Cited by 27Cytokine Signaling Pathways and InteractionsCancer, Lipids, and MetabolismLipid metabolism and biosynthesis

IFN-γ induces lipogenesis in mouse mesangial cells via the JAK2/STAT1 pathway

Hao, Jun, Zhang, Yu-jun, Lv, Xin, Xu, Ning, Liu, Qin-juan, Zhao, Song, Feng, Xiao-juan, Xing, Ling-ling +3 more·2013·American Journal of Physiology-Cell Physiology

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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Crossref · 10.1152/ajpcell.00352.2012

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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
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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