Title:GDF15 Interference Regulates Proliferation, Inflammation, and Autophagy
of Lipopolysaccharide-induced Mesangial Cells by Inhibiting PI3K/
AKT/mTOR Signaling
Volume: 24
Issue: 9
Author(s): Zhen Chen, Liping Gao, Cailing Li and Wenzhu Sun*
Affiliation:
- Department of Nephrology, Shen Zhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, 518067, China
Keywords:
Chronic glomerulonephritis, GDF15, PI3K/AKT/mTOR signaling, autophagy, proliferation, ELISA, inflammation.
Abstract:
Background: Chronic glomerulonephritis (CGN) is a primary glomerular disease. As
a circulating protein, growth and differentiation factor 15 (GDF15) participates in a variety of
biological processes.
Objective: We aimed to investigate the role of GDF15 in CGN.
Methods: HBZY-1 cells were induced by lipopolysaccharide (LPS). Cell viability was detected
using a cell counting kit-8 (CCK-8) assay, and a western blot was applied for the detection of
GDF15 protein expression. After GDF15 silencing, cell proliferation was evaluated by CCK-8
assay and 5-ethynyl-2'-deoxyuridine (EDU) staining. Enzyme-linked immunosorbent assay
(ELISA) kits were used to detect the levels of inflammatory cytokines. Autophagy was assessed
by GFP-LC3B assay. Besides, the expression of NF-κB signaling-, autophagy- (LC3II/I, Beclin
l and p62) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of
rapamycin (mTOR) signaling-related proteins were measured by western blot. Afterwards,
PI3K agonist 740Y-P was used to clarify whether GDF15 affected LPS-induced HBZY-1 cells
via PI3K/AKT/mTOR signaling.
Results: LPS induction increased cell viability and elevated GDF15 expression in HBZY-1
cells. After GDF15 expression depletion, the increased proliferation of LPS-induced HBZY-1
cells was decreased. Additionally, GDF15 knockdown suppressed the release of inflammatory
factors in LPS-induced HBZY-1 cells and activated autophagy. Moreover, the PI3K/AKT/
mTOR signal was evidenced to be activated by GDF15 deficiency. The further addition of
740Y-P reversed the impacts of GDF15 deficiency on the proliferation, inflammation, and autophagy
of LPS-induced HBZY-1.
Conclusion: Collectively, GDF15 downregulation could protect against CGN via blocking
PI3K/AKT/mTOR signaling.
