Specifically, the MDM2-downstream Notch1 pathway, responsible for cell differentiation during organism development, involves the Notch intracellular domain (NICD) in DN conditions, which can translocate into the nucleus and upregulate the expression of hairy and enhancer of split 1 (Hes1), leading to podocyte apoptosis in the glomerulus 27, 28. Here, HES1 is linked to liver dysplastic nodule.