Heat-aggregated gamma globulins suppress autophagy and induce injuries in glomerular endothelial cells

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Abstract

Background: Lupus nephritis is a common and severe complication of systemic lupus erythematosus characterized by renal function impairment. Immune complex plays an important role in disease pathogenesis and organ injury. However, the precise mechanism by which immune complex leads to organ injury is still unknown. Glomerular filtration barrier (GFB) is the structural foundation of renal function and glomerular endothelial cell (GEC) is one of the three components of GFB. As autophagy is a conserved metabolic process and shows protective role in many cell types and biologic processes, we hypothesize that immune complex may suppress autophagy in GECs and participate in endothelial cell injuries and dysfunction.||Methods: We used heat-aggregated gamma globulin (HAGG) to substitute immune complex. Monomeric IgG was used as negative control. GECs were incubated with different concentrations of HAGG and collected at different time periods. Protein related to autophagy, including LC3, p62, mTOR, p70s6k, 4E-BP-1, were measured by western blotting. Cell viability and eNOS expression were detected to evaluate endothelial cell functions. Autophagy regulators were used to investigate the role of autophagy in endothelial cell injury.||Results: HAGG led to reduced ratio of LC3 II/I and increased p62 expression in GECs. Elevated expressions of p-mTOR and its substrates p-4E-BP-1 and p-p70s6k were detected. Autophagy inducer, rapamycin, could increase p-eNOS expression in GECs, while HAGG stimulation alleviated such increase. Rapamycin slightly decreased cell number, while co-incubated with HAGG further decreased cell number.||Conclusion: Our results implied that HAGG suppressed autophagy in GECs through the mTOR-dependent pathway. HAGG decreased cell viability and eNOS expression in GECs. Suppressed autophagy induced by HAGG may provide new insights in explaining the mechanism of renal impairment in lupus nephritis.
Original languageEnglish
JournalHong Kong Journal of Nephrology
Volume17
Issue number2
DOIs
Publication statusPublished - 2015

ASJC Scopus subject areas

  • Nephrology

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