Fig. 4: iRhom2 controls inflammation and HMGB1 secretion in a TACE-independent manner during IRI.

A Schematic representation of the modified in vitro IRI protocol established for the study. B Volcano plot showing the -Log10 of p-values versus the log2 of protein ratio between iRhom2 KD and NTC KD macrophages at 4 h reperfusion (n = 4). Statistical significance was set at p < 0.05 and log2 (fold change) >0.5 was represented as black dashed lines. Secreted proteins significantly reduced in iRhom2 KD macrophages are displayed as red-filled dots, unchanged and less abundant proteins as transparent gray dots. C Top 5 functional GOBP for proteins decreased in iRhom2 KD macrophages secretome analysis. D ELISA assay showing HMGB1 protein quantification in the conditioned medium (CM) of reperfused NTC KD, iRhom2KD, TACE KD and Marimastat-treated M1 primary macrophages at different IRI time points (n = 3). D Two-way ANOVA with Sidak correction (**p < 0.01; ****p < 0.001; ns not significant). Created in BioRender. Zito, G. (2025) https://BioRender.com/1ih7lgh.