Maternal obesity induces macrophage to myofibroblast transition in kidneys of male offspring through a pathway driven by 20-hydroxyeicosatetraenoic acid - PubMed
3 days ago
- #Chronic Kidney Disease
- #Macrophage Transition
- #Maternal Obesity
- Maternal obesity increases the risk of chronic kidney disease (CKD) in male offspring, affecting over 800 million people globally.
- The study finds that maternal obesity leads to macrophage to myofibroblast transition (MMT) in offspring kidneys via a pathway involving 20-hydroxyeicosatetraenoic acid (20-HETE).
- 20-HETE from proximal tubules promotes mitochondrial hyperactivity and MMT through the Ffar1 receptor in macrophages, worsening kidney pathology.
- Targeting 20-HETE or depleting Ffar1 in offspring reduces kidney disease, suggesting potential therapeutic strategies.
- Hormone screening identifies T3 (3,3,5-Triiodo-L-thyronine) as enhancing Ffar1 expression via the TRβ-P300-BRD4 regulatory axis, highlighting T3 and 20-HETE co-activation in MMT.
- The research is supported by grants from the National Natural Science Foundation of China and the Shanghai Municipal Science and Technology Commission, with related patent applications pending.