Endoplasmic reticulum (ER) stress is involved in the process of kidney
fibrosis. Spliced
X-box binding protein 1 (XBP1S) is the key mediator of ER stress while its role in
fibrosis is still poorly understood. This study was aimed to investigate the role of XBP1S in renal
fibrosis and evaluate whether
valsartan could alleviate
fibrosis through XBP1S. Renal interstitial
fibrosis was induced by unilateral
ureteral obstruction (UUO) in C57BL/6 mice, and UUO mice were daily administered with
valsartan (20 mg/kg) through oral gavage. After 7 days of UUO, at
euthanasia, left kidney was collected to examine the histological alteration by using haematoxylin-
eosin staining, Masson's trichrome staining, Sirius red staining and immunohistochemistry. Western blot was used to assess XBP1S, targets of XBP1S,
fibronectin, α-SMA, BAX and BCL2
protein levels. Real-time polymerase chain reaction was performed to assess
NADPH oxidase subunits p47-phox and
p67-phox mRNA levels. The results showed that XBP1S expression was decreased by about 70% in the UUO mice compared with that in
sham mice (P < 0.01), which was reversed by
valsartan administration (P < 0.05). Meanwhile, UUO-induced renal interstitial
fibrosis was attenuated by
valsartan treatment. In addition, the
protein levels of
fibronectin and α-SMA were upregulated by UUO induction (P < 0.01), and
valsartan administration inhibited the
protein levels of
fibronectin and α-SMA in UUO mice (P < 0.05). Western blot analysis showed that the ratio of BAX to BCL2
protein level was increased in UUO model compared with that in
sham mice, and the increment also was diminished by
valsartan treatment (P < 0.05). Finally, UUO-induced
mRNA levels of p47-phox and
p67-phox were significantly attenuated by
valsartan administration (P < 0.05). These results showed that
valsartan at least partly restores renal interstitial
fibrosis by enhancing XBP1S activation through inhibiting oxidative stress and apoptosis in the UUO mice. These results suggest that XBP1S could be a potential therapeutic target for kidney
fibrosis.