Ask about this productRelated genes to: ARNT antibody
- Gene:
- ARNT NIH gene
- Name:
- aryl hydrocarbon receptor nuclear translocator
- Previous symbol:
- -
- Synonyms:
- HIF-1beta, bHLHe2
- Chromosome:
- 1q21.3
- Locus Type:
- gene with protein product
- Date approved:
- 1990-01-22
- Date modifiied:
- 2016-10-05
Related products to: ARNT antibody
Related articles to: ARNT antibody
- The aryl hydrocarbon receptor (AHR) and the vitamin D receptor (VDR) were long regarded as independent transcription factors governing distinct physiology-xenobiotic sensing and calcium-vitamin D homeostasis, respectively. AHR, a basic helix-loop-helix/PAS protein, heterodimerizes with ARNT and binds xenobiotic response elements (XREs) to drive cytochrome P450 genes such as ; VDR, a nuclear receptor activated by 1,25-dihydroxyvitamin D, heterodimerizes with RXR and binds vitamin D response elements (VDREs). Although their genes reside on separate chromosomes (, Chr 7; , Chr 12), an integrated view recognizes the two pathways as extensively cross-regulatory. This review synthesizes the molecular, immunological, and tissue-level evidence for VDR-AHR interplay. At the molecular level, the receptors cooperate at composite promoter architectures-most notably an everted-repeat VDRE positioned adjacent to an XRE in the promoter-while AHR ligands reciprocally enhance -mediated catabolism of active vitamin D. Tryptophan metabolism provides a bidirectional hub: kynurenine and the UVB photoproduct FICZ serve as endogenous AHR ligands whose balance, modulated by VDR, shapes signaling output. The tumor suppressor p53 functions as a shared upstream regulator coupling genotoxic stress to both receptors, with convergence on the (p21) checkpoint. Functionally, AHR and VDR converge on the regulatory T cell (Treg)/Th17 axis to influence immune tolerance: sustained AHR activation by TCDD favors Foxp3 Treg differentiation, transient FICZ-driven activation promotes Th17 responses, and VDR reinforces the tolerogenic arm while independently repressing IL-17. The receptors further cooperate in maintaining intestinal epithelial barrier integrity and NF-κB restraint, with parallel impairment in inflammatory bowel disease, and are co-activated in skin by solar UVB, which simultaneously generates vitamin D and the AHR ligand FICZ within keratinocytes. In cancer, VDR acts as a tumor suppressor, AHR exhibits context-dependent pro- and anti-tumor roles, and a three-way AHR-VDR-p53 interaction-inverted by mutant p53-forms a critical regulatory node. Throughout, the direction and magnitude of cross-talk prove highly dependent on cell type, ligand identity and kinetics, and species-distinctions often underappreciated in the literature. Clarifying these context-specific determinants is essential for translating AHR-VDR cross-regulation into rational therapies in autoimmunity, mucosal inflammation, dermatology, and oncology. - Source: PubMed
Publication date: 2026/09/08
Alqahtani Mohammed A - Di(2-ethylhexyl) phthalate (DEHP) and diisononyl phthalate (DiNP) are plasticizers used in many consumer products. Both phthalates alter estrous cyclicity, fertility indices, and folliculogenesis throughout the reproductive lifespan. Our companion paper showed that exposure to a phthalate mixture containing DEHP and DiNP altered the aryl hydrocarbon receptor (AHR) signaling pathway in the ovary. However, limited information was available on how DEHP and DiNP individually affect the AHR signaling pathway in the ovary throughout reproductive aging. Thus, we hypothesized that DEHP and DiNP individually affect the gene and protein expression and localization associated with the AHR pathway throughout the reproductive lifespan. We treated adult female CD-1 mice with corn oil control or doses (0.15 ppm, 1.5 ppm, or 1500 ppm) of DEHP and DiNP in the diet for 1-12 months. Sera were used to measure circulating estradiol (E2) concentrations. The AHR pathway was assessed using quantitative PCR (qPCR) for gene expression, RNAscopeTM in situ hybridization for transcript localization, and immunohistochemistry for protein localization. Exposure to DEHP, but not DiNP, reduced serum E2 after 1 month compared to control. DEHP exposure increased Cyp1a1 expression and CYP1B1 localization in the ovary after 6 months compared to control. DiNP also increased Arnt expression and CYP1B1 localization in the ovary after 1 month compared to control. DiNP exposure decreased Ahr and Cyp1a1 expression as well as CYP1A1 localization in the antral follicle after 12 months compared to control. Overall, DEHP and DiNP both influence the ovarian AHR pathway, but at different time points and doses. - Source: PubMed
