Deficiency of Nuclear Receptor Coactivator 3 Aggravates Diabetic Kidney Disease by Impairing Podocyte Autophagy.
Adv Sci (Weinh)
; 11(19): e2308378, 2024 May.
Article
de En
| MEDLINE
| ID: mdl-38483947
ABSTRACT
Nuclear receptors (NRs) are important transcriptional factors that mediate autophagy, preventing podocyte injury and the progression of diabetic kidney disease (DKD). However, the role of nuclear receptor coactivators that are powerful enhancers for the transcriptional activity of NRs in DKD remains unclear. In this study, a significant decrease in Nuclear Receptor Coactivator 3 (NCOA3) is observed in injured podocytes caused by high glucose treatment. Additionally, NCOA3 overexpression counteracts podocyte damage by improving autophagy. Further, Src family member, Fyn is identified to be the target of NCOA3 that mediates the podocyte autophagy process. Mechanistically, NCOA3 regulates the transcription of Fyn in a nuclear receptor, PPAR-γ dependent way. Podocyte-specific NCOA3 knockout aggravates albuminuria, glomerular sclerosis, podocyte injury, and autophagy in DKD mice. However, the Fyn inhibitor, AZD0530, rescues podocyte injury of NCOA3 knockout DKD mice. Renal NCOA3 overexpression with lentivirus can ameliorate podocyte damage and improve podocyte autophagy in DKD mice. Taken together, the findings highlight a novel target, NCOA3, that protects podocytes from high glucose injury by maintaining autophagy.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Autophagie
/
Souris knockout
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Néphropathies diabétiques
/
Podocytes
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Coactivateur-3 de récepteur nucléaire
Limites:
Animals
/
Humans
/
Male
Langue:
En
Journal:
Adv Sci (Weinh)
/
Advanced science (Weinheim)
Année:
2024
Type de document:
Article
Pays d'affiliation:
Chine
Pays de publication:
Allemagne