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Elevated serum 1,25(OH)2-vitamin D3 level attenuates renal tubulointerstitial
fibrosis induced by unilateral ureteral obstruction in kl/kl mice
#MMPMID25297969
Sun Y
; Zhou G
; Gui T
; Shimokado A
; Nakanishi M
; Oikawa K
; Sato F
; Muragaki Y
Sci Rep
2014[Oct]; 4
(?): 6563
PMID25297969
show ga
Previous studies have suggested that Klotho provides reno-protection against
unilateral ureteral obstruction (UUO)-induced renal tubulointerstitial fibrosis
(RTF). Because the existing studies are mainly performed using heterozygous
Klotho mutant (HT) mice, we focused on the effect of UUO on homozygous Klotho
mutant (kl/kl) mice. UUO kidneys from HT mice showed a significantly higher level
of RTF and TGF-?/Smad3 signaling than wild-type (WT) mice, whereas both were
greatly suppressed in kl/kl mice. Primary proximal tubular epithelial culture
cells isolated from kl/kl mice showed no suppression in TGF-?1-induced epithelial
mesenchymal transition (EMT) compared to those from HT mice. In the renal
epithelial cell line NRK52E, a large amount of inorganic phosphate (Pi), FGF23,
or calcitriol was added to the medium to mimic the in vivo homeostasis of kl/kl
mice. Neither Pi nor FGF23 antagonized TGF-?1-induced EMT. In contrast,
calcitriol ameliorated TGF-?1-induced EMT in a dose dependent manner. A vitamin
D3-deficient diet normalized the serum 1,25 (OH)2 vitamin D3 level in kl/kl mice
and enhanced UUO-induced RTF and TGF-?/Smad3 signaling. In conclusion, the
alleviation of UUO-induced RTF in kl/kl mice was due to the TGF-?1 signaling
suppression caused by an elevated serum 1, 25(OH)2 vitamin D3.
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