Vitamin D upregulates endothelin-1, ETBR, eNOS mRNA expression and attenuates vascular remodelling and ischemia in kidney fibrosis model in mice

N. Arfian, M. H.H. Kusuma, N. Anggorowati, D. B. Nugroho, A. Jeffilano, Y. Suzuki, K. Ikeda, N. Emoto

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

We examined the upregulation of ET-1/ETBR/eNOS signaling in renoprotective effect of vitamin D in kidney fibrosis model in mice using unilateral ureteral obstruction (UUO). One group was treated with intraperitoneal injection of 0.125 mg/kg of Calcitriol (UUO+VD). Vascular remodeling was quantified based on lumen area and lumen/wall area ratio (LWAR) of intrarenal arteries using Sirius Red staining. ET-1, ETBR, eNOS, CD31 and VEGF mRNA expressions were quantified using qRT-PCR. Focusing on endothelin-1 (ET-1) signaling in endothelial cells (EC), siRNA of ET-1 was performed in human umbilical vein endothelial cells (HUVEC) for reducing ET-1 expression. Then HUVECs were treated with and without 100 nM Calcitriol treatment in hypoxic and normoxic conditions to elucidate ET-1/eNOS signaling. Our in vivo study revealed vascular remodeling and renal ischemia attenuation after Calcitriol treatment. Vascular remodeling was attenuated in the UUO+VD group as shown by increasing lumen areas and LWAR in intrarenal arteries. These findings were associated with significant higher CD31 and VEGF mRNA expression compared to the UUO group. Vitamin D treatment also increased ET-1, ETBR and eNOS mRNA expressions. Our in vitro study demonstrated Calcitriol induced ET-1 and eNOS mRNA expressions upregulation in HUVEC under normoxic and hypoxic condition. Meanwhile, siRNA for ET-1 inhibited the upregulation of eNOS mRNA expression after Calcitriol treatment. Vitamin D ameliorates kidney fibrosis through attenuating vascular remodeling and ischemia with upregulating ET-1/ETBR and eNOS expression.

Original languageEnglish
Pages (from-to)S137-S147
JournalPhysiological Research
Volume67
DOIs
Publication statusPublished - 2018

Keywords

  • Endothelin-1
  • eNOS
  • Kidney fibrosis
  • Vascular remodeling
  • Vitamin D

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