Direct effects of 25-hydroxyvitamin D on renal fibrosis

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461227
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Osaka University
• Principal Investigator: Matsui Isao 大阪大学, 医学系研究科, 助教 (60456986)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 25(OH)D / 腎尿細管間質線維化 / ビタミンD

Outline of Final Research Achievements

Effects of 25(OH)D3 on unilateral ureteral obstruction were analyzed. Excess 25(OH)D3 in obstructed mice worsened oxidative stress and tubulointerstitial fibrosis, whereas moderate levels of 25(OH)D3 had no effects. The exacerbating effects of excess 25(OH)D3 were abolished in CYP27B1/VDR double-knockout mice and in macrophage-depleted CYP27B1 knockout mice. Excess 25(OH)D3 upregulated both M1 marker (TNF-α) and M2 marker (TGF-β1) levels of kidney-infiltrating macrophages. In vitro analyses verified that excess 25(OH)D3 directly upregulated TNF-α and TGF-β1 in cultured macrophages but not in tubular cells. TNF-α and 25(OH)D3 cooperatively induced oxidative stress by upregulating iNOS in tubular cells. Aggravated tubulointerstitial fibrosis in mice with excess 25(OH)D3 indicated that macrophage-derived TGF-β1 also had a key role in the pathogenesis of surplus 25(OH)D3. Thus, excess 25(OH)D3 worsens tubulointerstitial injury by modulating macrophage phenotype.

Free Research Field

腎臓