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- Title
TWIST2 and the PPAR signaling pathway are important in the progression of nonalcoholic steatohepatitis.
- Authors
Zhang, Yanmei; Ge, Xiaoxiao; Li, Yongqing; Zhang, Bingyang; Wang, Peijun; Hao, Mingju; Gao, Peng; Zhao, Yueyi; Sun, Tao; Lu, Sumei; Ma, Wanshan
- Abstract
Background: To investigate the roles of the transcription factors twist family bHLH transcription factor 1 (TWIST1), twist family bHLH transcription factor 2 (TWIST2), and peroxisome proliferator activated receptor gamma (PPARγ) in the progression of nonalcoholic steatohepatitis. Methods: The protein levels of TWIST1, TWIST2 and PPARγ were determined in the serum of nonalcoholic fatty liver disease (NAFLD) patients and healthy controls by enzyme-linked immunosorbent assay (ELISA). An in vivo model for fatty liver was established by feeding C57BL/6 J mice a high-fat diet (HFD). An in vitro model of steatosis was established by treating LO-2 cells with oleic acid (OA). RNA sequencing was performed on untreated and OA-treated LO-2 cells followed by TWIST1, TWIST2 and PPARγ gene mRNA levels analysis, Gene Ontology (GO) enrichment and pathway analysis. Results: The TWIST2 serum protein levels decreased significantly in all fatty liver groups (P < 0.05), while TWIST1 varied. TWIST2 tended to be lower in mice fed an HFD and was significantly lower at 3 months. Similarly, in the in vitro model, the TWIST2 protein level was downregulated significantly at 48 and 72 h after OA treatment. RNA sequencing of LO-2 cells showed an approximately 2.3-fold decrease in TWIST2, with no obvious change in TWIST1 and PPARγ. The PPAR signaling pathway was enriched, with 4 genes upregulated in OA-treated cells (P = 0.0018). The interleukin (IL)-17 and tumor necrosis factor (TNF) signaling pathways were enriched in OA-treated cells. Conclusions: The results provide evidence that the TWIST2 and PPAR signaling pathways are important in NAFLD and shed light on a potential mechanism of steatosis.
- Subjects
BLOOD proteins; PEROXISOME proliferator-activated receptors; FATTY liver; TUMOR necrosis factors; TRANSCRIPTION factors; ENZYME-linked immunosorbent assay
- Publication
Lipids in Health & Disease, 2021, Vol 20, Issue 1, p1
- ISSN
1476-511X
- Publication type
Article
- DOI
10.1186/s12944-021-01458-0