IFN-γ induces lipogenesis in mouse mesangial cells via the JAK2/STAT1 pathway
Abstract
The objective is to investigate the effect of high mobility group box-1 (HMGB1) on lipid deposition in γ-interferon (IFN-γ)-stimulated mouse mesangial cell line (MMC) and to determine whether the Janus kinase 2 and signal transducer and activator of transcription 1 (JAK2/STAT1) signaling pathway plays an important role in this process. We employed a control group, an IFN-γ stimulation group, and an IFN-γ + AG490 (JAK2 inhibitor) group. RNA interference aimed at sterol regulatory element-binding protein-1 (SREBP-1) or HMGB1 was used to investigate the effect of these proteins on IFN-γ-induced lipid deposition. Western blotting was used to detect phospho (p)-JAK2, JAK2, p-STAT1, STAT1, SREBP-1, fatty acid synthase (FAS), and HMGB1 protein expression. RT-PCR was used to detect SREBP-1, FAS, and HMGB1 mRNA. Oil Red O staining and the triglyceride assay were used to detect lipid deposition and triglyceride content. Results were as follows: 1) IFN-γ increased MMC cell lipid deposition, triglyceride content, and p-JAK2, p-STAT1, SREBP-1, and FAS expression; 2) SREBP-1 inhibition prevented FAS upregulation and attenuated IFN-γ-induced MMC cell lipid deposition and triglyceride content; 3) HMGB1 upregulated SREBP-1 and FAS mRNA and protein levels, which increased lipid deposition in MMC cells. Small interfering RNA-mediated inhibition of HMGB1 decreased SREBP-1 and FAS expression and lipid accumulation; 4) AG490 decreased upregulation of HMGB1 and p-JAK2/p-STAT1, as well as IFN-γ-induced lipogenesis. In conclusion, the JAK2/STAT1 pathway mediates IFN-γ-induced lipogenesis in MMC cells through regulation of HMGB1/SREBP-1/FAS.
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Between IFN-β and control conditions in all cells, the top 25 differentially active TFs, including the top-ranked SREBP, are consistent with previously reported interferon induction of lipogenesis.
“Between IFN-β and control conditions in all cells, the top 25 differentially active TFs, including the top-ranked SREBP (Supplementary Fig. 16d), are consistent with previously reported interferon induction of lipogenesis57, which has not been described in the previous scRNA-seq analysis56.”
From Transformer for one stop interpretable cell type annotation (2023) · cites this paper as [57]
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- Authors
- Hao, J., Zhang, Y.-J., Lv, X., Xu, N., Liu, Q.-J., Zhao, S., Feng, X.-J., Xing, L.-L., Kang, P.-P., Li, G.-Y., & Liu, S.-X.
- Affiliations
- Hebei Medical University (CN)
- Department of Pathology, Hebei Medical University, Hebei Key Laboratory of Nephrology, Shijiazhuang, China;
- Department of Nephrology, Second Hospital of Hebei Medical University, Shijiazhuang, China; and
- Department of Nephrology, Third Hospital of Hebei Medical University, Shijiazhuang, China
- Corresponding author
- Liu, Qin-juan
- Venue
- American Journal of Physiology-Cell Physiology
- Publisher
- American Physiological Society
- Published
- 2013-04-15
- Volume
- 304
- Issue
- 8
- Pages
- C760-C767
- ISSN
- 0363-6143 (ISSN-L)
- 1522-1563
- OpenAlex
- W2322101694
- Cited by
- 27
- References
- 30
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 4 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 2 · 2016: 3 · 2015: 2 · 2014: 2
- FWCI
- 1.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Cell Physiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- interferon-gamma, lipogenesis, mesangial cells, JAK2/STAT1 signaling, HMGB1, SREBP1, fatty acid synthase, lipid accumulation, triglyceride accumulation, diabetic nephropathy
- MeSH terms
- Animals, Cell Line, Interferon-gamma, Signal Transduction, HMGB1 Protein, Lipogenesis, Mesangial Cells, STAT1 Transcription Factor, Mice, Janus Kinase 2
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