HRGP protects liver IRI via mir8114. undefined

Histidine-rich glycoprotein (HRGP) is a multifunctional protein that can interact with a variety of immune cells, and recent articles have reported the protective effect of HRGP against hepatic ischemia-reperfusion injury (IRI) by affecting neutrophil infiltration. Macrophages are important initiating and participating cells in hepatic ischemia-reperfusion injury, and the role of HRGP in macrophages during IRI remains unclear. By RNA-sequencing analysis of WT and HRGP knockout (HRGP-KO) mice before and after liver IRI, we found that the expression of mir-8114 was significantly increased during liver IRI, and HRGP-KO further enhanced the expression of mir-8114 Express. During IRI, endoplasmic reticulum (ER) stress-related pathways were activated, whereas HRGP-KO mainly affected pathways related to inflammatory cell infiltration and cytokine secretion (especially TNF-α). Further studies on bone marrow-derived macrophages (BMDMs) showed that HRGP upregulates apoptosis-related pathways by inhibiting mir-8114, whereas ER stress pathways are not affected by HRGP treatment. Pretreatment with antmir-8114 significantly reduced hepatic IRI with less macrophage apoptosis. Collectively, our data elucidate HRGP as a key molecule and its mechanism in promoting apoptotic pathway in macrophages. The regulatory relationship between HRGP and mir8114 can provide new research ideas for HRGP-induced apoptosis of other immune cells, and provide new targets for the treatment of hepatic IRI.