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Endocrine
Erschienen in: Endocrine 2/2016

09.07.2016 | Original Article

In vitro and in vivo inhibition of mTOR by 1,25-dihydroxyvitamin D3 to improve early diabetic nephropathy via the DDIT4/TSC2/mTOR pathway

verfasst von: Hang Wang, Jianmin Wang, Hua Qu, Huili Wei, Baolan ji, Zesong Yang, Jing Wu, Qin He, Yuanyuan Luo, Dan Liu, Yang Duan, Fang Liu, Huacong Deng

Erschienen in: Endocrine | Ausgabe 2/2016

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Abstract

We investigated whether 1,25-dihydroxy-vitamin D3 (1,25(OH)2D3) could improve early diabetic nephropathy through the DNA-damage-inducible transcript 4/tuberous sclerosis 2/mammalian target of rapamycin pathway. Rat mesangial cells were cultured in media containing normal glucose or high glucose and were treated with or without 1,25(OH)2D3. Mesangial cells proliferation was measured. Streptozotocin-induced diabetic rats were injected intravenously with a recombinant lentivirus against the rat vitamin D receptor gene. Urinary and serum albumin, fasting plasma glucose, serum triglyceride, total cholesterol, calcium, parathyroid hormone and serum 25-dihydroxy-vitamin D (25(OH)D) levels, mean glomerular volume, glomerular basement membrane thickness and total kidney volume were determined. The expressions of vitamin D receptor, DNA-damage-inducible transcript 4, and mammalian target of rapamycin were measured. 1,25(OH)2D3 inhibited the proliferation of mesangial cells induced by hyperglycemia. 1,25(OH)2D3 also significantly reduced albumin excretion, mean glomerular volume, glomerular basement membrane, and total kidney volume in rats with diabetic nephropathy. The expression of DNA-damage-inducible transcript 4 was elevated by 1,25(OH)2D3 treatment. The phosphorylation of mammalian target of rapamycin was reduced by 1,25(OH)2D3 treatment. Vitamin D receptor gene silencing blocked all of the above results. The current study demonstrates that 1,25(OH)2D3 can effectively inhibit mesangial cells proliferation induced by hyperglycemia, thus suppressing the development of diabetic nephropathy. This study also shows that the nephron-protective effect of 1,25(OH)2D3 occurs partly through the DDIT4/TSC2/mTOR pathway.
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Metadaten
Titel
In vitro and in vivo inhibition of mTOR by 1,25-dihydroxyvitamin D3 to improve early diabetic nephropathy via the DDIT4/TSC2/mTOR pathway
verfasst von
Hang Wang
Jianmin Wang
Hua Qu
Huili Wei
Baolan ji
Zesong Yang
Jing Wu
Qin He
Yuanyuan Luo
Dan Liu
Yang Duan
Fang Liu
Huacong Deng
Publikationsdatum
09.07.2016
Verlag
Springer US
Erschienen in
Endocrine / Ausgabe 2/2016
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-016-0999-1

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