Epigenetic Regulation of VCAM-1 by Lipoxin A4 Is Renoprotective Against Diabetic Kidney Disease
Lipoxins (LXs) protect against diabetic kidney disease (DKD) by resolving chronic low-grade inflammation, but the exact mechanism by which this occurs is not known. We investigated the effect of LXs on inflammatory markers and the recruitment of macrophages to the diabetic glomerulus by using LXs as both a preventive and delayed interventional treatment in streptozotocin-induced diabetic ApoE knockout mice. Protection against DKD was associated with reduced glomerular macrophage accumulation. LXs also attenuated the expression of VCAM1 in glomerular endothelial cells. LXs protect against DKD in part by a mechanism that reduces VCAM1 gene expression via H3K4 monomethylation on the VCAM1 gene.
Authors
- Catherine Tighe
- Merlin C. Thomas (ORCID: https://orcid.org/0000-0003-0694-8743)
- Assam El‐Osta (ORCID: https://orcid.org/0000-0001-7968-7375)
- Patrick J. Guiry (ORCID: https://orcid.org/0000-0002-2612-8569)
- Ramtin Radman (ORCID: https://orcid.org/0000-0001-9835-0866)
- Muthukumar Mohan (ORCID: https://orcid.org/0000-0003-1044-146X)
- Phillip Kantharidis (ORCID: https://orcid.org/0000-0001-6260-1643)
- Kevin Gahan
- Jun Okabe (ORCID: https://orcid.org/0000-0002-7196-0522)
- Harikrishnan Kaipananickal (ORCID: https://orcid.org/0000-0002-4662-659X)
- Madhura Bose
- Victoria Priori
- Cooper Me
- Christos Tikellis
- K C Sourris
- K Jandeleit-Dahm
- Eoin Patrick Brennan
- Carolyn Chhor
- Catherine Godson
- Yvonne Zhang
Institutions
- University College Dublin (IE)
- Baker Heart and Diabetes Institute (AU)
- Inserm (FR)
- Université Paris Cité (FR)
- Centre de Recherche sur l'Inflammation (FR)
- Monash University (AU)
Publication Details
- Journal
- Diabetes
- Published
- 2026-02-18
- DOI
- https://doi.org/10.2337/db25-0970
- Primary Topic
- Chronic Kidney Disease and Diabetes
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Diabetes Australia Research Trust
- Juvenile Diabetes Research Foundation United States of America
- UCD Foundation
- Diabetes Australia
- Science Foundation Ireland
- Monash University
- Medical Research Council
- National Health and Medical Research Council