title: 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.
authors: Department of Pathology, Hebei Medical University, Hebei Key Laboratory of Nephrology, Shijiazhuang, China.
authors: Jun
authors: J
authors: Hao
authors: Yu-jun
authors: YJ
authors: Zhang
authors: Xin
authors: X
authors: Lv
authors: Ning
authors: N
authors: Xu
authors: Qin-juan
authors: QJ
authors: Liu
authors: Song
authors: S
authors: Zhao
authors: Xiao-juan
authors: XJ
authors: Feng
authors: Ling-ling
authors: LL
authors: Xing
authors: Peng-peng
authors: PP
authors: Kang
authors: Gui-ying
authors: GY
authors: Li
authors: Shu-xia
authors: SX
authors: Liu
mesh_terms: D000818:Animals; D002460:Cell Line; D024243:HMGB1 Protein / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000502:physiology*; D053614:Janus Kinase 2 / Q000096:biosynthesis*; D050155:Lipogenesis / Q000502:physiology*; D050527:Mesangial Cells / Q000378:metabolism*; D051379:Mice; D050794:STAT1 Transcription Factor / Q000096:biosynthesis*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D024243:HMGB1 Protein; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D007371:Interferon-gamma; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2