Endocrine Abstracts

JOINT2661

Introduction: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant public health concern, with macrophage phenotypes implicated in its progression. Although Extensive Inflammation-Suppressing Circular RNA (CiR-EIS) has been implicated in inflammation regulation, its role in macrophage polarization within the context of MASH remains unexplored. This study aimed to clarify the effect of CiR-EIS on macrophage polarization in MASH.

Methods: Immunofluorescence-fluorescence in situ hybridization was used to evaluate the localization of CiR-EIS in human liver sections. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of CiR-EIS in serum and cells. Flow cytometry was employed to evaluate macrophage polarization. Enzyme linked immunosorbent assay (ELISA) was used to detect the content of inflammatory factors. Dual luciferase reporter assay was used to identify the downstream targets of CiR-EIS.

Results: CiR-EIS was downregulated in patients with MASH and localized in liver macrophages. Compared with the control group, the expression of CiR-EIS in M1 macrophages was decreased. Overexpression of CiR-EIS significantly inhibited M1 macrophage markers CD86, interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) while enhancing M2 macrophage markers CD163 and CD206. MiR-548 was screened and identified as a downstream target of CiR-EIS. Up-regulation of miR-548 promoted M1 macrophage polarization and reduced M2 macrophage polarization. CiR-EIS had a region that binds to miR-548. CiR-EIS sponged miR-548 to regulate the polarization of macrophages. In addition, the serum CiR-EIS content of MASH patients was lower than that of healthy people. The content of CiR-EIS in serum was negatively correlated with the content of alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

Conclusions: CiR-EIS regulates macrophage polarization by sponging miR-548, thereby ameliorating MASH. It demonstrates potential as a diagnostic marker and therapeutic target for MASH.