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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/197290
Differential toxicity profile of secreted and processed α-Klotho expression over mineral metabolism and bone microstructure
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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.
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ROIG-SORIANO, Joan, SÁNCHEZ DE DIEGO, Cristina, ESANDI-JAUREGUI, Jon, VERDÉS, Sergi, ABRAHAM, Carmela, BOSCH, Assumpció, VENTURA PUJOL, Francesc, CHILLÓN, Miguel. Differential toxicity profile of secreted and processed α-Klotho expression over mineral metabolism and bone microstructure. _Scientific Reports_. 2023. Vol. 13, núm. 1. [consulta: 26 de febrer de 2026]. ISSN: 2045-2322. [Disponible a: https://hdl.handle.net/2445/197290]