Autori: Patrizia Lombari (1), Massimo Mallardo (2), Joseph Amruthraj Nagoth (1), Oriana Petrazzuolo (1), Giuseppe Fiume (3), Roberto Scanni (1), Anna Iervolino (4), Diego Ingrosso (5) Giovambattista Capasso (1, 4)
Affiliazioni: (1) Cattedra di Nefrologia Dipartimento di Scienze Cardio-toraciche e respiratorie, Università degli studi della Campania “Luigi Vanvitelli”, Napoli (2) Dipartimento di Medicina molecolare e Biotecnologie mediche, Università degli studi di Napoli “Federico II”,Italia, (3) Dipartimento di Medicina Sperimentale e Clinica, Università Magna Grecia di Catanzaro, Italia, (4) IRGS, Biogem, Via Camporeale, 83031, Ariano Irpino, Avellino, Italia, (5) Dipartimento di Biochimica, Biofisica e Patologia Generale, Università degli studi della Campania “Luigi Vanvitelli”, Napoli, Italia
The kidney is one of the principle candidate organs involved in the etiology of essential hypertension. In particular, the medullary thick ascending limb (MTAL) of kidney is important in maintaining acid-base balance by reabsorbing most of the filtered bicarbonate, which is not reabsorbed by the proximal tubule. Microarray expression profiling studies in human revealed different expression profiles of microRNAs in hypertensive vs normotensive patients. In this study, we analyzed miRNA expression profiles in isolated MTAL taken from high sodium intake induced hypertensive rats (HSD) versus their normotensive counter parts (NSD). We have identified seven miRNAs, involved in the onset of salt sensitive hypertension, among them one was the most strongly down-regulated. We identified the sodium-hydrogen antiporter 1 (NHE1) mRNA as a putative target of this miRNA, by in silico analysis. Our data showed that this miRNA is downregulated in the MTAL of HSD rats while NHE1 is upregulated, we also checked whether the levels of protein NHE1 could be lowered by overexpression of the identified miRNA. To verify this hypothesis we overexpressed this miRNA in MTAL cell line, by retroviral infection, and observed a downregulation of NHE1 protein. In conclusion our result indicate NHE1 as a target of the identified miRNA and that the expression of this miRNA is influenced by high sodium intake in thick ascending limbs of rats.
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