Publication date: 2026/09/25
Dean Angela ESantacruz-Márquez RamsésSafar Adira MLaws Mary JSeaton Taylor AMiller EstellaHuff JustinHall Lydia MFlaws Jodi A - Phthalates are plasticizers and solvents used in numerous consumer products. Exposure to a phthalate mixture (Mix) alters estrous cyclicity, fertility indices, ovarian follicle dynamics, and steroidogenesis. In cultured antral follicles, phthalates alter the aryl hydrocarbon receptor (AHR) pathway, which is known for estradiol (E2) and xenobiotic metabolism. However, how phthalates affect the AHR pathway in the ovary in vivo and how this pathway changes throughout the reproductive lifespan are unknown. Thus, we hypothesized that expression and localization of genes and proteins in the AHR pathway change throughout the reproductive lifespan and in response to Mix exposure. We exposed adult female CD-1 mice to corn oil control or varying doses (0.15 ppm, 1.5 ppm, or 1500 ppm) of Mix for 1-12 months. Sera and ovaries were collected at each time point. Sera were used to determine circulating E2 concentrations. The AHR pathway in the ovaries was examined using quantitative PCR (qPCR) for gene expression, RNAscopeTM in situ hybridization for transcript localization, and immunohistochemistry for protein localization. The AHR pathway was altered throughout the reproductive lifespan, with increased Cyp1a1 expression and decreased CYP1B1 localization in the ovary at 13 months of age. Circulating E2 decreased throughout aging. Mix exposure altered Arnt and Ahr expression after 1 and 12 months, respectively. Additionally, Mix exposure increased CYP1A1 localization after 6 months, with areas of increased staining intensity in the ovary. Overall, the AHR pathway was altered with reproductive aging, and Mix exposure affected the pathway over time. - Source: PubMed
Publication date: 2026/09/25
Dean Angela ESantacruz-Márquez RamsésSafar Adira MLaws Mary JSeaton Taylor AMiller EstellaHuff JustinHall Lydia MFlaws Jodi A - Brain and muscle ARNT‑like 1 (BMAL1) is a core transcription factor of the molecular circadian clock and links daily timing with cardiovascular electrophysiology, metabolism, vascular function and inflammation. Altered BMAL1 expression or rhythmicity has been reported in arrhythmias, atherosclerosis, myocardial ischemia/reperfusion injury and heart failure. However, its specific role has remained elusive, as local effects in cardiovascular cells are often mixed with the broader effects of whole‑body circadian disruption. The present review addressed this gap by separating evidence from central and peripheral clocks, cell‑specific and systemic models, and experimental and human studies. Cardiomyocyte‑specific models provide relatively direct evidence that the local clock supports electrical stability, substrate use, mitochondrial homeostasis and contractile function. However, in endothelial cells, vascular smooth muscle cells and immune cells, the effects of BMAL1 are more variable and depend on cell type, metabolic conditions, disease stage and circadian phase. Human evidence remains mainly associative, whereas most mechanistic findings come from cell and animal studies. The present review also assessed small‑molecule clock modulators, chronotherapy and non‑pharmacological interventions, as well as time‑resolved multi‑omics and machine‑learning approaches. Current evidence does not support viewing BMAL1 as simply protective or harmful. A selective BMAL1‑binding small molecule has recently been identified, but its cardiovascular efficacy and safety have not been established. In addition, the clinical benefits of chronotherapy vary across treatments and patients. Further translation will require tissue‑specific human models, repeated sampling across biological time and prospective studies of treatment guided by individual circadian phases. - Source: PubMed
Publication date: 2026/09/25
Liang YuChen TingjinWen XuemeiLiu DanZhang ZhongjianLi WeiqingZhang Hengdi - Insulin clearance is a key determinant of circulating insulin availability, but its diurnal variation and relationship with circadian metabolic programs in metabolic dysfunction associated steatotic liver disease (MASLD) remain unclear. This study aimed to explore diurnal insulin clearance in humans and examine associated metabolic gene signatures in MASLD. - Source: PubMed
Publication date: 2026/08/29
Guo LinYin YiminSun YanyanZhou HongwenGong Yingyun