Targeted deletion of kidney glucose-6 phosphatase leads to nephropathy
| Autor: | Gilles Mithieux, Julie Clar, Yann Herault, Marie-Christine Birling, Fabienne Rajas, Julien Calderaro, G. Peter A. Smit, Blandine Gri |
|---|---|
| Přispěvatelé: | Université de Lyon, Nutrition et cerveau (U1213, U855), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Le génie génétique et la conception [Illkirch-Graffenstaden], Institut Clinique de la Souris (ICS), Department of Pediatrics [Groningen], Universitair Medisch Centrum Groningen, Di Carlo, Marie-Ange |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
G6PC TERM CLINICAL-COURSE TO-MESENCHYMAL TRANSITION Glycogen Storage Disease Type I Podocyte Renin-Angiotensin System Diabetic nephropathy Mice chemistry.chemical_compound Glomerular Filtration Barrier TGF-β1 Glycogen storage disease Mice Knockout Kidney SMALL-INTESTINE Glycogen Podocytes LIVER-TRANSPLANTATION 3. Good health CRE RECOMBINASE CONTINUOUS GLUCOSE THERAPY Kidney Tubules medicine.anatomical_structure Nephrology Glucose-6-Phosphatase nephropathy PHOSPHATIDYLINOSITOL 3-KINASE Kidney Diseases [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] medicine.symptom Dilatation Pathologic Signal Transduction medicine.medical_specialty microalbuminuria epithelial-mesenchymal transition Biology Article Nephropathy DIABETIC-NEPHROPATHY Transforming Growth Factor beta1 glycogen storage disease Internal medicine medicine Albuminuria Animals microalbumineria [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] podocyte injury RENAL LIPID-METABOLISM GLYCOGEN-STORAGE-DISEASE Lipid Metabolism medicine.disease Disease Models Animal Endocrinology gluconeogenesis chemistry Nephromegaly |
| Zdroj: | Kidney International Kidney International, Nature Publishing Group, 2014, 86 (4), pp.747-756. ⟨10.1038/ki.2014.102⟩ Kidney International, 86(4), 747-756. ELSEVIER SCIENCE INC |
| ISSN: | 0085-2538 1523-1755 |
| DOI: | 10.1038/ki.2014.102 |
| Popis: | International audience; Renal failure is a major complication that arises with aging in glycogen storage disease type1a and type 1b patients. In the kidneys, glucose-6 phosphatase catalytic subunit (encoded byG6pc) deficiency leads to the accumulation of glycogen; this effect results in markednephromegaly and progressive glomerular hyperperfusion and hyperfiltration, whichprecede the development of microalbuminuria and proteinuria. To better understand theend-stage nephropathy in glycogen storage disease type 1a, we generated a novel kidneyspecificG6pc knock-out (K-G6pc-/-) mouse, which exhibited normal life expectancy. After 6months of G6pc deficiency, K-G6pc-/- mice showed glycogen overload leading tonephromegaly and tubular dilation. Moreover, renal accumulation of lipids due to activationof de novo lipogenesis was observed. This led to the activation of the renin-angiotensinsystem and the development of epithelial-mesenchymal transition process and podocyteinjury via transforming growth factor β1 signaling. Thus, K-G6pc-/- mice developedmicroalbuminuria caused by the impairment of glomerular filtration barrier. In conclusion,renal G6pc deficiency alone is sufficient to induce the development of the early onsetnephropathy observed in glycogen storage disease type 1a, independently of the liverdisease. K-G6pc-/- mouse model is a unique tool to decipher the molecular mechanismsunderlying renal failure and to evaluate potential therapeutic strategies. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|