Long-term vitamin D deficiency promotes renal fibrosis and functional impairment in middle-aged male mice.

Renal fibrosis is common especially in the elderly population. Recently, we found that vitamin D deficiency caused prostatic hyperplasia. This study aimed to investigate whether vitamin D deficiency promotes renal fibrosis and functional impairment. All mice except controls were fed with vitamin D deficient (VDD) diets, beginning from their early life. The absolute and relative kidney weights on postnatal week (PNW)20 were decreased in VDD diet-fed male pups but not in female pups. A mild pathological damage was observed in VDD diet-fed male pups but not in females. Further analysis showed that VDD-induced pathological damage was aggravated, accompanied by renal disfunction in 40-week-old male pups. An obvious collagen deposition was observed in VDD diet-fed 40-week-old male pups. Moreover, renal α-SMA, a marker of epithelial-mesenchymal transition (EMT), and Tgf-β mRNA were upregulated. The in vitro experiment showed that 1,25(OH)2D3 alleviated TGF-β1-mediated downregulation of E-cadherin and inhibited TGF-β1-evoked upregulation of N-cadherin, vimentin and α-SMA in renal epithelial HK-2 cells. Moreover, 1,25(OH)2D3 suppressed TGF-β1-evoked Smad2/3 phosphorylation in HK-2 cells. These results provide experimental evidence that long-term vitamin D deficiency promotes renal fibrosis and functional impairment, at least partially, through aggravating TGF-β/Smad2/3-mediated EMT in middle-aged male mice.