Vitamin D upregulates endothelin-1, ETBR, eNOS mRNA expression and attenuates vascular remodelling and ischemia in kidney fibrosis model in mice.
Penulis/Author
dr. Nur Arfian, Ph.D. (1); M. HALIM HANINDYA K. (2); dr. Nungki Anggorowati, Sp.PA(K)., Ph.D. (3); Dr. Dhite Bayu Nugroho, S.Ked. MSc. PhD. (4); Agian Jeffilano (5); Yoko Suzuki (6); Koji Ikeda (7); Noriaki Emoto (8)
Tanggal/Date
23 2018
Kata Kunci/Keyword
Abstrak/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.
Rumpun Ilmu
Ilmu Kedokteran Dasar & Biomedis
Bahasa Asli/Original Language
English
Level
Internasional
Status
Dokumen Karya
No
Judul
Tipe Dokumen
Aksi
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