Dataset Information

Exercise-induced renal tubular Cdo1 protects against diabetic nephropathy

ABSTRACT: Exercise is an effective intervention for diabetic nephropathy (DN), but its molecular mechanisms remain incompletely understood. Here, we identify cysteine dioxygenase type 1 (Cdo1) as a mediator of exercise-induced renal protection. Exercise upregulates renal tubular Cdo1 expression via the α-ketoglutarate-TET-DNA demethylation pathway. Tubular epithelial cell-specific deletion of Cdo1 exacerbates DN and attenuates exercise-mediated alleviation of DN, whereas Cdo1 overexpression improves renal function and synergizes with exercise in ameliorating DN. Mechanistically, tubular Cdo1 promotes taurine production, which suppresses macrophage glycolysis and inflammatory activation by disrupting PKM2-HIF-1α interaction. Taurine supplementation rescues kidney injury in Cdo1-deficient mice, and alleviates DN in synergy with exercise. Thus, exercise ameliorates DN through Cdo1-mediated metabolic crosstalk between renal tubules and macrophages via the taurine-PKM2-HIF-1α axis.

ORGANISM(S): Mus musculus

PROVIDER: GSE334164 | GEO | 2026/06/09

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Renal hypoxia is widespread in acute kidney injury (AKI) of various aetiologies. Hypoxia adaptation, conferred through the hypoxia-inducible factor (HIF), appears to be insufficient. Here we show that HIF activation in renal tubules through Pax8-rtTA-based inducible knockout of von Hippel-Lindau protein (VHL-KO) protects from rhabdomyolysis-induced AKI. In this model, histological observations indicate that injury mainly affects proximal convoluted tubules, with 5% necrosis at d1 and 40% necrosis at d2. HIF-1alpha up-regulation in distal tubules reflects renal hypoxia. However, lack of HIF in proximal tubules suggests insufficient adaptation by HIF. AKI in VHL-KO mice leads to prominent HIF activation in all nephron segments, as well as to reduced serum creatinine, serum urea, tubular necrosis, and apoptosis marker caspase-3 protein. At d1 after rhabdomyolysis, when tubular injury is potentially reversible, HIF mediated protection in AKI is associated with activated glycolysis, cellular glucose uptake and utilization, autophagy, vasodilation, and proton removal as demonstrated by qPCR, pathway enrichment analysis and immunohistochemistry. Together, our data provide evidence for a HIF-orchestrated multi-level shift towards glycolysis as a major mechanism for protection against acute tubular injury. All experiments were carried out in transgenic mice in which selective renal tubular VHL knockout (VHL-KO) was inducible by doxycycline (Reference: Mathia S, Paliege A, Koesters R, Peters H, Neumayer HH, Bachmann S, Rosenberger C. Action of hypoxia-inducible factor in liver and kidney from mice with Pax8-rtTA-based deletion of von Hippel-Lindau protein. Acta Physiol (Oxf). 2013; 207(3):565-76.). Four groups of animals were used: 1) controls: untreated mice; 2) VHL-KO: injected with doxycycline (0.1 mg per 10 g body weight SC), 4 days prior to sacrifice; 3) AKI: rhabdomyolysis; 4) VHL-KO/AKI: doxycycline plus rhabdomyolysis. To induce AKI, 50% glycerol (0.05 ml per 10 g body weight) was injected IM into the left hind limb under isoflurane narcosis. Drinking water was withdrawn between 20 h prior and 24 h after glycerol injection.

Dataset Information

Exercise-induced renal tubular Cdo1 protects against diabetic nephropathy

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets