Transcriptome Analysis Revealed Inflammation Is Involved in the Impairment of Human Umbilical Vein Endothelial Cells Induced by Post-hemorrhagic Shock Mesenteric Lymph.

Abstract

Vascular endothelial injury caused by post-hemorrhagic shock mesenteric lymph (PHSML) return is an important manifestation during refractory hemorrhagic shock. Using human umbilical vein endothelial cells (HUVECs) and transcriptome analysis, this study sought to investigate the molecular mechanism underlying the adverse effect of PHSML on vascular endothelium. Post-hemorrhagic shock mesenteric lymph was collected from male rats after they underwent hemorrhagic shock and following resuscitation, while normal mesenteric lymph (NML) was harvested from sham rats. Human umbilical vein endothelial cells were incubated with the culture medium containing either 10% phosphate buffered saline (Control), NML, or PHSML for 3 h, and then were harvested for RNA sequencing. In comparison with NML treated cells, 37 genes were differentially expressed in PHSML-treated HUVECs, including 32 upregulated genes and five downregulated genes. These differentially expressed genes were mainly enriched in inflammatory pathways, including signaling pathways for activation of the NOD-like receptors, NF-κB, and TNF. Furthermore, we found that C-C motif chemokine ligand 2 (CCL2) was increased significantly after PHSML treatment, and Bindarit, a CCL2 production inhibitor, attenuated the damage of HUVECs induced by PHSML. The results provide molecular evidence on vascular endothelium damage caused by PHSML. C-C motif chemokine ligand 2 might represent a new target for reducing vascular injury after severe hemorrhagic shock.

• Authors: Qi Wang, Zhen-Fen Chi, Di Wei, Zhen-Ao Zhao, Hong Zhang, Li-Min Zhang, Yan-Xu Liu, An-Ling Kang, Meng Zhao, Peng Wang, Ling-Hu Nie, Chun-Yu Niu, Zi-Gang Zhao
• Journal: Frontiers in immunology (Front Immunol) Vol. 11 Pg. 1717 ( 2020) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 33013823 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Wang, Chi, Wei, Zhao, Zhang, Zhang, Liu, Kang, Zhao, Wang, Nie, Niu and Zhao.

Chemical References

• Anti-Inflammatory Agents
• Indazoles
• Propionates
• bindarit

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Cells, Cultured
• Disease Models, Animal
• Gene Expression Profiling
• Gene Regulatory Networks
• Human Umbilical Vein Endothelial Cells (drug effects, metabolism, pathology)
• Humans
• Indazoles (pharmacology)
• Inflammation (etiology, genetics, metabolism, pathology)
• Lymph (metabolism)
• Lymphatic System (metabolism)
• Male
• Mesentery
• Propionates (pharmacology)
• Rats, Wistar
• Shock, Hemorrhagic (complications, metabolism)
• Signal Transduction
• Transcriptome