p16 Ink4a , a marker of cellular senescence, is associated with renal disease in the B6. NZMSle1/Sle2/Sle3 mouse model of lupus.

Autor:	Tilman G; de Duve Institute, Université catholique de Louvain, Brussels, Belgium.; Department of Rheumatology, Cliniques universitaires Saint-Luc, Brussels, Belgium., Dupré E; de Duve Institute, Université catholique de Louvain, Brussels, Belgium., Watteyne L; de Duve Institute, Université catholique de Louvain, Brussels, Belgium., Baert CA; de Duve Institute, Université catholique de Louvain, Brussels, Belgium., Nolf D; de Duve Institute, Université catholique de Louvain, Brussels, Belgium., Benhaddi F; de Duve Institute, Université catholique de Louvain, Brussels, Belgium., Lambert F; de Duve Institute, Université catholique de Louvain, Brussels, Belgium., Daumerie A; IREC Imaging Platform (2IP), Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium., Bouzin C; IREC Imaging Platform (2IP), Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium., Lucas S; de Duve Institute, Université catholique de Louvain, Brussels, Belgium., Limaye N; de Duve Institute, Université catholique de Louvain, Brussels, Belgium nisha.limaye@uclouvain.be.
Jazyk:	angličtina
Zdroj:	Lupus science & medicine [Lupus Sci Med] 2023 Oct; Vol. 10 (2).
DOI:	10.1136/lupus-2023-001010
Abstrakt:	Objectives: Despite treatment, one-third of patients with lupus nephritis (LN) show a decline in renal function. Prognostic markers of poor outcome as well as novel therapeutic targets are therefore highly sought. We showed that p16 INK4a , a marker of cellular senescence, is observed in baseline kidney biopsies from patients with LN, and is associated with renal disease. Here, we set out to assess for whether these findings are recapitulated in the B6. NZMSle1/Sle2/Sle3 (B6. Sle1.2.3 ) mouse model of spontaneous lupus. Methods: We evaluated the occurrence and time of onset of p16 Ink4a staining by immunohistochemistry on kidney sections, and tested for its association with multiple renal and systemic disease parameters, fibrosis and CD8 + T cell infiltration, in two cohorts of B6. Sle1.2.3 mice. Results: The presence of p16 Ink4a -positive cells in kidney was significantly associated with increased urine albumin/creatinine ratio, histopathological scores, CD8 + T cell infiltration and fibrosis, in both B6. Sle1.2.3 cohorts. In contrast, p16 Ink4a staining was not associated with systemic disease parameters. A time course showed that systemic disease parameters as well as glomerular IgG deposits appeared in B6. Sle1.2.3 mice by 4 months of age; the appearance of p16 Ink4a -positive cells occurred later, by 8 months of age, overlapping with renal disease. Conclusion: We report, for the first time, the presence of p16 Ink4a -positive cells, a marker of cellular senescence, in the B6. Sle1.2.3 kidney, and their association with renal disease severity. This provides a preclinical model in which to test for the role of cellular senescence in the pathogenesis of LN, as a potential kidney-intrinsic disease mechanism. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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