Obiettivo Hypertension, or elevated arterial blood pressure, is a significant global health concern. A major cause of hypertension is the abnormality in salt (NaCl) handling in distal nephron segments within kidney. Although there has been long a debate with regard to the relative importance of Na+ vs. Cl- in inducing salt-sensitive hypertension, previous research demonstrated that excess intake of Cl- could lead to severe salt-sensitive hypertension. Thus, better understanding on molecular mechanisms of renal Cl- handling would provide useful insights in treatment of hypertension. Previous studies largely focused on the identification and regulation of apically expressed Cl- transporters, including Na+-Cl- cotransporter, Na+-K+-2Cl- cotransporter (NKCC1/NKCC2) and pendrin, but mechanisms and regulation of Cl- transporters on basolateral membranes (i.e. an exit of Cl- into the interstitial space) remains poorly described. Thus, the current proposal will investigate the physiological role of basolateral Cl- channel distributed in distal nephron, specifically ClC-kb. Using a transgenic ClC-kb knockout line of mice, I propose to investigate the physiological role of this channel within isolated tubule and at the whole animal level. In addition, ClC-kb channel is known to interact with a functional β-subunit, barttin, and this interaction could affect Cl- conductance. I propose to investigate the molecular mechanisms by which barttin can affect ClC-kb-mediated chloride transport. The proposed studies will shed new insights into the molecular mechanisms of Cl- reabsorption in distal nephron, and could provide a basis for novel approach in treatment of hypertension. Parole chiave Hypertension Ion transport Chloride Channels Sodium transport Kidney Programma(i) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Argomento(i) MSCA-IF-2014-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Invito a presentare proposte H2020-MSCA-IF-2014 Vedi altri progetti per questo bando Meccanismo di finanziamento MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinatore INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE Contribution nette de l'UE € 173 076,00 Indirizzo RUE DE TOLBIAC 101 75654 Paris Francia Mostra sulla mappa Regione Ile-de-France Ile-de-France Paris Tipo di attività Research Organisations Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 173 076,00
