Upregulation of p16, Bax and Bcl-2 mRNA Expression Associated with Epithelial Apoptosis and Myofibroblast Proliferation in Kidney Fibrosis Model in Mice

Background: 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.
Objectives: This study aims to determine the effects of unilateral ureteral obstruction (UUO) on proliferation, cellular senescence and apoptosis in kidney fibrosis.
Methods: A 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)
Results: RT-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.
Conclusion: Senescence in UUO might be associated with epithelial apoptosis and myofibroblast proliferation.

Keywords
UUO; kidney fibrosis; proliferation; cellular senescence; apoptosis; Bcl-2; p16; Bax