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A comprehensive data mining study shows that most nuclear receptors act as newly proposed homeostasis-associated molecular pattern receptors
- Source :
- Journal of Hematology & Oncology, Vol 10, Iss 1, Pp 1-41 (2017), Journal of Hematology & Oncology
- Publication Year :
- 2017
- Publisher :
- BMC, 2017.
-
Abstract
- Background Nuclear receptors (NRs) can regulate gene expression; therefore, they are classified as transcription factors. Despite the extensive research carried out on NRs, still several issues including (1) the expression profile of NRs in human tissues, (2) how the NR expression is modulated during atherosclerosis and metabolic diseases, and (3) the overview of the role of NRs in inflammatory conditions are not fully understood. Methods To determine whether and how the expression of NRs are regulated in physiological/pathological conditions, we took an experimental database analysis to determine expression of all 48 known NRs in 21 human and 17 murine tissues as well as in pathological conditions. Results We made the following significant findings: (1) NRs are differentially expressed in tissues, which may be under regulation by oxygen sensors, angiogenesis pathway, stem cell master regulators, inflammasomes, and tissue hypo-/hypermethylation indexes; (2) NR sequence mutations are associated with increased risks for development of cancers and metabolic, cardiovascular, and autoimmune diseases; (3) NRs have less tendency to be upregulated than downregulated in cancers, and autoimmune and metabolic diseases, which may be regulated by inflammation pathways and mitochondrial energy enzymes; and (4) the innate immune sensor inflammasome/caspase-1 pathway regulates the expression of most NRs. Conclusions Based on our findings, we propose a new paradigm that most nuclear receptors are anti-inflammatory homeostasis-associated molecular pattern receptors (HAMPRs). Our results have provided a novel insight on NRs as therapeutic targets in metabolic diseases, inflammations, and malignancies. Electronic supplementary material The online version of this article (10.1186/s13045-017-0526-8) contains supplementary material, which is available to authorized users.
- Subjects :
- 0301 basic medicine
Cancer Research
Receptors, Cytoplasmic and Nuclear
Angiogenesis Pathway
Metabolic disease
Biology
lcsh:RC254-282
03 medical and health sciences
Downregulation and upregulation
Gene expression
medicine
Data Mining
Homeostasis
Humans
Nuclear receptors (NRs)
Receptor
Molecular Biology
Transcription factor
Innate immune system
lcsh:RC633-647.5
Research
Homeostasis-associated molecular pattern receptors
Inflammasome
Hematology
lcsh:Diseases of the blood and blood-forming organs
Atherosclerosis
Cardiovascular disease
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
humanities
Cell biology
030104 developmental biology
Oncology
Nuclear receptor
Immunology
human activities
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 17568722
- Volume :
- 10
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of Hematology & Oncology
- Accession number :
- edsair.doi.dedup.....ce4ebace26b8d9dfc422767b4dec22b2