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- Title
Active vitamin D and its analogue, 22-oxacalcitriol, ameliorate puromycin aminonucleoside-induced nephrosis in rats.
- Authors
Matsui, Isao; Hamano, Takayuki; Tomida, Kodo; Inoue, Kazunori; Takabatake, Yoshitsugu; Nagasawa, Yasuyuki; Kawada, Noritaka; Ito, Takahito; Kawachi, Hiroshi; Rakugi, Hiromi; Imai, Enyu; Isaka, Yoshitaka
- Abstract
Background. Recent studies have demonstrated that podocyte injury, which results in proteinuria, leads to tubulointerstitial fibrosis. Although some studies have revealed that vitamin D administration protects renal structure and function in mesangial cell proliferative and/or excessive matrix productive models, the effects of vitamin D on podocyte injury have remained uncertain. Methods. In this study, we examined whether administration of active vitamin D (calcitriol) or its analogue, 22-oxacalcitriol (maxacalcitol), is preventative in podocyte injury using the puromycin aminonucleoside nephrosis model with neither mesangial proliferation nor matrix accumulation. Results. Before the onset of proteinuria, renal 1α-hydroxylase and 24-hydroxylase were markedly down-regulated and up-regulated, respectively, leading to impaired vitamin D activation. Thereafter, serum 25-hydroxyvitamin D decreased along with the increased excretion of vitamin D-binding protein in urine. After confirming that podocytes express vitamin D receptor and all retinoid X receptors (RXRs) except RXR-α, we found that daily administration of calcitriol or its analogue 22-oxacalcitriol ameliorated the nephrotic state by protecting podocytes, as shown by the reduced staining of desmin (podocyte injury marker) and the upregulation of nephrin and podocin. These data suggest that the impairment of the vitamin D system plays a role in increasing proteinuria in podocyte injury. Conclusions. We demonstrated the breakdown of the vitamin D activation system in podocyte injury, and established a preventative role for vitamin D in podocyte injury.
- Subjects
THERAPEUTIC use of vitamin D; PUROMYCIN; DRUG side effects; KIDNEY injuries; LABORATORY rats; VITAMIN D; EPITHELIAL cells; PROTEINURIA; FIBROSIS
- Publication
Nephrology Dialysis Transplantation, 2009, Vol 24, Issue 8, p2354
- ISSN
0931-0509
- Publication type
Article
- DOI
10.1093/ndt/gfp117