DI-UMONS : Dépôt institutionnel de l’université de Mons

Recherche transversale
(titres de publication, de périodique et noms de colloque inclus)
2009-10-28 - Colloque/Présentation - poster - Anglais - 1 page(s)

Sanchez A, You Y, Okada S., Decleves Anne-Emilie , Hall T, Sharma K, "Role of USF1 in mediating Angiotensin II Induced Kidney Disease." in Annual meeting of the American Society of Nephrology, San Diego, USA, 2009

  • Codes CREF : Biochimie (DI3112), Sciences biomédicales (DI3200), Néphrologie - urologie (DI3325), Diabétologie (DI3373), Physiologie pathologique (DI3250)
  • Unités de recherche UMONS : Biologie moléculaire (M122)
  • Instituts UMONS : Institut des Sciences et Technologies de la Santé (Santé)
  • Centres UMONS : Centre de Recherche UMONS-Ambroise Paré (UMHAP)

Abstract(s) :

(Anglais) Angiotensin II (angII) is known to function as a paracrine factor to stimulate a variety of genes involved in kidney disease progression, however the transcription factors involved are unclear. Upstream stimulatory 1 (USF1), a basic helix-loop helix leucine zipper transcription factor, has been shown to regulate renal TGF-β1 expression and is stimulated by high glucose. We hypothesized that angII stimulates USF1 thereby mediating gene expression in the in vivo model. USF1 knockout mice (KO) were backcrossed to the C57Bl6 strain (>7 generations). Adult male and female USF1 KO mice and C57Bl6 wild type (wt) controls were implanted with a subcutaneous mini-osmotic pump (Alzet 1004) to deliver either low dose angII (5 KO, 5 wt) or normal saline (NS) (4 KO, 5 wt) for 7 days. AngII was given at a subpressor dose of 200ng/kg/min. Body weights, kidney, and heart weights were assessed. Kidneys were isolated for analysis with quantitative real time PCR for USF1, USF2, TGF-β1, and type I collagen. Urine, plasma, and renal tissue was analyzed for TGF-β1 protein levels by ELISA with the Quantikine kit. P values were calculated using the student’s T test. In wild type mice, the delivery of low dose angII increased USF1 mRNA levels compared to wt controls receiving NS infusion (p=0.017). USF2 did not increase with angII infusion in either the wt or USF1 KO mice. USF1 KO mice receiving angII had significantly lower renal TGF-β1 levels than wt mice given angII (p=0.0195) or wt mice receiving NS (p=0.052). Type I collagen was decreased in USF1 KO mice receiving angII versus wt control (p=0.017). Kidney weight/body weight ratio was also significantly lower in this group than USF1 KO mice or wt mice receiving NS (p= 0.024, p= 0.013 respectively). In conclusion, delivery of low dose angII led to increased renal USF1 in wt mice. USF2 was not increased in USF1 KO mice receiving angII. USF1 KO mice had less renal hypertrophy, and lower TGF-β1 and type I collagen expression than wild type controls. This data indicates that in the in vivo model, USF1 is stimulated by angiotensin II and mediates several genes related to angII mediated kidney disease.