |
Hemorrhagic shock (HS) is a global life-threatening matter that causes massive mortality annually worldwide. Syndecan-1 (SDC1) is an important predictor and evaluation index for HS, but its mechanism involved in the HS development remain unclear. HS mice model and human umbilical vein endothelial cells (HUVECs) under hypoxia were applied to explore the relationship of SDC1 with HIF-1α and NLRP3 inflammasome in vascular ECs under HS. Transcriptome sequencing of isolated vascular ECs were conduct to search for hub genes. Dual luciferase assay was adopted to prove the binding effects of the HIF-1α on SDC1 promoter in HUVECs. Molecular expression was evaluated through routine experiments. Here, HS led to aggravated lung injury and inflammatory response with the shedding of SDC1 on the lung vascular ECs in mice. Circulatory SDC1 and proinflammatory cytokines were significantly increased after HS. HIF-1α and IL-1β were identified as hub genes in vascular ECs of HS mice. Meanwhile, HIF-1α-mediaed hypoxia and IL-1β-involved NLRP3 inflammasome pathways were activated following HS. The transcriptional factor HIF-1α promoted the expression of SDC1 through binding to the SDC1 promoter. SDC1 had an inhibitory effect on the NLRP3 inflammasome activity. An exogenous increase of HIF-1α upregulated SDC1 and restrained the activation of the NLRP3 inflammasome under hypoxia, while further interference of SDC1 weakened this effect. Hence, SDC1 is an intermediate connecting HIF-1α and NLRP3 inflammasome in the vascular ECs under hypoxia. HIF-1α promotes the expression of SDC1 and inhibits the NLRP3 inflammasome pathway in vascular ECs under HS. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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