The inositol Inpp5k 5-phosphatase affects osmoregulation through the vasopressin-aquaporin 2 pathway in the collecting system

Inositol Inpp5k (or Pps, SKIP) is a member of the inositol polyphosphate 5-phosphatases family with a poorly characterized function in vivo. In this study, we explored the function of this inositol 5-phosphatase in mice and cells overexpressing the 42-kDa mouse Inpp5k protein. Inpp5k transgenic mice present defects in water metabolism characterized by a reduced plasma osmolality at baseline, a delayed urinary water excretion following a water load, and an increased acute response to vasopressin. These defects are associated with the expression of the Inpp5k transgene in renal collecting ducts and with alterations in the arginine vasopressin/aquaporin-2 signalling pathway in this tubular segment. Analysis in a mouse collecting duct mCCD cell line revealed that Inpp5k overexpression leads to increased expression of the arginine vasopressin receptor type 2 and increased cAMP response to arginine vasopressin, providing a basis for increased aquaporin-2 expression and plasma membrane localization with increased osmotically induced water transport. Altogether, our results indicate that Inpp5k 5-phosphatase is important for the control of the arginine vasopressin/aquaporin-2 signalling pathway and water transport in kidney collecting duct

Prolifération et différenciation des cellules musculaires lisses aortiques (implication des messagers phospholipidiques nucléaires)

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Role of reactive oxygen species in atherosclerosis: Lessons from murine genetic models

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Elastin fragmentation and atherosclerosis progression: The elastokine concept

International audienceAtherosclerosis is a progressive multifaceted inflammatory disease affecting large-and medium-sized arteries. Typical feature of this disease is the formation and build-up of atherosclerotic plaques characterized by vascular extracellular matrix degradation and remodeling. Many studies have documented degradation of native elastin, the main extracellular matrix protein responsible for resilience and elasticity of arteries, by local release of elastases, leading to the production of elastin-derived peptides (EDP). These peptides have been proposed to actively participate in the progression of the disease by accelerating different biological processes, such as LDL oxidation and calcification of the vascular wall. These pathophysiological effects are mediated by the binding of EDP on a peculiar heterotrimeric receptor named elastin receptor complex (ERC). In this article, we review the contribution of elastin in biological processes involved in atherosclerosis progression from its initial elastase-driven degradation to its ultimate cellular effects. Finally, we discuss the ERC and its derived signaling pathways as promising therapeutic targets

Immune and Smooth Muscle Cells Interactions in Atherosclerosis: How to Target a Breaking Bad Dialogue?

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