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The klotho as a mediator of TGFβ1-dependent SMAD3 signaling in AV calcification. SMAD3 can mediate klotho-dependent TGFβ1 signaling. Lowering TGFβ1-dependent SMAD3 signaling also lowers SMAD1/5 signaling. Thus, klotho functions, in part, as a mediator by restraining or attenuating the augmented TGFβ/BMP signaling and TGFβ-regulated transcription of genes involved in CAVD.
