HPMC Inflammatory Response under HMGB1-MAPK Signaling Pathway in High Glucose Environment

Abstract

Objective: The study aimed to explore the role and molecular mechanism of High Mobility Group B 1 (HMGB1) on inflammatory response of Peritoneal Mesothelial Cells (PMC) mediated by high concentration glucose environment. Methods: The human peritoneal mesothelial cell (HPMC) line Human PMC strains (HMrSV5) was used as a research object and cultured in vitro. Enzyme-linked immuno sorbent assay (ELISA), immunofluorescence, and real-time polymerase chain reaction (PCR) were performed after grouping, and small interfering RNA (siRNA) gene silencing technique was used to analyze the effect of HGMB1 expression inhibition on the release of inflammatory factors in a high glucose environment. Finally, the effects of HMGB1 on monocyte chemoattractant protein 1 (MCP-1) and Interleukin-8 (IL-8) expression were investigated using inhibitors of key factors of the mitogen-activated protein kinase (MAPK) pathway. Results: The content of HMGB1 in the supernatant of group A was significantly higher than that in group B and group C (p < 0.05), suggesting that high glucose can promote the transfer of HMGB1 from intracellular to extracellular space in PMC. With the increase of glucose concentration and incubation time, the expression of extracellular HMGB1 significantly increased. After silencing HMGB1 expression, the content of inflammatory factors in PMC significantly decreased. Conclusions: HMGB1 can directly promote the release of inflammatory factors, especially inflammation factor MCP-1. And the path of inflammatory mechanism of HMGB1 was the HMGB1-MAPK signaling pathway.