NADPH oxidase 4 deficiency reduces aquaporin-2 mRNA expression in cultured renal collecting duct principal cells via increased PDE3 and PDE4 activity.

The final control of renal water reabsorption occurs in the collecting duct (CD) and relies on regulated expression of aquaporin-2 (AQP2) in principal CD cells. AQP2 transcription is primarily induced by type 2 vasopressin receptor (V2R)-cAMP-protein kinase A (PKA) signaling but also by other factors, including TonEBP and NF-κB. NAPDH oxidase 4 (NOX4) represents a major source of reactive oxygen species (ROS) in the kidney.

Regulatory assessment of in vitro skin corrosion and irritation data within the European framework: Workshop recommendations.

Validated in vitro methods for skin corrosion and irritation were adopted by the OECD and by the European Union during the last decade. In the EU, Switzerland and countries adopting the EU legislation, these assays may allow the full replacement of animal testing for identifying and classifying compounds as skin corrosives, skin irritants, and non irritants. In order to develop harmonised recommendations on the use of in vitro data for regulatory assessment purposes within the European framework, a workshop was organized by the Swiss Federal Office of Public Health together with ECVAM and the BfR.

Gap junction protein Cx37 interacts with endothelial nitric oxide synthase in endothelial cells.

Objective: The gap junction protein connexin37 (Cx37) plays an important role in cell-cell communication in the vasculature. A C1019T Cx37 gene polymorphism, encoding a P319S substitution in the regulatory C terminus of Cx37 (Cx37CT), correlates with arterial stenosis and myocardial infarction in humans. This study was designed to identify potential binding partners for Cx37CT and to determine whether the polymorphism modified this interaction.

Molecular role of Cx37 in advanced atherosclerosis: a micro-array study.

Recently, we showed that connexin37 (Cx37) protects against early atherosclerotic lesion development by regulating monocyte adhesion. The expression of this gap junction protein is altered in mouse and human atherosclerotic lesions; it is increased in macrophages newly recruited to the lesions and disappears from the endothelium of advanced plaques. To obtain more insight into the molecular role of Cx37 in advanced atherosclerosis, we used micro-array analysis for gene expression profiling in aortas of ApoE(-/-) and Cx37(-/-)ApoE(-/-) mice before and after 18 weeks of cholesterol-rich diet.

Functional differences between human Cx37 polymorphic hemichannels.

A polymorphism in the human Cx37 gene (C1019T), resulting in a non-conservative amino acid change in the regulatory C-terminus of the Cx37 protein (P319S), has been proposed as a prognostic marker for atherosclerosis. We have recently demonstrated that Cx37 hemichannels control the initiation of atherosclerotic plaque development by regulating ATP-dependent monocyte adhesion in atherosclerosis-susceptible apolipoprotein E-deficient mice. In this study, we have measured the electrical properties of Cx37 hemichannels (HCs) and gap junction channels (GJCs) with voltage-clamp methods.

Targeting connexin 43 prevents platelet-derived growth factor-BB-induced phenotypic change in porcine coronary artery smooth muscle cells.

We previously reported that reducing the expression of the gap junction protein connexin (Cx)43 in mice restricts intimal thickening formation after acute vascular injury by limiting the inflammatory response and the proliferation and migration of smooth muscle cells (SMCs) toward the damaged site. SMC populations isolated from porcine coronary artery exhibit distinct phenotypes: spindle-shaped (S) and rhomboid (R). S-SMCs are predominant in the normal media, whereas R-SMCs are recovered in higher proportion from stent-induced intimal thickening, suggesting that they participate in the restenotic process.

Connexin37 protects against atherosclerosis by regulating monocyte adhesion.

A genetic polymorphism in the human gene encoding connexin37 (CX37, encoded by GJA4, also known as CX37) has been reported as a potential prognostic marker for atherosclerosis. The expression of this gap-junction protein is altered in mouse and human atherosclerotic lesions: it disappears from the endothelium of advanced plaques but is detected in macrophages recruited to the lesions. The role of CX37 in atherogenesis, however, remains unknown.

Connexins in atherosclerosis.

Remodeling of the vascular wall plays a central role in many physiological processes, but also in the pathogenesis of cardiovascular diseases such as atherosclerosis and restenosis. Atherosclerosis represents the major cause of death and disability in adult populations of Western societies. Angioplasty is a common and effective method of treatment for coronary atherosclerosis, but restenosis after the procedure continues to be a serious clinical complication.

Gap junctional communication in tissue inflammation and repair.

Local injury induces a complex orchestrated response to stimulate healing of injured tissues, cellular regeneration and phagocytosis. Practically, inflammation is defined as a defense process whereby fluid and white blood cells accumulate at a site of injury. The balance of cytokines, chemokines, and growth factors is likely to play a key role in regulating important cell functions such as migration, proliferation, and matrix synthesis during the process of inflammation.