[HMGB1/SREBP-1 mediated IFN-gamma-induced lipid deposition in mouse mesangial cells].

Objective: To explore the possible mechanism of lipid deposition induced by interferon-gamma (IFN-gamma).

Methods: The mouse mesangial cells (MMC) were randomly divided into control group, stimulation group, stimulation + control vector group (sh-HMGB1) and stimulation+ specific sh-vector group (sh-SREBP-1). RT-PCR was used to detect the expression of HMGB1, SREBP-1 and fatty acid synthetase (FAS) mRNA; the protein expression was determined by Western blot.

Results: The Oil Red O staining revealed that the mouse mesangial cells showed significant lipid droplet in IFN-gamma group. IFN-gamma up-regulated the expression of HMGB1, SREBP-1, FAS mRNA and protein time-dependently; Transfection of MMC with HMGB1 siRNA resulted in the suppression of SREBP-1, FAS protein levels induced by IFN-gamma, following with decrease of lipid deposition. Stimulation with HMGB1 markedly induced expression of SREBP-1, FAS expression and peaked at 8 h, decreased at 12 h compared with that at 8 h. Sh-SREBP-1 decreased the lipid deposition induced by HMGB1 in MMC.

Conclusion: IFN-gamma might induce lipid deposition in mouse mesangial cells partly by up-regulating the expression of HMGB1/SREBP-1/FAS.