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

• Published in: Biomedicine & pharmacotherapy 2024-08, Vol.177, p.116923, Article 116923
• Main Authors: Perez-Moreno, Elisa, Toledo, Tomás, Campusano, Pascale, Zuñiga, Sebastián, Azócar, Lorena, Feuerhake, Teo, Méndez, Gonzalo P., Labarca, Mariana, Pérez-Molina, Francisca, de la Peña, Adely, Herrera-Cid, Cristian, Ehrenfeld, Pamela, Godoy, Alejandro S., González, Alfonso, Soza, Andrea
• Format: Article
• Language: English
• Subjects: Acute kidney injury; Acute Kidney Injury - chemically induced; Acute Kidney Injury - drug therapy; Acute Kidney Injury - metabolism; Acute Kidney Injury - pathology; Acute Kidney Injury - prevention & control; AKI-to-CKD transition; Animals; Disease Models, Animal; Disease Progression; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Epithelial Cells - pathology; Epithelial-mesenchymal plasticity; Epithelial-mesenchymal transition; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibroblasts - pathology; Fibrosis; Folic acid; Folic Acid - pharmacology; Galectin-8; Galectins - metabolism; Kidney - drug effects; Kidney - metabolism; Kidney - pathology; Male; Mice; Mice, Inbred C57BL
• ISSN: 0753-3322; 1950-6007; 1950-6007
• DOI: 10.1016/j.biopha.2024.116923

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. [Display omitted] •Gal-8 preserves kidney function in folic acid-induced AKI.•Gal-8 reduces acute renal cortical damage in folic acid-induced AKI.•Gal-8 has an anti-fibrotic effect in folic acid-induced kidney injury.•Gal-8 decreases fibroblast activation in folic acid-induced kidney injury.