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Wang L , Nanayakkara G , Yang Q , Tan H , Drummer C , Sun Y , Shao Y , Fu H , Cueto R , Shan H , Bottiglieri T , Li YF , Johnson C , Yang WY , Yang F , Xu Y , Xi H , Liu W , Yu J , Choi ET , Cheng X , Wang H , Yang X
A comprehensive data mining study shows that most nuclear receptors act as newly proposed homeostasis-associated molecular pattern receptors
J Hematol Oncol. 2017 Oct 24;10(1) :168
PMID: 29065888    PMCID: PMC5655880    URL: https://www.ncbi.nlm.nih.gov/pubmed/29065888
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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.
1756-8722 Wang, Luqiao Nanayakkara, Gayani Yang, Qian Tan, Hongmei Drummer, Charles Sun, Yu Shao, Ying Fu, Hangfei Cueto, Ramon Shan, Huimin Bottiglieri, Teodoro Li, Ya-Feng Johnson, Candice Yang, William Y Yang, Fan Xu, Yanjie Xi, Hang Liu, Weiqing Yu, Jun Choi, Eric T Cheng, Xiaoshu Wang, Hong Yang, Xiaofeng ORCID: http://orcid.org/0000-0002-6854-6195 R01 HL131460/HL/NHLBI NIH HHS/United States Journal Article England J Hematol Oncol. 2017 Oct 24;10(1):168. doi: 10.1186/s13045-017-0526-8.