Calcitriol attenuates vascular remodeling in association with alteration of ppET-1/ETB R/eNOS and ETA R expression in acute and chronic phases of kidney ischemia–reperfusion injury in mice

Desita, Eryna Ayu Nugra and Arfian, Nur and Setyaningsih, Wiwit Ananda Wahyu and Sari, Dwi Cahyani Ratna (2023) Calcitriol attenuates vascular remodeling in association with alteration of ppET-1/ETB R/eNOS and ETA R expression in acute and chronic phases of kidney ischemia–reperfusion injury in mice. Canadian Journal of Physiology and Pharmacology, 101 (1). 8 – 17. ISSN 00084212

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Abstract

Kidney ischemia–reperfusion injury (IRI) causes acute kidney injury with increasing risk of maladaptive repair through endothelin-1 (ET-1)/endothelin type A receptor (ETA R) signaling. Calcitriol shows renoprotection in kidney fibrosis, however, its effects on vasoactive substances expression and vascular remodeling following kidney IRI remain unclear. This research aimed to investigate Calcitriol’s effects on preproendothelin-1 (ppET-1), ETA R, endothelial nitric oxide synthase (eNOS) mRNA expression and vascular remodeling in acute and chronic phases of kidney IRI in mice. Twenty-five male Swiss mice were randomly divided into five groups (n = 5): SO (sham-operated), IR3 (3 day kidney IRI), IR12 (12 day kidney IRI), IRD3 (3 day kidney IRI + Calcitriol 0.5 μg/kg body weight (BW)/day), and IRD12 (12 day kidney IRI + Calcitriol 0.5 μg/kg BW/day). Ischemia– reperfusion injury groups underwent bilateral renal pedicles clamping for 30 min, then reperfusion. Kidneys were harvested for Sirius Red staining to observe interstitial fibrosis and vascular remodeling, polymerase chain reaction to quantify ppET-1, endothelin type B receptor (ETB R), eNOS mRNA expression, and Western blotting to quantify ETA R protein expression. Calcitriol treatment in both phases of kidney IRI showed lower serum creatinine and ETA R protein expression, while higher eNOS and ETB R mRNA expression than IRI-only groups. Furthermore, ppET-1 mRNA expression was higher in IRD3 than IR3, but lower in IRD12 than IR12. Calcitriol also prevented vascular remodeling as indicated by lower wall thickness and higher lumen/wall area ratio than IRI-only groups. © 2022 The Author(s).

Item Type: Article
Additional Information: Cited by: 0
Uncontrolled Keywords: Acute Kidney Injury; Animals; Calcitriol; Endothelin-1; Fibrosis; Kidney; Male; Mice; Nitric Oxide Synthase Type III; Receptor, Endothelin A; Reperfusion Injury; RNA, Messenger; Vascular Remodeling; calcitriol; endothelial nitric oxide synthase; endothelin 1; endothelin A receptor; endothelin B receptor; messenger RNA; preproendothelin 1; calcitriol; endothelial nitric oxide synthase; endothelin 1; endothelin A receptor; messenger RNA; adult; animal experiment; animal model; animal tissue; Article; body weight; comparative study; controlled study; creatinine blood level; disease association; DNA synthesis; electrophoresis; gene amplification; gene expression; histopathology; kidney tissue; male; membrane transport; mouse; mRNA expression level; nonhuman; peritoneal cavity; polymerase chain reaction; protein expression; protein function; real time polymerase chain reaction; renal artery; renal ischemia reperfusion injury; renal protection; reverse transcription polymerase chain reaction; RNA extraction; Swiss Webster mouse; thoracic cavity; tissue preservation; vascular remodeling; Western blotting; acute kidney failure; animal; fibrosis; genetics; kidney; metabolism; reperfusion injury; vascular remodeling
Subjects: R Medicine > RB Pathology
Divisions: Faculty of Medicine, Public Health and Nursing > Biomedical Sciences
Depositing User: Sri JUNANDI
Date Deposited: 01 Nov 2024 02:27
Last Modified: 01 Nov 2024 02:27
URI: https://ir.lib.ugm.ac.id/id/eprint/6105

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