{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:36:58Z","timestamp":1788413818139,"version":"build-2803163510"},"reference-count":88,"publisher":"American Society for Clinical Investigation","issue":"23","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01-AR045955"],"award-info":[{"award-number":["R01-AR045955"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,12,5]]},"abstract":"<jats:p>\n                    Observations in transgenic \u03b1-\n                    <jats:italic>Klotho<\/jats:italic>\n                    (\n                    <jats:italic>Kl<\/jats:italic>\n                    ) mice (\n                    <jats:italic>Kl<\/jats:italic>\n                    <jats:sup>Tg<\/jats:sup>\n                    ) defined the antiaging role of soluble Klotho (sKL\n                    <jats:sup>130<\/jats:sup>\n                    ). A genetic translocation that elevates sKL levels in humans is paradoxically associated with increased circulating fibroblast growth factor 23 (FGF23) levels and the potential of both membrane KL (mKL\n                    <jats:sup>135<\/jats:sup>\n                    ) and sKL\n                    <jats:sup>130<\/jats:sup>\n                    to act as coreceptors for FGF23 activation of fibroblast growth factor receptors (FGFRs). Neither FGF23 expression nor the contributions of FGF23, mKL\n                    <jats:sup>135<\/jats:sup>\n                    , and sKL\n                    <jats:sup>130<\/jats:sup>\n                    codependent and independent functions have been investigated in\n                    <jats:italic>Kl<\/jats:italic>\n                    <jats:sup>Tg<\/jats:sup>\n                    mice. In the current study, we examined the effects of\n                    <jats:italic>Kl<\/jats:italic>\n                    overexpression on FGF23 levels and functions in\n                    <jats:italic>Kl<\/jats:italic>\n                    <jats:sup>Tg<\/jats:sup>\n                    mice. We found that mKL\n                    <jats:sup>135<\/jats:sup>\n                    but not sKL\n                    <jats:sup>130<\/jats:sup>\n                    stimulated FGF23 expression in osteoblasts, leading to elevated\n                    <jats:italic>Fgf23<\/jats:italic>\n                    bone expression and circulating levels in\n                    <jats:italic>Kl<\/jats:italic>\n                    <jats:sup>Tg<\/jats:sup>\n                    mice. Elevated FGF23 suppressed 1,25(OH)\n                    <jats:sub>2<\/jats:sub>\n                    D and parathyroid hormone levels but did not cause hypophosphatemic rickets in\n                    <jats:italic>Kl<\/jats:italic>\n                    <jats:sup>Tg<\/jats:sup>\n                    mice.\n                    <jats:italic>Kl<\/jats:italic>\n                    <jats:sup>Tg<\/jats:sup>\n                    mice developed low aldosterone\u2013associated hypertension but not left ventricular hypertrophy. Mechanistically, we found that mKL\n                    <jats:sup>135<\/jats:sup>\n                    and sKL\n                    <jats:sup>130<\/jats:sup>\n                    are essential cofactors for FGF23-mediated ERK activation but that they inhibited FGF23 stimulation of PLC-\u03b3 and PI3K\/AKT signaling. Thus, increased longevity in\n                    <jats:italic>Kl<\/jats:italic>\n                    <jats:sup>Tg<\/jats:sup>\n                    mice occurs in the presence of excess FGF23 that interacts with mKL and sKL to bias FGFR pathways.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.132820","type":"journal-article","created":{"date-parts":[[2019,12,4]],"date-time":"2019-12-04T11:01:08Z","timestamp":1575457268000},"source":"Crossref","is-referenced-by-count":40,"title":["FGF23 expression is stimulated in transgenic \u03b1-Klotho longevity mouse model"],"prefix":"10.1172","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3363-5673","authenticated-orcid":true,"given":"Zhousheng","family":"Xiao","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, 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