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[HMGB1/SREBP-1 mediated IFN-gamma-induced lipid deposition in mouse mesangial cells]
Yu-Jun Zhang1, Yan-Ning Chen, Shu-Shen Zheng
1Department of Pathology, Hebei Medical University, Shijiazhuang 050017, China.
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.
Insights
Interferon-gamma (IFN-gamma) induces lipid deposition in mouse mesangial cells by increasing High Mobility Group Box 1 (HMGB1) and Sterol Regulatory Element-Binding Protein-1 (SREBP-1) expression. This pathway highlights a potential therapeutic target for lipid accumulation disorders.
Area of Science:
- Cell Biology
- Molecular Biology
- Immunology
Context:
- Lipid deposition in mesangial cells is implicated in kidney disease progression.
- Interferon-gamma (IFN-gamma) is a pro-inflammatory cytokine with poorly understood roles in lipid metabolism.
- Understanding the molecular mechanisms of IFN-gamma-induced lipogenesis is crucial for developing targeted therapies.
Purpose:
- To elucidate the mechanism by which IFN-gamma stimulates lipid deposition in mouse mesangial cells (MMC).
- To investigate the role of High Mobility Group Box 1 (HMGB1) and Sterol Regulatory Element-Binding Protein-1 (SREBP-1) in IFN-gamma-mediated lipogenesis.
Summary:
- IFN-gamma treatment led to significant lipid droplet accumulation in MMC.
- IFN-gamma upregulated the expression of HMGB1, SREBP-1, and fatty acid synthetase (FAS) mRNA and protein in a time-dependent manner.
- Silencing HMGB1 or SREBP-1 suppressed IFN-gamma-induced lipid deposition, confirming their critical roles in this process.
Impact:
- This study identifies the HMGB1/SREBP-1/FAS signaling pathway as a key mediator of IFN-gamma-induced lipid deposition in mesangial cells.
- Findings suggest that targeting this pathway could offer a novel therapeutic strategy for managing kidney diseases associated with aberrant lipid metabolism.
- Provides a molecular basis for the interplay between inflammation and lipid accumulation in renal pathology.
