Abstract
BackgroundCellular senescence may play a role in the development of kidney fibrosis, but its specific association with apoptosis or proliferation have yet to be determined.ObjectivesThis study aims to determine the effects of unilateral ureteral obstruction (UUO) on proliferation, cellular senescence and apoptosis in kidney fibrosis.MethodsA unilateral ureteral obstruction (UUO) procedure was performed to induce kidney fibrosis in 24 Swiss mice (3 months old, 30 g–40 g). Mice were sacrificed on day 3 (UUO3, n = 6), day 7 (UUO7, n = 6) and day 14 (UUO14, n = 6). Sham operation (SO) procedures were performed on the control group. The expression of Bcl-2, p16 and Bax mRNA was quantified with reverse transcription polymerase chain reaction (RT-PCR). Immunohistochemical (IHC) staining with anti-Bcl-2 and p53 antibodies was used to determine the localisation of proliferation and apoptosis. Data were analysed using one-way ANOVA followed by a post hoc least significant difference (LSD) test (P < 0.05)ResultsRT-PCR analysis showed higher mRNA expression of Bcl-2, p16 and Bax in the UUO groups compared with SO group (P < 0.05). Immunostaining showed that Bcl-2 and p53 expression in tubular epithelium in the UUO groups, except Bcl-2 expression was found in interstitial areas of UUO14 group.ConclusionSenescence in UUO might be associated with epithelial apoptosis and myofibroblast proliferation.
Highlights
Chronic kidney disease (CKD) is a worldwide public health issue that affects millions of people from all racial and ethnic backgrounds and its prevalence is increasing every year [1]
When compared with the Sham operation (SO) group, the ureteral obstruction (UUO) groups generally presented with tubular injuries that were characterised by a loss of brush border, tubular atrophy, tubular dilatation and the presence of intraluminal casts (Figure 1A)
The UUO3 group experienced tubular dilatation, shrinkage of the tubular basement membrane, widening of the interstitial space due to the accumulation of inflammatory cells, a loss of brush border and the presence of intraluminal casts (Figure 1B). The severity of these features increased in the UUO7 group (Figure 1C) and the UUO14 group presented with chaotic histological features that included atrophic tubules and very wide interstitial spaces that contained an accumulation of fibrotic and inflammatory cells (Figure 1D)
Summary
Chronic kidney disease (CKD) is a worldwide public health issue that affects millions of people from all racial and ethnic backgrounds and its prevalence is increasing every year [1]. Risk factors of CKD include hypertension, diabetes, obesity and primary kidney disorders [2]. These factors increase intraglomerular pressure, barrier filtration permeability, endothelial dysfunction, mesangial cell activation, podocyte and tubular cell counts and extracellular matrix synthesis, which collectively lead to kidney fibrosis [3]. Kidney fibrosis is closely related to tubular injury, which can induce proliferation, autophagy, cellular senescence, epithelial-mesenchymal transitions (EMT) and apoptosis [5]. Epithelial, fibroblast and myofibroblast cell proliferation are part of the cellular processes driving kidney fibrosis [5] as well as apoptosis, which occurs in damaged tubular cells [6]. Cellular senescence may play a role in the development of kidney fibrosis, but its specific association with apoptosis or proliferation have yet to be determined
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