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TNF-α induces expression of RARRES1, which is cleaved into soluble RARRES1, potentially mediated by inflammation-stimulated MMP. The soluble RARRES1 is then endocytosed and interacts with intracellular RIOK1. The interaction between RIOK1 and RARRES1 leads to the inactivation of RIOK1, thereby activating p53 and the subsequent apoptosis pathway. Podocyte loss is a key event for progression of DKD and FSGS.
