DICAM deficiency exacerbates cisplatin-induced acute kidney injury through enhanced oxidative stress, inflammation, and tubular cell death

Cisplatin-induced acute kidney injury (AKI) is characterized by oxidative stress, inflammation, and tubular cell death, yet endogenous mechanisms regulating these processes remain incompletely understood. DICAM (dual immunoglobulin domain-containing cell adhesion molecule, also known as MXRA8) has been implicated in renal tubular injury responses, but its role in AKI remains unclear. We investigated the function of DICAM using siRNA-mediated knockdown in HK-2 cells and DICAM knockout mice with cisplatin-induced AKI. Renal function, histological injury, oxidative stress, mitogen-activated protein kinase (MAPK) signaling, inflammatory responses, apoptosis, early profibrotic changes, and adhesion-related molecule expression were comprehensively assessed. DICAM expression was significantly upregulated following cisplatin exposure in HK-2 cells. DICAM deficiency exacerbated renal dysfunction and tubular injury after cisplatin administration. DICAM deficiency increased reactive oxygen species (ROS) accumulation and NOX4 expression, along with changes in selected MAPK signaling components. These findings were accompanied by increased inflammatory responses, macrophage infiltration, tubular apoptosis, and early profibrotic changes. DICAM deficiency also altered adhesion-related molecules, including increased integrin β1 and decreased occludin expression, suggesting impaired epithelial structural integrity. DICAM may act as an endogenous protective regulator against cisplatin-induced AKI by suppressing oxidative stress-mediated signaling and apoptosis. Further studies are needed to establish the underlying molecular mechanisms.