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Objective: Arterial stiffness is a component of arterial aging and might be related to decreased expression of Klotho. We performed Klotho RNA interference in human aortic vascular smooth muscle cells (HA-VSMC) to assess the effects of Klotho silencing on cell proliferation, cell migration, and the Wnt signaling pathway. Methods: Klotho expression in HA-VSMC was reduced by RNA interference. Cell proliferation and migration were determined by Cell Counting Kit-8 (CCK-8) assay and transwell assay, respectively. Results: Decreased expression of Klotho promotes the proliferation and migration of HA-VSMC. Furthermore, we found that decreased expression of Klotho led to the activation of the Wnt/β-catenin signaling pathway, with increased expression of multiple Wnt protein isoforms and β-catenin accompanied by increased expression of TCF4 and Cyclin D1, which are downstream target proteins of the Wnt/β-catenin signaling pathway. Additionally, the Wnt signaling pathway inhibitor XAV939 significantly inhibited the proliferation of HA-VSMC treated with shKlotho in a dose-dependent manner. Conclusion: Klotho deficiency promotes HA-VSMC proliferation and migration, and the Wnt/β-catenin signaling pathway may play an important role in the process of arterial stiffness related to vascular aging.

journal of bio innovation

KLOTHO DEFICIENCY PROMOTES THE PROLIFERATION AND MIGRATION OF HUMAN AORTIC VASCULAR SMOOTH MUSCLE CELLS BY ACTIVATING THE WNT/Β-CATENIN SIGNALING PATHWAY