Retinoic acid receptor alpha

evidence_locator

Abstract

experimental_model

Normal human tracheobronchial epithelial cultures with receptor-selective agonists/antagonists.

exposure

Receptor-selective agonists/antagonists

limitations

Transcript changes do not establish improved mucus clearance.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Homo sapiens

plain_language

RAR signaling helps cultured airway cells adopt a mucus-producing program.

primary_references

[va-koo-1999] Role of retinoid receptors in the regulation of mucin gene expression by retinoic acid in human tracheobronchial epithelial cells (1999). https://pubmed.ncbi.nlm.nih.gov/10024510/ DOI: 10.1042/bj3380351

tissue_or_cell_type

Normal tracheobronchial epithelial cells

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1357–1368

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Normal human tracheobronchial epithelial cultures with receptor-selective agonists/antagonists. · source_derived_draft · unverified_draft

### va-sig-rara-airway-mucin RAR alpha-selective pharmacology supported RAR alpha-mediated induction of airway mucin transcripts, including MUC5AC. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: RAR signaling helps cultured airway cells adopt a mucus-producing program. organism: Homo sapiens tissue_or_cell_type: Normal tracheobronchial epithelial cells experimental_model: Normal human tracheobronchial epithelial cultures with receptor-selective agonists/antagonists. limitations: Transcript changes do not establish improved mucus clearance. evidence_locator: Abstract exposure: Receptor-selective agonists/antagonists [va-koo-1999] Role of retinoid receptors in the regulation of mucin gene expression by retinoic acid in human tracheobronchial epithelial cells (1999). https://pubmed.ncbi.nlm.nih.gov/10024510/ DOI: 10.1042/bj3380351

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_locator

Discussion and T-cell activation experiments

experimental_model

Vitamin A-insufficient and Rara-deficient mice; stimulated CD4 T cells.

exposure

Rara loss or RAR antagonism

limitations

Does not negate RA effects on Treg differentiation.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Mus musculus

plain_language

Loss of receptor signaling can weaken effector-cell expansion.

primary_references

[va-hall-2011] Essential role for retinoic acid in the promotion of CD4(+) T cell effector responses via retinoic acid receptor alpha (2011). https://pmc.ncbi.nlm.nih.gov/articles/PMC3415227/ DOI: 10.1016/j.immuni.2011.03.003

tissue_or_cell_type

CD4 T cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1279–1290

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Vitamin A-insufficient and Rara-deficient mice; stimulated CD4 T cells. · source_derived_draft · unverified_draft

### va-sig-rara-t-cell-proliferation Rara-deficient or RAR-antagonized T cells proliferated less efficiently after stimulation. Condition category: machinery_impairment nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Loss of receptor signaling can weaken effector-cell expansion. organism: Mus musculus tissue_or_cell_type: CD4 T cells experimental_model: Vitamin A-insufficient and Rara-deficient mice; stimulated CD4 T cells. limitations: Does not negate RA effects on Treg differentiation. evidence_locator: Discussion and T-cell activation experiments exposure: Rara loss or RAR antagonism [va-hall-2011] Essential role for retinoic acid in the promotion of CD4(+) T cell effector responses via retinoic acid receptor alpha (2011). https://pmc.ncbi.nlm.nih.gov/articles/PMC3415227/ DOI: 10.1016/j.immuni.2011.03.003

evidence_locator

Abstract

experimental_model

Human TIF2 cloning; in vitro receptor-domain interactions and cellular reporters.

exposure

Agonist versus control; AF-2 mutants

limitations

Domain assays do not resolve every endogenous chromatin complex.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Human TIF2 and engineered receptor domains

plain_language

An activated receptor gains a binding surface for a transcriptional coactivator.

primary_references

[va-voegel-1996] TIF2, a 160 kDa transcriptional mediator for the ligand-dependent activation function AF-2 of nuclear receptors (1996). https://pubmed.ncbi.nlm.nih.gov/8670870/ DOI: 10.1002/j.1460-2075.1996.tb00736.x

tissue_or_cell_type

Cell-free and cellular interaction assays

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1162–1173

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human TIF2 cloning; in vitro receptor-domain interactions and cellular reporters. · source_derived_draft · unverified_draft

