Galectin-8 counteracts folic acid-induced acute kidney injury and prevents its transition to fibrosis

Autor: Elisa Perez-Moreno, Tomás Toledo, Pascale Campusano, Sebastián Zuñiga, Lorena Azócar, Teo Feuerhake, Gonzalo P. Méndez, Mariana Labarca, Francisca Pérez-Molina, Adely de la Peña, Cristian Herrera-Cid, Pamela Ehrenfeld, Alejandro S. Godoy, Alfonso González, Andrea Soza
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Biomedicine & Pharmacotherapy, Vol 177, Iss , Pp 116923- (2024)
Druh dokumentu: article
ISSN: 0753-3322
DOI: 10.1016/j.biopha.2024.116923
Popis: Acute kidney injury (AKI), characterized by a sudden decline in kidney function involving tubular damage and epithelial cell death, can lead to progressive tissue fibrosis and chronic kidney disease due to interstitial fibroblast activation and tissue repair failures that lack direct treatments. After an AKI episode, surviving renal tubular cells undergo cycles of dedifferentiation, proliferation and redifferentiation while fibroblast activity increases and then declines to avoid an exaggerated extracellular matrix deposition. Appropriate tissue recovery versus pathogenic fibrotic progression depends on fine-tuning all these processes. Identifying endogenous factors able to affect any of them may offer new therapeutic opportunities to improve AKI outcomes. Galectin-8 (Gal-8) is an endogenous carbohydrate-binding protein that is secreted through an unconventional mechanism, binds to glycosylated proteins at the cell surface and modifies various cellular activities, including cell proliferation and survival against stress conditions. Here, using a mouse model of AKI induced by folic acid, we show that pre-treatment with Gal-8 protects against cell death, promotes epithelial cell redifferentiation and improves renal function. In addition, Gal-8 decreases fibroblast activation, resulting in less expression of fibrotic genes. Gal-8 added after AKI induction is also effective in maintaining renal function against damage, improving epithelial cell survival. The ability to protect kidneys from injury during both pre- and post-treatments, coupled with its anti-fibrotic effect, highlights Gal-8 as an endogenous factor to be considered in therapeutic strategies aimed at improving renal function and mitigating chronic pathogenic progression.
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