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Am J Physiol Renal Physiol 280: F683-F694, 2001;
0363-6127/01 $5.00
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Vol. 280, Issue 4, F683-F694, April 2001

Inflammation is probably not a prerequisite for renal interstitial fibrosis in normoglycemic obese rats

Stéphanie Lavaud1, Bruno Poirier1, Chantal Mandet1, Marie-France Bélair1, Théano Irinopoulou1, Didier Heudes1, Raymond Bazin2, Jean Bariéty1, Isaac Myara1,3, and Jacques Chevalier1

1 Institut National de la Santé et de la Recherche Médicale Unité 430, Broussais Hospital, 75014 Paris; Claude Bernard Association, 2 Institut National de la Santé et de la Recherche Médicale Unité 465, Institut des Cordeliers, 75005 Paris; and 3 Laboratory of Applied Biochemistry, Faculty of Pharmaceutical and Biological Sciences, 92296 Châtenay-Malabry, France

We examined the role of inflammation in the development of renal interstitial fibrosis in Zucker obese rats, which rapidly present kidney lesions in the absence of hypertension and hyperglycemia. Type I and III collagens were quantified using a polarized light and computer-assisted image analyzer. The expression of mRNA encoding matrix components, adhesion molecules, chemokines, and growth factors was followed by RT-PCR. The presence of synthesized proteins as well as lymphocytes and macrophages was determined by immunohistochemistry. Interstitial fibrosis developed in two phases. The first phase occurred as early as 3 mo and resulted from a neosynthesis of type III collagen and fibronectin and a reduction of extracellular matrix catabolism, in parallel with an overexpression of transforming growth factor-beta 1 and in the absence of any lymphocyte or macrophage infiltration. After 6 mo, interstitial fibrosis worsened with a large accumulation of type I collagen, concomitantly with a large macrophage infiltration. Thus inflammation cannot explain the onset of interstitial fibrosis that developed in young, insulinoresistant, normoglycemic, obese Zucker rats but aggravated this process afterward.

Zucker rat; hyperlipidemia; hyperinsulinemia; collagen; fibronectin; tissue inhibitor of metalloproteinase-1; transforming growth factor-beta 1


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