Association between endocrine pancreas and ductal system. More than an epiphenomenon of endocrine differentiation and development?

2sireservedTraditional histological descriptions of the pancreas distinguish between the exocrine and the endocrine pancreas, as if they were two functionally distinct glands. This view has been proven incorrect and can be considered obsolete. Interactions between acinar and islet tissues have been well established through numerous studies that reveal the existence of anatomical and functional relationships between these compartments of the gland. Less attention, however, has traditionally been paid to the relationships occurring between the endocrine pancreas and the ductal system. Associations between islet tissue and ducts are considered by most researchers as only a transient epiphenomenon of endocrine development. This article reviews the evidence that has emerged in the last 10 years demonstrating the existence of stable, close, and systematic relationships between these two pancreatic compartments. Functional and pathophysiological implications are considered, and the existence of an "acinar-duct-islet" axis is put forward. The pancreas appears at present to be an integrated organ composed of three functionally related components of well-orchestrated endocrine and exocrine physiological responses.mixedBERTELLI, Eugenio; BENDAYAN, MoiseBertelli, Eugenio; Bendayan, Mois

Modification of kidney barrier function by the urokinase receptor

9 páginas, 5 figuras, 1 tabla -- PAGS nros. 55-63Podocyte dysfunction, represented by foot process effacement and proteinuria, is often the starting point for progressive kidney disease. Therapies aimed at the cellular level of the disease are currently not available. Here we show that induction of urokinase receptor (uPAR) signaling in podocytes leads to foot process effacement and urinary protein loss via a mechanism that includes lipid-dependent activation of v3 integrin. Mice lacking uPAR (Plaur- /- ) are protected from lipopolysaccharide (LPS)-mediated proteinuria but develop disease after expression of a constitutively active 3 integrin. Gene transfer studies reveal a prerequisite for uPAR expression in podocytes, but not in endothelial cells, for the development of LPS-mediated proteinuria. Mechanistically, uPAR is required to activate v3 integrin in podocytes, promoting cell motility and activation of the small GTPases Cdc42 and Rac1. Blockade of v3 integrin reduces podocyte motility in vitro and lowers proteinuria in mice. Our findings show a physiological role for uPAR signaling in the regulation of kidney permeabilityThis work was supported by US National Institutes of Health (NIH) grants DK073495 (to J.R.), DK057683, DK062472 and the George M. O'Brien Kidney Center DK064236 (to P.M.). C.W. is the Halpin Scholar of the American Society of Nephrology. C.C.M. was supported by a scholarship of the German Academic Exchange Service. M.M.A. was supported by NIH training grant T32DK007540. Gene expression studies of uPAR in human disease were performed in the framework of the European renal cDNA bank. We thank all members of the European Renal cDNA Bank and their patients for their support (for participating centers at the time of the study, see ref. 26). Part of the electron microscopy work was performed in the Microscopy Core facility of the Massachusetts General Hospital Program in Membrane Biology and was supported by an NIH Program Project grant (DK38452)Peer reviewe