The anti-aging protein Klotho affects early postnatal myogenesis by downregulating Jmjd3 and the canonical Wnt pathway.

Autor: McKee CM; Molecular, Cellular & Integrative Physiology Program, University of California, Los Angeles, California, USA., Chapski DJ; Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA., Wehling-Henricks M; Department of Integrative Biology and Physiology, University of California, Los Angeles, California, USA., Rosa-Garrido M; Department of Biomedical Engineering, School of Medicine and School of Engineering, University of Alabama at Birmingham, Birmingham, USA., Kuro-O M; Division of Anti-Aging Medicine, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Japan., Vondriska TM; Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.; Departments of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.; Departments of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA., Tidball JG; Molecular, Cellular & Integrative Physiology Program, University of California, Los Angeles, California, USA.; Department of Integrative Biology and Physiology, University of California, Los Angeles, California, USA.; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA.
Jazyk: angličtina
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2022 Mar; Vol. 36 (3), pp. e22192.
DOI: 10.1096/fj.202101298R
Abstrakt: Modulating the number of muscle stems cells, called satellite cells, during early postnatal development produces long-term effects on muscle growth. We tested the hypothesis that high expression levels of the anti-aging protein Klotho in early postnatal myogenesis increase satellite cell numbers by influencing the epigenetic regulation of genes that regulate myogenesis. Our findings show that elevated klotho expression caused a transient increase in satellite cell numbers and slowed muscle fiber growth, followed by a period of accelerated muscle growth that leads to larger fibers. Klotho also transcriptionally downregulated the H3K27 demethylase Jmjd3, leading to increased H3K27 methylation and decreased expression of genes in the canonical Wnt pathway, which was associated with a delay in muscle differentiation. In addition, Klotho stimulation and Jmjd3 downregulation produced similar but not additive reductions in the expression of Wnt4, Wnt9a, and Wnt10a in myogenic cells, indicating that inhibition occurred through a common pathway. Together, our results identify a novel pathway through which Klotho influences myogenesis by reducing the expression of Jmjd3, leading to reductions in the expression of Wnt genes and inhibition of canonical Wnt signaling.
(© 2022 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)
Databáze: MEDLINE
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