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http://hdl.handle.net/2445/197290
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DC Field | Value | Language |
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dc.contributor.author | Roig-Soriano, Joan | - |
dc.contributor.author | Sánchez de Diego, Cristina | - |
dc.contributor.author | Esandi-Jauregui, Jon | - |
dc.contributor.author | Verdés, Sergi | - |
dc.contributor.author | Abraham, Carmela R. | - |
dc.contributor.author | Bosch, Assumpció | - |
dc.contributor.author | Ventura Pujol, Francesc | - |
dc.contributor.author | Chillón, Miguel | - |
dc.date.accessioned | 2023-04-26T17:55:43Z | - |
dc.date.available | 2023-04-26T17:55:43Z | - |
dc.date.issued | 2023-03-14 | - |
dc.identifier.issn | 2045-2322 | - |
dc.identifier.uri | http://hdl.handle.net/2445/197290 | - |
dc.description.abstract | The aging-protective gene α-Klotho (KL) produces two main transcripts. The full-length mRNA generates a transmembrane protein that after proteolytic ectodomain shedding can be detected in serum as processed Klotho (p-KL), and a shorter transcript which codes for a putatively secreted protein (s-KL). Both isoforms exhibit potent pleiotropic beneficial properties, although previous reports showed negative side effects on mineral homeostasis after increasing p-KL concentration exogenously. Here, we expressed independently both isoforms using gene transfer vectors, to assess s-KL effects on mineral metabolism. While mice treated with p-KL presented altered expression of several kidney ion channels, as well as altered levels of Pi and Ca2+ in blood, s-KL treated mice had levels comparable to Null-treated control mice. Besides, bone gene expression of Fgf23 showed a fourfold increase after p-KL treatment, effects not observed with the s-KL isoform. Similarly, bone microstructure parameters of p-KL-treated mice were significantly worse than in control animals, while this was not observed for s-KL, which showed an unexpected increase in trabecular thickness and cortical mineral density. As a conclusion, s-KL (but not p-KL) is a safe therapeutic strategy to exploit KL anti-aging protective effects, presenting no apparent negative effects over mineral metabolism and bone microstructure. | - |
dc.format.extent | 10 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Nature Publishing Group | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1038/s41598-023-31117-6 | - |
dc.relation.ispartof | Scientific Reports, 2023, vol. 13, num. 1 | - |
dc.relation.uri | https://doi.org/10.1038/s41598-023-31117-6 | - |
dc.rights | cc-by (c) Roig-Soriano, Joan et al., 2023 | - |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | - |
dc.source | Articles publicats en revistes (Ciències Fisiològiques) | - |
dc.subject.classification | Ossos | - |
dc.subject.classification | Ronyó | - |
dc.subject.classification | Animals | - |
dc.subject.classification | Ratolins (Animals de laboratori) | - |
dc.subject.other | Bones | - |
dc.subject.other | Kidney | - |
dc.subject.other | Animals | - |
dc.subject.other | Mice (Laboratory animals) | - |
dc.title | Differential toxicity profile of secreted and processed α-Klotho expression over mineral metabolism and bone microstructure | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 733482 | - |
dc.date.updated | 2023-04-26T17:55:43Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 36918615 | - |
Appears in Collections: | Articles publicats en revistes (Ciències Fisiològiques) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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733482.pdf | 3.32 MB | Adobe PDF | View/Open |
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