A comprehensive data mining study shows that most nuclear receptors act as newly proposed homeostasis-associated molecular pattern receptors

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

doi:10.1186/s13045-017-0526-8

Table 13 Nuclear receptors are more downregulated than upregulated in human diseases

From: A comprehensive data mining study shows that most nuclear receptors act as newly proposed homeostasis-associated molecular pattern receptors

Disease	Tissue/cell type	Number		Upregulated gene		Downregulated gene		PMID/GEO ID
Disease	Tissue/cell type	Up	Down
A. Nuclear receptors have the tendency to be downregulated than being upregulated in rheumatoid arthritis
					Fold*		Fold*
					∆		∆
Rheumatoid arthritis	Synovial tissue	3	9	NR1H3	2.08	NR1A1	−20	24690414/GSE55235
				NR1I1	2.12	NR1C3	−2.56
				NR3A1	2.59	NR1D1	−20
						NR2F1	−2.94
						NR3C3	−2
						NR3C4	−2.22
						NR4A1	−4.76
						NR4A2	−10
						NR4A3	−3.85
B. Nuclear receptors are more downregulated than upregulated in metabolic diseases in humans
					Fold**		Fold**
					∆		∆
Family hypercholesterolemia	T cells	7	11	NR1B3	1.41	NR1A1	−1.3	–/GSE6088
				NR1C3	1.94	NR1B1	−1.22
				NR1I1	1.75	NR1B2	−1.72
				NR3C4	1.97	NR1C1	−1.72
				NR4A2	2.03	NR1F1	−2
				NR4A3	1.5	NR1F2	−1.79
				NR0B1	2.36	NR1H3	−1.28
						NR3B3	−2.08
						NR3C1	−1.22
Family hypercholesterolemia	Monocytes	10	12	NR1B1	1.23	NR1A1	−2.27	19040724/GSE6054
				NR1F3	2.38	NR1B2	−1.72
				NR1I1	1.31	NR1C1	−1.59
				NR2F6	2.61	NR1F1	−1.52
				NR3B2	1.33	NR1H3	−1.28
				NR4A1	1.94	NR2A2	−2.13
				NR4A2	2.06	NR2C1	−1.47
				NR5A1	2.1	NR2C2	−1.19
				NR6A1	1.62	NR2E3	−2.63
				NR0B1	2.02	NR3A1	−2
						NR3A2	−1.79
						NR3C1	−1.28
Metabolic syndrome	Peripheral blood	0	1			NR4A3	−1.54	21368773/GSE23561
Type 2 diabetes	Arterial tissue	0	2			NR1B2	−1.28	22340758/GSE13760
Type 2 diabetes	Arterial tissue	0	2			NR3C3	−1.12	22340758/GSE13760
Type 1 diabetes	Peripheral blood mononuclear cell	1	2	NR3C4	1.2	NR1F1	−1.89	–/GSE55100
Type 1 diabetes	Peripheral blood mononuclear cell	1	2			NR4A3	−1.2	–/GSE55100
Morbidly obese	Adipose stem cells	3	3	NR4A1	8.06	NR1A1	−1.2	24040759/GSE48964
				NR4A2	12.64	NR1D1	−1.2
				NR4A3	4.44	NR2C2	−1.25
Morbidly obese	Human omental adipose tissue	1	1	NR4A2	3.5	NR2B3	−2.44	20678967/GSE15773
Homocysteine (100 μM)	Human aortic smooth muscle cells	3	3	NR2B3	1.2	NR1H3	−1.33	18602108/GSE9490
				NR3A2	1.61	NR2F2	−1.7
				NR4A3	1.49	NR4A2	−1.24
Hypertension	Carotid artery atheromatous plaques	0	2			NR1A2	−2.04	23660665/GSE43292
Hypertension	Carotid artery atheromatous plaques	0	2			NR3C3	−2	23660665/GSE43292
C. Nuclear receptors are significantly downregulated than upregulated in human aortic endothelial cells (HAECs) treated with oxidized low-density lipoproteins (Ox-LDLs) in a time-dependent manner
					Fold*		Fold*
					∆		∆
Treated with Ox-LDL for 6 h	HAEC	4	3	NR1I2	2.18	NR1B2	−3.57	19279231/GSE13139
				NR2A2	3.8	NR1F1	−5.26
				NR3A2	3.04	NR4A1	−2.56
				NR5A2	4
Treated with Ox-LDL for 12 h		0	7			NR1B1	−2.86
						NR1B2	−5.56
						NR1F1	−2.86
						NR1H4	−5.88
						NR2A2	−2.04
						NR3A1	−2.94
						NR3C3	−2.33
Treated with Ox-LDL for 24 h		5	7	NR1C1	2.24	NR1B1	−2.56
				NR1I1	2.01	NR1B2	−2.17
				NR3A2	5.09	NR1B3	−2.04
				NR3B2	2.34	NR1H4	−4.55
				NR5A2	5.81	NR1I2	−2.5
						NR2A2	−2.13
						NR2F6	−4.55

Abbreviations: HAECs human aortic endothelial cells, Ox-LDL oxidized low-density lipoprotein
*Fold change > 2
**Fold change > 1.2

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