Long-term vitamin D deficiency promotes renal fibrosis and functional impairment in middle-aged male mice.
Br J Nutr
; 125(8): 841-850, 2021 04 28.
Article
en En
| MEDLINE
| ID: mdl-32812524
ABSTRACT
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 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 dysfunction in 40-week-old male pups. An obvious collagen deposition was observed in VDD diet-fed 40-week-old male pups. Moreover, renal α-smooth muscle actin (α-SMA), a marker of epithelial-mesenchymal transition (EMT), and Tgf-ß mRNA were up-regulated. The in vitro experiment showed that 1,25-dihydroxyvitamin D3 alleviated transforming growth factor-ß1 (TGF-ß1)-mediated down-regulation of E-cadherin and inhibited TGF-ß1-evoked up-regulation of N-cadherin, vimentin and α-SMA in renal epithelial HK-2 cells. Moreover, 1,25-dihydroxyvitamin D3 suppressed TGF-ß1-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-ß/Smad2/3-mediated EMT in middle-aged male mice.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Deficiencia de Vitamina D
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Riñón
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Enfermedades Renales
Tipo de estudio:
Etiology_studies
Límite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Br J Nutr
Año:
2021
Tipo del documento:
Article