Ask about this productRelated genes to: HNF4A Blocking Peptide
- Gene:
- HNF4A NIH gene
- Name:
- hepatocyte nuclear factor 4 alpha
- Previous symbol:
- TCF14, MODY, MODY1
- Synonyms:
- NR2A1, HNF4
- Chromosome:
- 20q13.12
- Locus Type:
- gene with protein product
- Date approved:
- 1998-04-20
- Date modifiied:
- 2019-04-23
Related products to: HNF4A Blocking Peptide
Related articles to: HNF4A Blocking Peptide
- We report the case of a pregnant woman with coexisting pathogenic hepatocyte nuclear factor 4 alpha ( and insulin receptor ( gene variants. A 25-year-old lean Caucasian gravida 1, para 0 (G1P0) woman with a history of early-onset diabetes and features of insulin resistance, was referred at 6 weeks' gestation. Molecular testing confirmed pathogenic variants in and . Noninvasive prenatal testing predicted fetal inheritance of the variant. Despite good maternal glycemic control and relatively low insulin requirements, the infant was macrosomic and developed persistent postnatal hypoglycemia requiring prolonged diazoxide therapy. This case highlights the importance of early recognition of monogenic diabetes in pregnancy, the potential utility of noninvasive prenatal testing, and the observation of persistent hyperinsulinemia beyond the neonatal period in -related diabetes. - Source: PubMed
Publication date: 2026/04/29
Wu KatherineRussell HamishRodrigo Natassia - The CCR4-NOT complex is a central regulator of post-transcriptional gene expression that controls mRNA deadenylation and decay. Although the catalytic subunits have been well characterized, the physiological roles of several non-catalytic subunits including CNOT11 in mammalian tissues remain incompletely understood. Here, we investigate the physiological role of CNOT11 using genetic mouse models. No homozygous global Cnot11 knockout mice are obtained from heterozygous intercrosses, indicating that CNOT11 is required for early development. We generate hepatocyte-specific Cnot11 knockout mice (Cnot11-LKO) and find that Cnot11-LKO mice exhibit growth retardation and alterations in serum biochemical parameters during early postnatal stages, which are largely resolved by adulthood. Histological analysis does not reveal overt liver injury, while morphological differences in hepatocytes are observed. A marked increase in Ki67-positive cells was observed in the liver of Cnot11-LKO mice relative to control mice. Most Ki67-positive cells express HNF4A, suggesting that hepatocyte maturation is still in progress in the absence of CNOT11. Transcriptomic analyses of early postnatal livers reveal increased expression of cell cycle-related genes and reduced expression of metabolic genes, further supporting delayed liver maturation. These findings suggest that CNOT11 contributes to proper postnatal liver maturation and is required for the timely establishment of metabolically mature hepatocyte functions. - Source: PubMed
Nishijima SaoriSuzuki ToruAbe TakayaBando KanaYamamoto Tadashi - The biogenesis and transport of lipoproteins are essential for systemic homeostasis and cardiometabolic health, yet how the secretory pathway acquires specialization to support high-capacity lipoprotein export remains unclear. Here, we report SEC16B as a tissue-selective modulator of the COPII machinery, critical for the efficient secretion of APOB-containing lipoproteins. Integrative bioinformatic analyses identify that SEC16B co-emerges with core genes involved in lipoprotein biogenesis. Functional studies, coupled with AI-driven prediction, reveal that SEC16B acts as a molecular brake to fine-tune COPII condensation for lipoprotein export. Mining of UK biobank data links SEC16B to metabolic traits in humans and suggests HNF4A-dependent regulation of SEC16B expression. Hepatic deletion of SEC16B in mice markedly reduces circulating APOB, triglycerides and cholesterol, while conferring robust protection against atherosclerosis and cardiac dysfunction and maintaining liver health. Collectively, these findings position SEC16B as a specialized modulator of lipoprotein export via the general secretory (SEC) pathway in the liver, suggesting potential therapeutic avenues for combating cardiometabolic diseases. - Source: PubMed
