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Potential mechanisms for Smad3 to promote cisplatin-induced acute kidney injury. Cisplatin activates Smad3 phosphorylation and then decreases lncRNA Arid2-IR, thus causing tubular epithelial cell (TEC) growth arrest at the G1 cell cycle. Inhibiting Smad3 (SIS3) reduced Smad3 phosphorylation and then increased lncRNA Arid2-IR by binding to TFRC, improving cell cycle disorders, decreasing cell apoptosis, and increasing cell regeneration.
