Mesangial Cell–Derived Exosomal miR‐4455 Induces Podocyte Injury in IgA Nephropathy by Targeting ULK2

Growing evidence suggests that mesangial cells (MCs) play a crucial role in the pathogenesis of IgA nephropathy (IgAN) by secreting aIgA1. However, the mechanism by which MCs regulate podocyte injury remains unknown. This study demonstrated that MC‐derived exosomes treated with aIgA1 induced podocyte injury in IgA nephropathy. miR‐4455, which was significantly upregulated in aIgA1 treatment MC‐derived exosomes, can be transferred from MCs to podocytes via exosomes. MC‐derived exosomal miR‐4455 induced podocyte injury. Mechanistically, exosomal miR‐4455 directly targeted ULK2 to regulate LC3II/I and P62 levels, which mediates autophagy homeostasis. This study revealed that MC‐derived exosomal miR‐4455 is a key factor affecting podocyte injury and provides a series of potential therapeutic targets for treating IgA nephropathy.