Publication date: 2026/04/24
Wang XiaoHu YatingLiu LuHuang RunzeWang YaweiLiu BingZhao YifeiZhu YuangangLv JiaLiu LiangWang HuiminWu LingzhiXu XinxuanLi YaxinWang GuanlinChen Xiao-Wei - Secreted phosphoprotein 2 (SPP2), also known as SPP24, is a secreted protein belonging to the cystatin superfamily. Initially identified as a regulator of bone metabolism via the BMP signaling pathway, SPP2 has recently been implicated in liver pathophysiology, where it suppresses hepatocellular carcinoma and negatively regulates liver regeneration. However, whether SPP2 responds to other physiological cues or plays a direct role in metabolic regulation has remained unknown. Here, we demonstrate that both recombinant SPP2 protein and AAV8-mediated SPP2 overexpression selectively reduce serum triglyceride (TG) levels without affecting other metabolic parameters. Mechanistically, SPP2 reduces serum TG by promoting VLDL hydrolysis through enhanced LPL activity, which it achieves via direct binding to LPL and modulation of LPL cofactor expression. In addition to its role in TG clearance, SPP2 promotes hepatic fatty acid β-oxidation and ketogenesis, supporting energy production during fasting. Notably, SPP2 expression and secretion are induced upon fasting. This induction is mediated by fasting-induced free fatty acid (FFA) mobilization, which activates hepatocyte nuclear factor 4 alpha (HNF4A), a nutrient-sensing nuclear receptor that binds fatty acids. HNF4A directly binds to the SPP2 promoter, and pharmacological activation of HNF4A increases SPP2 expression, establishing HNF4A as a key regulator of this response. Together, these findings establish an HNF4A-SPP2 axis that responds to fasting and uncover a previously unrecognized role for SPP2 in triglyceride reduction, positioning it as a potential therapeutic candidate for hypertriglyceridemia. - Source: PubMed
Publication date: 2026/04/15
Wen YutingLiu XiaoyuWang MingjunLi Changying - The inflammation-intestinal metaplasia (IM)-carcinoma cascade has been proposed as a framework for gastric cancer (GC) development, yet the cell-level heterogeneity and microenvironmental remodeling underlying this progression remain poorly characterized. Here, we constructed a single-cell transcriptomic atlas by integrating scRNA-seq data from chronic gastritis (superficial, CGS), IM, cancer-adjacent, and tumor tissues through a unified analytical pipeline. Seven major cell lineages were resolved. Relative to CGS, IM and GC tissues exhibited a progressive contraction of epithelial compartments accompanied by expansion of immune and stromal populations. Copy number variation (CNV) inference identified two tumor-restricted malignant epithelial subgroups-one biased toward differentiation and the other enriched for inflammatory and epithelial-mesenchymal transition (EMT) signatures-as well as putative proto-malignant intermediates that coexisted with phenotypically normal epithelium. Cell-cell communication analysis indicated broadly augmented crosstalk between epithelial cells and T cells, myeloid cells, and fibroblasts, with prominent involvement of a CD44-extracellular matrix (ECM) axis. Pseudotime trajectory analysis placed malignant epithelium at late positions along gastric and pyloric mucosal cell differentiation backbones, coinciding with increasing CNV burden and enrichment of stem-like transcriptional programs. Gene regulatory network analysis revealed coordinated activity of lineage-specification modules (HNF4/CDX, NR1H4/ESRRA), proliferative regulons (MYC/TFDP1), and inflammatory/EMT-associated programs (FOSL1/REL/NF-κB). In independent cohorts, elevated expression of several malignant-epithelium-associated transcription factors-including HNF4A, KLF3, FOSL1, TCF7L2, BCL3, RELB, ONECUT2, and MAF-correlated with unfavorable overall survival. Collectively, these findings provide single-cell-resolution evidence consistent with the proposed three-stage model of gastric carcinogenesis and highlight candidate transcriptional regulators warranting further investigation as potential early-detection biomarkers. - Source: PubMed
Publication date: 2026/04/22
Li XiulanGuo MengqiWen YunhanLong Bo