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

Abstract

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.

Improved Islet Morphology after Blockade of the Renin- Angiotensin System in the ZDF Rat

“…However, we saw no evidence of insulitis in this model. In addition, in the ZDF model, early extracellular matrix remodeling in the kidney seems to be independent of any inflammatory process (37). Finally, hypertension in the ZDF rat may also contribute to activation of the RAS and potentially to progressive ␤-cell dysfunction in this model (38).…”

Time-related changes in expression of collagen types I and III and of tenascin-C in rat bone mesenchymal stem cells under co-culture with ligament fibroblasts or uniaxial stretching

“…The cells became elongated and were rearranged after a 3-h uniaxial stretching. The relationship between the number of cells and the cell angular direction in control static experiments or during (Lavaud et al 2001) Forward: 5′-TGCCCACAGCCTTCTACACCT-3′ 244 58 5 10 Reverse: 5′-CAGCCATTCCTCCCACTCCAG-3′ Tenascin-C (Shen et al 2001) Forward: 5′-CAGAAGCTGAACCGGAAGTTG-3′ 278 55 10 11 Reverse: 5′-GGCTGTTGTTGCTATGGCQCT-3′ GAPDH (Beeres et al 2006) Forward: 5′-TCCCTCAAGATTGTCAGCAA-3′ 308 55 10 12 Reverse: 5′-AGATCCACAACGGATACATT-3′ stretching is displayed in Fig. 4.…”

High levels of myocardial antioxidant defense in aging nondiabetic normotensive Zucker obese rats

“…In conclusion, in the absence of hypertensive or hyperglycemic disorders, the heart seems to display a sufficient line of defense against oxidative stress during the development of cardiac hypertrophy. left ventricular hypertrophy; renal failure; oxidative stress; Zucker rats; hyperlipidemia ZUCKER OBESE RATS develop, at 3 mo and onward, severe structural alterations of the kidneys and renal impairment, leading to renal failure in 9-mo-old animals (31,36,37,44,48,61). We have recently shown that these alterations are initiated in the absence of hypertension, diabetes, and inflammatory cell infiltration (37) but might derive from an oxidative stress in kidney tissue (48,49).…”