TY - JOUR
T1 - A comprehensive data mining study shows that most nuclear receptors act as newly proposed homeostasis-associated molecular pattern receptors
AU - Wang, Luqiao
AU - Nanayakkara, Gayani
AU - Yang, Qian
AU - Tan, Hongmei
AU - Drummer, Charles
AU - Sun, Yu
AU - Shao, Ying
AU - Fu, Hangfei
AU - Cueto, Ramon
AU - Shan, Huimin
AU - Bottiglieri, Teodoro
AU - Li, Ya Feng
AU - Johnson, Candice
AU - Yang, William Y.
AU - Yang, Fan
AU - Xu, Yanjie
AU - Xi, Hang
AU - Liu, Weiqing
AU - Yu, Jun
AU - Choi, Eric T.
AU - Cheng, Xiaoshu
AU - Wang, Hong
AU - Yang, Xiaofeng
N1 - Publisher Copyright:
© The Author(s).
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - Atherosclerosis
KW - Cardiovascular disease
KW - Homeostasis-associated molecular pattern receptors
KW - Metabolic disease
KW - Nuclear receptors (NRs)
UR - http://www.scopus.com/inward/record.url?scp=85042307464&partnerID=8YFLogxK
U2 - 10.1186/S13045-017-0526-8
DO - 10.1186/S13045-017-0526-8
M3 - Article
C2 - 29065888
AN - SCOPUS:85042307464
SN - 1756-8722
VL - 10
JO - Journal of Hematology and Oncology
JF - Journal of Hematology and Oncology
M1 - 168
ER -