대한신장학회

Skip Navigation: Skip to contents

KOR
ENG
전체메뉴보기

간행물 검색

현재 페이지 경로

HOME
간행물
간행물 검색

논문분류	춘계학술대회 초록집
제목	The role of fumarate in the progression of membranous nephropathy: metabolomics analysis and its in-vitro validation.
저자	Hyung Ah Jo
출판정보	2018; 2018(1):
키워드	Membranous nephropathy \| Metabolomics \| Fumarate
초록	Objectives: Although pathognomonic antigens such as phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain-containing 7A (THSD7A) identified in membranous nephropathy (MN), the levels of their corresponding autoantibodies do not always predict the long-term prognosis or treatment response. We aimed to figure out biomarkers predicting the prognosis and treatment response using metabolomics analysis of urine samples. Methods: Urine samples at the time of kidney biopsy were obtained from patients with MN (n=76), minimal change disease (MCD) (n=74) and healthy controls (n=82). Metabolic profiles of the urines were analyzed by using the 800-MHz NMR-based method. An in-vitro validation study was performed using primary-cultured human podocytes treated with IgG purified from an MN patient with high PLA2R level. To characterize the role of fumarate, we conducted lentivirus-mediated fumarate hydratase activation in-vitro. Results: On the basis of metabolomics findings, in-vitro experiments using primary-cultured human podocytes were performed to validate the metabolomics analysis. Western blotting was performed using the lysates from the podocytes with purified IgG from a PLA2R-associated MN patient (MN-IgG). There was a 185-kD protein band which indicates the expression of PLA2R on the podocytes and PLA2R Ag-Ab interaction following treatment of the MN-IgG. In in-vitro experiments, the MN-IgG, but not control-IgG, increased fibronectin and SNAIL, and decreased ZO-1, WT-1 and fumarate hydratase, an enzyme that catalyzes fumarate. Meanwhile, lentivirus-mediated fumarate hydratase activation significantly abrogated the MN-IgG mediated changes in the protein expressions. Conclusions: These findings suggest that fumarate might play an important role in the progression and disease activity of MN via the regulation of podocyte integrity and renal fibrosis.
원문(PDF)	PDF 원문보기

목록

위로가기