Changes of renal vitamin D metabolic enzyme expression and calcium transporter abundance in obstructive nephropathy

Abstract

The effects of urinary-tract obstruction on renal function have been clarified. However, there is little known about the change of renal vitamin D metabolic enzyme expression and vitamin D-dependent calcium transporting proteins expression in obstructive nephropathy. The male mice were subjected to unilateral ureteral obstruction (n = 10) or sham operation (n = 10). All mice were killed on day 7 after the surgical operation. Kidney sections were stained with Masson's trichrome and gene expression was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR. The obstructed kidney exhibited interstitial fibrosis as shown by the strong collagen deposition in the interstitium. Quantitative PCR results showed the increase of 1-OHase (P < 0.001) mRNA expression and the decrease of 24-OHase (P < 0.01), CaBP-9k (P < 0.01) and CaBP-28k (P < 0.01) mRNA expression in obstructed kidney as compared to that of the Sham group. In addition, the mRNA expression of 1-OHase and CaBP-9k was significantly increased and decreased, respectively, in obstructed kidney as compared to that of the contra-lateral kidney in unilateral ureteral obstruction (UUO) mice. Together, the present finding supports the hypothesis that the ureteral obstruction leads to the alteration of renal vitamin D metabolic enzyme expression and calcium transporter abundance, which may secondarily induce the abnormality of vitamin D endocrine system and bone health.

Early molecular responses of bone to obstructive nephropathy induced by unilateral ureteral obstruction in mice

“…The value of serum calcium in UUO mice was 2.02 mmol/L, which is below the lower limit of the normal range (2.07 mmol/L). Our recent kidney obstruction study using UUO mice demonstrated the altered renal vitamin D metabolism and a reduction of calcium transporter abundance 23 . Similar causes may account for the reduced level of serum calcium of UUO mice in this study.…”

Pathogenesis, Clinical Diagnosis and Treatment, and Animal Models for Ckd-Mbd

“…The mouse with unilateral ureteral obstruction (UUO) is a well-established model of tubulointerstitial fibrosis of the kidney as the interstitial fibrosis is a hallmark of chronic renal failure [60]. We previously reported the vitamin D signaling attenuates renal fibrosis in obstructive nephropathy by suppressing the renin-angiotensin system (RAS) [61], furthermore, we found the mice developed hypocalcaemia and hyperparathyroidism after 7 days of ureteric obstruction [62], and the down-regulation of Cbfa1 and Col mRNA expression ( Fig.…”

Trabecular bone deterioration at the greater trochanter of mice with unilateral obstructive nephropathy

“…3 We previously reported changes in the renal expression of vitamin D metabolic enzymes and changes in calcium transporter abundance following obstructive nephropathy in mice subjected to UUO 4 and demonstrated early molecular responses of bone to unilateral obstructive nephropathy in the UUO model. 5 However, associated with the pathological alterations of vitamin D metabolism and the expression of genes involved in bone metabolism, whether trabecular bone microstructure would deteriorate in UUO mice remained to be clarified.…”