Ask about this productRelated genes to: TGFB1I1 antibody
- Gene:
- TGFB1I1 NIH gene
- Name:
- transforming growth factor beta 1 induced transcript 1
- Previous symbol:
- -
- Synonyms:
- Hic-5, TSC-5, ARA55, HIC-5
- Chromosome:
- 16p11.2
- Locus Type:
- gene with protein product
- Date approved:
- 1998-03-23
- Date modifiied:
- 2016-10-05
Related products to: TGFB1I1 antibody
Related articles to: TGFB1I1 antibody
- Nonalcoholic steatohepatitis (NASH) is a metabolic disease characterized by hepatic steatosis and inflammation among other features. Dysregulated lipid metabolism is crucial in the pathogenesis of NASH. However, its regulatory mechanisms remain intricate and poorly elucidated. Hepatic stellate cells (HSCs) have been reported to contribute to hepatocellular lipid metabolism dysregulation and aggravate NASH progression. However, the potential mechanisms remain unclear. Here, we demonstrate that hydrogen peroxide-inducible clone 5 (Hic-5), which is highly expressed in HSCs within the liver, is elevated in NASH patients and mouse models. Hic-5 deficiency alleviates hepatic steatosis, and liver metabolomics revealed reduced fatty acid levels. Meanwhile, RNA-sequencing revealed that Hic-5 deficiency increases AMPK phosphorylation. Additionally, HSC-specific overexpression of Hic-5 exacerbates NASH severity. Co-culture experiments indicated that Hic-5 increases hepatocellular fatty acid synthesis. Cellular transcriptomic analysis and validation revealed that prostaglandin E2 (PGE2), secreted by HSCs, mediates hepatocellular fatty acid synthesis. Mechanistically, the N-terminal domain of Hic-5 binds c-Src, leading to phosphorylation of PTEN, which is bound to the C-terminal domain. This event subsequently induces phosphorylation and nuclear translocation of the transcription factor SP1, ultimately increasing PGE2 secretion. Finally, Hic-5 promotes hepatocellular fatty acid synthesis by activating the PGE2-EP4 axis. Pharmacological inhibition of EP4 in HSC-specific Hic-5 overexpression mice fed with HFD diet (HFD) significantly attenuated NASH progression. These findings increase our understanding of molecular mechanisms linking hepatic lipid metabolism dysregulation and may offer therapeutic potential for treating NASH. - Source: PubMed
Publication date: 2026/02/09
Huang ZhiweiTan PengGu BoyuanLiu ShengluLi HanChen JiatongRen BingyuSun LeiWen JianLi YuFu Wenguang - Sjögren's disease (SjD), mucosa-associated lymphoid tissue lymphoma (MALT lymphoma), and thyroid cancer (THCA) are clinically distinct yet immunologically intertwined diseases characterized by chronic inflammation and aberrant immune activation. However, the shared molecular basis linking autoimmunity and oncogenesis remains poorly defined. - Source: PubMed
Publication date: 2026/01/18
Wu GuanhaoShi JiaqiGao ChenjingChen QunZhang JingLiu Shu - Vascular remodeling, a precursor to atherosclerosis and coronary heart disease, is associated with high morbidity and mortality in individuals with diabetes. The roles of endothelial-mesenchymal transition (EndMT) and human umbilical cord mesenchymal stem cells (hUCMSCs) in this process remain unclear. In this study, we used db/db mice as a diabetic model to investigate the effect of hUCMSCs on metabolic reprogramming and vascular remodeling. We analyzed serum markers, tissue morphology, metabolomics, and endothelial cell-specific proteomics. The results demonstrated that vascular remodeling and EndMT were exacerbated in diabetes and alleviated by hUCMSCs. Metabolomic analysis identified 209 altered metabolites. Most metabolic intermediates were increased, while anti-inflammatory metabolites such as arachidonoyl ethanolamide and sphingosine were decreased in the diabetic state. Treatment with hUCMSCs restored these metabolites to near-normal levels, thereby improving metabolic reprogramming and the vascular microenvironment. Correspondingly, endothelial cell proteomics revealed increased levels of glycolytic enzymes, inflammatory factors, and EndMT markers, including mitogen-activated protein