### va-sig-rara-tif2-recruitment The agonist-bound RAR ligand-binding domain interacted with TIF2 in an AF-2-dependent manner. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: An activated receptor gains a binding surface for a transcriptional coactivator. organism: Human TIF2 and engineered receptor domains tissue_or_cell_type: Cell-free and cellular interaction assays experimental_model: Human TIF2 cloning; in vitro receptor-domain interactions and cellular reporters. limitations: Domain assays do not resolve every endogenous chromatin complex. evidence_locator: Abstract exposure: Agonist versus control; AF-2 mutants [va-voegel-1996] TIF2, a 160 kDa transcriptional mediator for the ligand-dependent activation function AF-2 of nuclear receptors (1996). https://pubmed.ncbi.nlm.nih.gov/8670870/ DOI: 10.1002/j.1460-2075.1996.tb00736.x

evidence_locator

Figure 2

experimental_model

Recombinant receptors, gel shifts, coimmunoprecipitation and CV-1 reporters.

exposure

Receptor coexpression/reconstitution

limitations

Synthetic response elements; not every genomic site.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Recombinant receptors

plain_language

Two distinct receptor proteins assemble a DNA-binding complex.

primary_references

[va-kliewer-1992] Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling (1992). https://pubmed.ncbi.nlm.nih.gov/1310351/ DOI: 10.1038/355446a0

tissue_or_cell_type

Cell-free DNA-binding assay

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1082–1093

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant receptors, gel shifts, coimmunoprecipitation and CV-1 reporters. · source_derived_draft · unverified_draft

### va-sig-rara-rxra-cooperative-binding RXRA associated with RARA and cooperatively bound retinoid response DNA. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Two distinct receptor proteins assemble a DNA-binding complex. organism: Recombinant receptors tissue_or_cell_type: Cell-free DNA-binding assay experimental_model: Recombinant receptors, gel shifts, coimmunoprecipitation and CV-1 reporters. limitations: Synthetic response elements; not every genomic site. evidence_locator: Figure 2 exposure: Receptor coexpression/reconstitution [va-kliewer-1992] Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling (1992). https://pubmed.ncbi.nlm.nih.gov/1310351/ DOI: 10.1038/355446a0

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

false

experimental_model

Ovarian graft and breeding experiment

exposure

E17.5 mutant ovaries grafted into nude females; mating with wild-type males.

limitations

Recipient support bypassed mutant fetal lethality; not intact-knockout fertility.

nutrient_topic

Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Mus musculus

plain_language

The receptor-deficient ovarian grafts could produce functional eggs.

primary_references

[vernet2020] Meiosis occurs normally in the fetal ovary of mice lacking all retinoic acid receptors. (2020). https://pubmed.ncbi.nlm.nih.gov/32917583/ DOI: 10.1126/sciadv.aaz1139

tissue_or_cell_type

fetal ovarian graft in adult recipient

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin A expansion: reproduction, light-driven vision and shared mechanisms (2026-09-17) · lines 317–328

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ovarian graft and breeding experiment · source_derived_draft · unverified_draft

### va-repro-rar-null-functional-oocytes RAR-null fetal ovaries grafted into adult females produced oocytes that contributed to offspring carrying the deleted alleles. Condition category: machinery_impairment nutrient_topic: Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. plain_language: The receptor-deficient ovarian grafts could produce functional eggs. organism: Mus musculus tissue_or_cell_type: fetal ovarian graft in adult recipient experimental_model: Ovarian graft and breeding experiment limitations: Recipient support bypassed mutant fetal lethality; not intact-knockout fertility. exposure: E17.5 mutant ovaries grafted into nude females; mating with wild-type males. cross_nutrient: false [vernet2020] Meiosis occurs normally in the fetal ovary of mice lacking all retinoic acid receptors. (2020). https://pubmed.ncbi.nlm.nih.gov/32917583/ DOI: 10.1126/sciadv.aaz1139

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

false

experimental_model

Timed receptor deletion with excision reporter

exposure

Tamoxifen induction at E9.5; meiosis assessed at E15.5.

limitations

Does not test dietary vitamin A deprivation or every possible RAR-independent action.

nutrient_topic

Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Mus musculus

plain_language

The tested fetal ovarian program progressed without the RA receptors.

