However, the sustained activation of Wnt/β-catenin signaling aggravated renal fibrosis.371 Loss of α-Klotho amplified Wnt/β-catenin signaling in patients and animals with CKD.372 ECM proteins such as fibronectin, partial EMT driver Snail-1, ECM degradation mediators MMP7 and PAI-1, and all the components of the RAAS are downstream targets of β-catenin.373,374 Wnt3a exacerbated IL-4- or TGF-β1-induced macrophage alternative M2 polarization. Here, SERPINE1 is linked to chronic kidney disease.