kinase kinase kinase 20 (Map3k20), disintegrin and metalloproteinase domain-containing protein 10 (Adam10), and integrin alpha-8 (Itga8), in diabetes; hUCMSC treatment downregulated these factors. Notably, KEGG and protein-protein interaction analyses indicated that hUCMSCs inhibited the Tgfb1i1/Rock1 axis within the TGF-beta pathway, which drives EndMT. We further verified the expression of these proteins through endothelial immunofluorescent co-staining and confirmed the role of Rock1 in high glucose-induced EndMT in vitro. This study elucidates a potential molecular mechanism and a therapeutic strategy for early atherosclerosis in diabetes and provides a foundation for evaluating endothelial states in vivo. - Source: PubMed
Ling MingyingHe JingxianJia XuYu NaSong YipingLi XuehuiTang CongminYu WenzhuoQiao HanZhang ChenglongZhang ZhenMa TianminZhao ChuanliXing Yanqiu - Mechanical forces are essential for organ function, but excessive or dysregulated forces can promote pathologic conditions. In asthma, bronchoconstriction narrows the airway, compressing the airway epithelium and activating mechanotransduction, yet key regulators of mechanotransduction remain unclear. Here we show that Hic-5, a focal adhesion adaptor, is a key regulator of epithelial mechanotransduction. In human airway epithelial cells at air-liquid interface exposed to mechanical compression that mimics bronchoconstriction, we find that compression induces Hic-5 expression in airway basal cells. We further validated these in vitro findings by reanalyzing single-cell RNA-seq data from patients with asthma undergoing bronchoconstriction after allergen challenge, which revealed increased Hic-5 expression in airway basal cells. Hic-5 knockdown in human airway epithelial cells markedly attenuates mechanoresponses to compression, including stress fiber formation, differential gene expression, and increased secretion of endothelin-1 (ET-1). Through secretion of ET-1, a potent bronchoconstrictor, Hic-5 drives epithelial mechanotransduction and promotes a feed-forward cycle of bronchoconstriction, thereby highlighting dysregulated mechanical forces as active drivers of human disease. - Source: PubMed
Publication date: 2025/12/12
Mwase ChimwemweDeng WenjiangKim Hyo JinMitchel Jennifer APhung Thien-KhoiO'Sullivan Michael JMathews Joel ACrosby JeffreyTurner Christopher EHaber Adam LPark Jin-Ah - The global prevalence of type 2 diabetes mellitus (T2DM) continues to rise. Therefore, it has become a major concern health issue worldwide. T2DM leads to various complications, including metabolic-associated fatty liver disease (MAFLD). However, comprehensive studies on MAFLD as a diabetic complication at different stages are still lacking. Using advanced single-cell RNA-seq technology, we explored changes of livers in two T2DM murine models. Our findings revealed that increase activation of hepatic stellate cells (HSCs) exacerbated the development of MAFLD to steatohepatitis by upregulating transforming growth factor β1 induced transcript 1 (). Upregulated thioredoxin-interacting protein () contributed to hepatocyte damage by impairing reactive oxygen species clearance. Additionally, the capillarization of liver sinusoidal endothelial cells correlated with overexpression in endothelial cells. A novel subset of Kupffer cells (KCs) that expressed exhibited an activated phenotype, potentially participating in inflammation in the liver of diabetic mice. Furthermore, ligand-receptor pair analysis indicated that activated HSCs interacted with hepatocytes or KCs through and in late-stage diseases. The reduction in cell-cell interactions within hepatocytes in diabetic mice, reflects that the mechanisms regulating liver homeostasis is disrupted. This research underscores the importance of dynamics in diabetic MAFLD, and provides new insights for targeted therapies. - Source: PubMed
Publication date: 2024/10/14
Dai Chia-YenTsai Ying-MingChang Chao-YuanTsai Hung-PeiWu Kuan-LiWu Yu-YuanWu Ling-YuJian Shu-FangTsai Pei-HsunOng Chai-TungSun Chien-HuiHsu Ya-Ling