primary_references

[vernet2020] Meiosis occurs normally in the fetal ovary of mice lacking all retinoic acid receptors. (2020). https://pubmed.ncbi.nlm.nih.gov/32917583/ DOI: 10.1126/sciadv.aaz1139

tissue_or_cell_type

fetal ovary

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin A expansion: reproduction, light-driven vision and shared mechanisms (2026-09-17) · lines 304–315

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Timed receptor deletion with excision reporter · source_derived_draft · unverified_draft

### va-repro-rar-null-ovarian-meiosis Fetal ovarian germ cells lacking all RARs expressed meiotic markers and reached zygotene, challenging an obligatory RAR trigger. Condition category: machinery_impairment nutrient_topic: Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. plain_language: The tested fetal ovarian program progressed without the RA receptors. organism: Mus musculus tissue_or_cell_type: fetal ovary experimental_model: Timed receptor deletion with excision reporter limitations: Does not test dietary vitamin A deprivation or every possible RAR-independent action. exposure: Tamoxifen induction at E9.5; meiosis assessed at E15.5. cross_nutrient: false [vernet2020] Meiosis occurs normally in the fetal ovary of mice lacking all retinoic acid receptors. (2020). https://pubmed.ncbi.nlm.nih.gov/32917583/ DOI: 10.1126/sciadv.aaz1139

duration

Culture treatment

experimental_model

Myeloid leukaemia cell lines and primary human AML models

exposure

All-trans retinoic acid

limitations

A transcript rise is not a measured rise in enzyme activity, and pharmacological ATRA is not dietary vitamin A.

organism

Homo sapiens

plain_language

Retinoic acid made leukaemia cells produce more of the TET2 enzyme.

primary_references

[celrep-2025] Retinoic acid and ascorbate synergize to suppress myeloid leukemia via TET2 activation (2025). https://pubmed.ncbi.nlm.nih.gov/41037397/ DOI: 10.1016/j.celrep.2025.116379

tissue

Myeloid leukaemia cells

TET2 loss and malignancy: the step between a nutrient-responsive enzyme and the disease (2026-09-23) · lines 143–151

Original AI-assisted curation of twelve primary studies located by Europe PMC title search, with every statement drafted from the retrieved abstract. Two pairs share a laboratory and are recorded as one line of evidence each. Genetic loss of function, pharmacological exposure and dietary depletion are kept as separate record types. Not publisher full text. · supports · Myeloid leukaemia cell lines and primary human AML models · source_derived_draft · unverified_draft

## atra-induces-tet2-transcription All-trans retinoic acid induced retinoic-acid-receptor-alpha-mediated TET2 transcription in myeloid leukaemia cells. Model/species: Myeloid leukaemia cell lines and primary human AML models Organism: Homo sapiens Tissue/system: Myeloid leukaemia cells Exposure: All-trans retinoic acid Duration: Culture treatment Limits: A transcript rise is not a measured rise in enzyme activity, and pharmacological ATRA is not dietary vitamin A. Primary reference: [celrep-2025] Retinoic acid and ascorbate synergize to suppress myeloid leukemia via TET2 activation (2025). https://pubmed.ncbi.nlm.nih.gov/41037397/ DOI: 10.1016/j.celrep.2025.116379

cross_nutrient

Retinoid signaling -> calcium-store remodeling.

experimental_model

Neonatal mouse bone organ culture.

limitations

Receptor pharmacology is not proof of a human dietary effect.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Mus musculus

plain_language

A vitamin A metabolite increased a signal that promotes bone resorption.

primary_references

[va-conaway2011] Retinoids stimulate periosteal bone resorption by enhancing the protein RANKL, a response inhibited by monomeric glucocorticoid receptor (2011). https://pubmed.ncbi.nlm.nih.gov/21715325/ DOI: 10.1074/jbc.m111.247734

tissue_or_cell_type

Calvarial bone

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1614–1624

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Neonatal mouse bone organ culture. · source_derived_draft · unverified_draft

### va-rar-alpha-rankl-bone Retinoic acid increased RANKL and the RANKL/OPG ratio in mouse calvarial cultures; receptor-selective results implicated RARalpha. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: A vitamin A metabolite increased a signal that promotes bone resorption. organism: Mus musculus tissue_or_cell_type: Calvarial bone experimental_model: Neonatal mouse bone organ culture. limitations: Receptor pharmacology is not proof of a human dietary effect. cross_nutrient: Retinoid signaling -> calcium-store remodeling. [va-conaway2011] Retinoids stimulate periosteal bone resorption by enhancing the protein RANKL, a response inhibited by monomeric glucocorticoid receptor (2011). https://pubmed.ncbi.nlm.nih.gov/21715325/ DOI: 10.1074/jbc.m111.247734

evidence_locator

Abstract

experimental_model

Transfected COS-1 nucleosol; ligand competition and chimeric receptor reporters.

