TLR2 Plays a Critical Role in HMGB1-Induced Glomeruli Cell Proliferation Through the FoxO1 Signaling Pathway in Lupus Nephritis

Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research
Xiao-Juan FengShuxia Liu

Abstract

The objective of this study was to examine the role and possible mechanisms of toll-like receptor 2 (TLR2) in high-mobility group box chromosomal protein 1 (HMGB1)-induced mouse mesangial cell (MMC) proliferation and glomeruli proliferation of MRL/Fas(lpr) mice. First, the expression of proliferating cell nuclear antigen (PCNA), TLR2 and Forkhead box protein O1 (FoxO1) messenger RNA (mRNA) and protein in the glomeruli of MRL/Fas(lpr) mice was quantified, and the correlation with cell proliferation of glomeruli was analyzed. Then, lipopolysaccharide (LPS), TLR2 neutralization antibody, and small hairpin TLR2 (shTLR2) were used to confirm the role of TLR2 in HMGB1-induced MMC proliferation. Furthermore, wild-type FoxO1 (WT-FoxO1) vector was used to investigate the effect of FoxO1 pathway on HMGB1-induced MMC proliferation. Finally, electroporation was used to knockdown TLR2 in the glomeruli of MRL/Fas(lpr) mice, and renal function, FoxO1, and PCNA expression were detected. The results showed that the TLR2 expression was upregulated and FoxO1 expression was decreased in the glomeruli of MRL/Fas(lpr) mice, and these effects were significantly correlated with cell proliferation of the glomeruli. In vitro, the TLR2 neutralization ant...Continue Reading

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Citations

Feb 15, 2018·Clinical Science·Dolores OlivaresRaquel Cortes
Jan 24, 2018·American Journal of Physiology. Renal Physiology·Kamala SundararajTamara K Nowling
Apr 14, 2018·Journal of Biomedical Science·Satish Kumar Devarapu, Hans-Joachim Anders
Nov 2, 2019·Journal of Cellular Physiology·Xiaojuan FengShuxia Liu
Jun 5, 2019·Current Medicinal Chemistry·Qian RenPing Fu

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Methods Mentioned

BETA
transfection
PCR
electrophoresis
nuclear translocation

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