VSMC-specific EP4 deletion exacerbates angiotensin II-induced aortic dissection by increasing vascular inflammation and blood pressure.

Prostaglandin E2 (PGE2) plays an important role in vascular homeostasis. Its receptor, E-prostanoid receptor 4 (EP4) is essential for physiological remodeling of the ductus arteriosus (DA). However, the role of EP4 in pathological vascular remodeling remains largely unknown.

Platelet-mediated adhesion facilitates leukocyte sequestration in hypoxia-reoxygenated microvessels.

Leukocyte transendothelial migration and sequestration are two distinct outcomes following leukocyte adhesion to endothelium during ischemia-reperfusion injury, in which platelets may play a pivotal role. In the present study, we established an in vitro hypoxia-reoxygenation model to mimic ischemia-reperfusion injury and found platelet pre-incubation significantly increased leukocyte adhesion to endothelial cells after hyoxia-reoxygenation (over 67%). Blockade of endothelial-cell-expressed adhesion molecules inhibited leukocyte direct adhesion to endothelial cells, while platelet-mediated leukocyte adhesion was suppressed by blockade of platelet-expressed adhesion molecules.

Disruption of prostaglandin E2 receptor EP4 impairs urinary concentration via decreasing aquaporin 2 in renal collecting ducts.

The antidiuretic hormone arginine vasopressin is a systemic effector in urinary concentration. However, increasing evidence suggests that other locally produced factors may also play an important role in the regulation of water reabsorption in renal collecting ducts. Recently, prostaglandin E2 (PGE2) receptor EP4 has emerged as a potential therapeutic target for the treatment of nephrogenic diabetes insipidus, but the underlying mechanism is unknown.

Farnesoid X receptor (FXR) gene deficiency impairs urine concentration in mice.

The farnesoid X receptor (FXR) is a ligand-activated transcription factor belonging to the nuclear receptor superfamily. FXR is mainly expressed in liver and small intestine, where it plays an important role in bile acid, lipid, and glucose metabolism. The kidney also has a high FXR expression level, with its physiological function unknown.

Metformin induces renal medullary interstitial cell apoptosis in type 2 diabetic mice.

Objective: Metformin is a first-line antidiabetic drug for type 2 diabetes (T2D) with a relatively good safety profile. Metformin activates AMP-activated protein kinase (AMPK), which is crucial in maintaining renal medullary function, with inappropriate AMPK activation facilitating renal medullary interstitial cells (RMICs) apoptosis under hypertonic challenge. The present study was to determine the effects of metformin on RMIC survival in both normal and T2D mice.

Targeted disruption of the prostaglandin E2 E-prostanoid 2 receptor exacerbates vascular neointimal formation in mice.

Objective: Restenosis after angioplasty remains a major clinical problem. Prostaglandin E(2) (PGE(2)) plays an important role in vascular homeostasis. The PGE(2) receptor E-prostanoid 2 (EP2) is involved in the proliferation and migration of various cell types.