exposure

Isomer competition

limitations

Does not establish endogenous tissue concentrations.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Recombinant receptors in COS-1 cells

plain_language

An RXR-binding retinoid can also activate RAR pathways.

primary_references

[va-allenby-1993] Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids (1993). https://pubmed.ncbi.nlm.nih.gov/8380496/ DOI: 10.1073/pnas.90.1.30

tissue_or_cell_type

Nuclear extracts

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1043–1054

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transfected COS-1 nucleosol; ligand competition and chimeric receptor reporters. · source_derived_draft · unverified_draft

### va-sig-9cis-rar-binding 9-cis RA also bound RAR alpha, beta and gamma; it was not RXR-selective. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: An RXR-binding retinoid can also activate RAR pathways. organism: Recombinant receptors in COS-1 cells tissue_or_cell_type: Nuclear extracts experimental_model: Transfected COS-1 nucleosol; ligand competition and chimeric receptor reporters. limitations: Does not establish endogenous tissue concentrations. evidence_locator: Abstract exposure: Isomer competition [va-allenby-1993] Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids (1993). https://pubmed.ncbi.nlm.nih.gov/8380496/ DOI: 10.1073/pnas.90.1.30

evidence_locator

Abstract

experimental_model

Transfected COS-1 nucleosol; ligand competition and chimeric receptor reporters.

exposure

Radioligand competition

limitations

Binding affinity is not a dietary threshold.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Recombinant receptors in African green monkey COS-1 cells

plain_language

The all-trans isomer directly engages RAR proteins.

primary_references

[va-allenby-1993] Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids (1993). https://pubmed.ncbi.nlm.nih.gov/8380496/ DOI: 10.1073/pnas.90.1.30

tissue_or_cell_type

Nuclear extracts

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1030–1041

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transfected COS-1 nucleosol; ligand competition and chimeric receptor reporters. · source_derived_draft · unverified_draft

### va-sig-atra-rar-binding All-trans RA bound the tested RAR alpha, beta and gamma preparations with high affinity. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: The all-trans isomer directly engages RAR proteins. organism: Recombinant receptors in African green monkey COS-1 cells tissue_or_cell_type: Nuclear extracts experimental_model: Transfected COS-1 nucleosol; ligand competition and chimeric receptor reporters. limitations: Binding affinity is not a dietary threshold. evidence_locator: Abstract exposure: Radioligand competition [va-allenby-1993] Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids (1993). https://pubmed.ncbi.nlm.nih.gov/8380496/ DOI: 10.1073/pnas.90.1.30

evidence_locator

Abstract

experimental_model

Receptor interaction, DNA binding and transfection experiments.

exposure

Receptor cotransfection and RA

limitations

Reporter-system dependence; no nutrient dose response.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Engineered cellular receptor system

plain_language

RXRA can assist RAR signaling without equivalent activation of both partners.

primary_references

[va-zhang-1992] Retinoid X receptor is an auxiliary protein for thyroid hormone and retinoic acid receptors (1992). https://pubmed.ncbi.nlm.nih.gov/1310350/ DOI: 10.1038/355441a0

tissue_or_cell_type

Transfection reporters

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1123–1134

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Receptor interaction, DNA binding and transfection experiments. · source_derived_draft · unverified_draft

### va-sig-rxra-rar-transactivation RXRA enhanced RAR-mediated transcription at RA concentrations insufficient to substantially activate RXRA itself. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: RXRA can assist RAR signaling without equivalent activation of both partners. organism: Engineered cellular receptor system tissue_or_cell_type: Transfection reporters experimental_model: Receptor interaction, DNA binding and transfection experiments. limitations: Reporter-system dependence; no nutrient dose response. evidence_locator: Abstract exposure: Receptor cotransfection and RA [va-zhang-1992] Retinoid X receptor is an auxiliary protein for thyroid hormone and retinoic acid receptors (1992). https://pubmed.ncbi.nlm.nih.gov/1310350/ DOI: 10.1038/355441a0