Table 2.

CITED2 involvement in disease states.

Disease states	CITED2 relevance	References
Glucose homeostasis and diabetes	Required for the regulation of hepatic gluconeogenesis	[50,156]
	Downregulation mediates high glucose-induced endoplasmic reticulum stress-dependent apoptosis	[51]
	Upregulated in vascular tissue of patients with obesity and type 2 diabetes	[157]
	Impairs insulin signaling in endothelial cells	[158]
	Decreased in heart tissue of maternal diabetic-exposed embryos	[58]
	Increased expression in adipose-derived stem cells from diabetic patients, which exhibit decreased proliferation and wound healing abilities	[159]
Inflammation	Potent repressor of macrophage proinflammatory activation	[23]
	Myeloid deficiency significantly increases macrophage and neutrophil recruitment	[32]
	Restrains signal transducer and activator of transcription 1 (STAT1) and interferon regulatory factor 1 (IRF1) signaling in macrophages and limits development of atherosclerotic plaques	[73]
	Deficiency results in enhanced placenta interferon-responsive gene expression	[44]
Pregnancy related disorders	Lower levels in cumulus cells are associated with higher rates of oocyte fertilization and embryo implantation	[161]
	Dysregulated in the placenta from mothers with hypertension	[160]
	Upregulated in placentas from women with severe preeclampsia	[61]
	Upregulated in placentas from growth restricted fetuses	[87]
	Decreased expression in endoplasmic-reticulum stress-induced BeWo choriocarcinoma cells (note: CITED2 may be restricted to the transformed character of the cells and not their trophoblast origin)	[62]
Cardiovascular disease	Essential for heart development	[20,21,26,27,44,162]
	Mutations contribute to congenital heart disease	[24,28-30,52-57]
Lung development	Dysregulation results in aberrations in lung development	[44,163,164]
Neurodevelopmental disorders	Deficiency results in an abnormal neural development (exencephaly) in the mouse, a phenotype reduced with folic acid treatment	[4,21,40]