대한신장학회

Skip Navigation: Skip to contents

KOR
ENG
전체메뉴보기

간행물 검색

현재 페이지 경로

HOME
간행물
간행물 검색

논문분류	춘계학술대회 초록집
제목	Lipocalin-2 promotes cardiovascular calcification in chronic kidney disease by upregulating NCOA4-mediated ferritinophagy and ferroptosis through STAT3 signaling activation
저자	Yujia Wang
출판정보	2024; 2024(1):
키워드
초록	Objectives: Cardiovascular calcification (CVC) is an insidious complication of chronic kidney disease (CKD), contributing to the high cardiovascular morbidity and mortality seen in this population. Recent evidence implicates ferroptosis, a form of programmed cell death, and ferritinophagy, particularly involving nuclear receptor coactivator 4 (NCOA4), in the pathogenesis of CKD-CVC. Lipocalin-2 (LCN2), an iron-modulating protein linked to osteogenesis and ferroptosis, has emerged as a potential contributor to CKD-CVC, yet its role remains to be fully elucidated. Methods: To assess the involvement of LCN2 in CKD-CVC, a cross-sectional clinical study evaluated its expression in patient serum and calcified arteries. Animal models, including LCN2 knockout mice and mice with VSMC-targeted LCN2 manipulation, were fed a high adenine and phosphate diet to induce CKD-CVC. In vitro, VSMCs underwent LCN2-related treatments to delineate its function. Calcification was assessed using von-Kossa and Alizarin Red staining, while molecular changes were analyzed through PCR, western blotting, and other biochemical assays. Results: LCN2 expression was positively associated with the severity of CKD-CVC. Dietary induction of CKD-CVC in vivo led to significant renal and cardiovascular calcification. In vitro, exposure to a high phosphate medium resulted in VSMC calcification and osteogenic differentiation, alongside enhanced ferroptosis indicators, such as increased iron accumulation and oxidative stress. Inhibiting ferroptosis pharmacologically reversed these effects. LCN2 knockout mice exhibited less calcification, suggesting a causative role of LCN2 in CKD-CVC. Mechanistically, LCN2 influenced NCOA4 and FTH1 expression levels, implicating ferritinophagy in the calcification process, with NCOA4 knockdown ameliorating the effects. Conclusions: LCN2 is involved in the pathophysiology of CKD-CVC via modulation of VSMC ferroptosis and osteogenic differentiation. Targeting the LCN2/STAT3/NCOA4/FTH1 axis could offer a promising therapeutic strategy for managing CKD-CVC.
원문(PDF)	PDF 원문보기

목록

위로가기