1,25-Dihydroxyvitamin D3 inhibits the proliferation of rat mesangial cells induced by high glucose via DDIT4
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Da-Peng Chen1,2,*, Ye-Ping Ma1,2,*, Li Zhuo2, Zheng Zhang1,2, Gu-Ming Zou2, Yue Yang2, Hong-Mei Gao2 and Wen-Ge Li1,2
1Graduate School of Peking Union Medical College, Beijing 100730, China
2Department of Nephrology, China-Japan Friendship Hospital, Beijing 100029, China
*These authors share co-first authorship
Wen-Ge Li, email: [email protected]
Keywords: diabetic nephropathy; 1,25-Dihydroxyvitamin D3; proliferation; DDIT4; mTOR
Received: July 31, 2017 Accepted: November 14, 2017 Published: December 09, 2017
1,25-Dihydroxyvitamin D3(1,25(OH)2 D3) is a secosteroid with antiproliferative property. It also plays a pivotal renoprotective role in diabetic nephropathy. We investigated whether 1,25(OH)2D3 could inhibit the proliferation of rat mesangial cells exposed to high glucose via the DNA-damage-inducible transcript 4/mammalian target of rapamycin(DDIT4/mTOR) pathway. The cell proliferation rate and cell cycle duration were measured using cell counting kit-8 assay and flow cytometry. Protein expression was assayed by Western blot. Glucose acted as a growth factor in rat mesangial cells, promoted cell proliferation. In parallel, the protein expression of DDIT4, TSC1/TSC2, and 4E-BP1 were decreased, and Rheb, mTOR, and p70S6K were increased. Acting via the DDIT4/mTOR signaling, 1,25(OH)2 D3 treatment reversed these pathological changes, upregulated DDIT4, TSC1/TSC2, and 4E-BP1, downregulated Rheb, mTOR, and p70S6K. The short-term overexpression of DDIT4 inhibited the proliferation of rat mesangial cells, similar to 1,25(OH)2 D3 treatment. siRNA knockdown of DDIT4 suppressed antiproliferative responses to 1,25(OH)2 D3. These results suggest that 1,25(OH)2 D3 inhibits the proliferation of rat mesangial cells induced by high glucose via the DDIT4/mTOR signaling pathway.
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