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2023-03-14

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cc-by (c) Roig-Soriano, Joan et al., 2023
Please use this identifier to cite or link to this item: 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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https://doi.org/10.1038/s41598-023-31117-6

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.

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Ossos, Ronyó, Animals, Ratolins (Animals de laboratori)

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Bones, Kidney, Animals, Mice (Laboratory animals)

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Articles publicats en revistes (Ciències Fisiològiques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citation

ROIG-SORIANO, Joan, et al. Differential toxicity profile of secreted and processed α-Klotho expression over mineral metabolism and bone microstructure. Scientific Reports. 2023. Vol. 13, num. 1. ISSN 2045-2322. [consulted: 12 of August of 2026]. Available at: https://hdl.handle.net/2445/197290

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