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

• Published in: British journal of nutrition 2021-04, Vol.125 (8), p.841-850
• Main Authors: Zhang, Zhi-Hui, Luo, Biao, Xu, Shen, Zhang, Zhi-Cheng, Xing, Wei-Yang, Chen, Yuan-Hua, Zhang, Cheng, Wang, Hua, Xie, Dong-Dong, Xu, De-Xiang
• Format: Article
• Language: English
• Subjects: Actin; Animal lactation; Animal sciences; Calciferol; Calcitriol; Collagen; Damage; Diet; E-cadherin; Extracellular matrix; Females; Fibrosis; Growth factors; Hyperplasia; Impairment; Inflammation; Juveniles; Kidney diseases; Kidneys; Laboratory animals; Mesenchyme; Middle age; mRNA; Muscles; N-Cadherin; Nutrient deficiency; Nutritional Endocrinology; Older people; Phosphatase; Phosphorylation; Pregnancy; Proteins; Renal function; Smad2 protein; Smooth muscle; Transforming growth factor-b1; Vimentin; Vitamin D; Vitamin D3; Vitamin deficiency; Weaning
• ISSN: 0007-1145; 1475-2662
• DOI: 10.1017/S0007114520003232

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-β mRNA were up-regulated. The in vitro experiment showed that 1,25-dihydroxyvitamin D3 alleviated transforming growth factor-β1 (TGF-β1)-mediated down-regulation of E-cadherin and inhibited TGF-β1-evoked up-regulation of N-cadherin, vimentin and α-SMA in renal epithelial HK-2 cells. Moreover, 1,25-dihydroxyvitamin D3 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.