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

We examined the role of inflammation in the development of renal interstiti al fibrosis in Zucker obese rats, which rapidly present kidney lesions in t he absence of hypertension and hyperglycemia. Type I and III collagens were quantified using a polarized light and computer-assisted image analyzer. T he expression of mRNA encoding matrix components, adhesion molecules, chemo kines, and growth factors was followed by RT-PCR. The presence of synthesiz ed proteins as well as lymphocytes and macrophages was determined by immuno histochemistry. Interstitial fibrosis developed in two phases. The first ph ase 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 m o, interstitial fibrosis worsened with a large accumulation of type I colla gen, 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 pro cess afterward.