{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ilatovskaya DV"],"funding":["American Heart Association","BLRD VA","National Institute of Health grants","NIDDK NIH HHS","NCRR NIH HHS","NHLBI NIH HHS","PKD Foundation","Baltimore PKD Center","Department of Veteran Affairs"],"pagination":["663-674"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6413684"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["40"],"pubmed_abstract":["<h4>Background</h4>Autosomal Recessive Polycystic Kidney Disease (ARPKD) is marked by cyst formation in the renal tubules, primarily in the collecting duct (CD) system, ultimately leading to end-stage renal disease. Patients with PKD are generally advised to restrict their dietary sodium intake. This study was aimed at testing the outcomes of dietary salt manipulation in ARPKD.<h4>Methods</h4>PCK/CrljCrlPkhd1pck/CRL (PCK) rats, a model of ARPKD, were fed a normal (0.4% NaCl; NS), high salt (4% NaCl; HS), and sodium-deficient (0.01% NaCl; SD) diets for 8 weeks. Immunohistochemistry, GFR measurements, balance studies, and molecular biology approaches were applied to evaluate the outcomes of the protocol. Renin-angiotensin-aldosterone system (RAAS) levels were assessed using LC-MS/MS, and renal miRNA profiles were studied.<h4>Findings</h4>Both HS and SD diets resulted in an increase in cystogenesis. However, SD diet caused extensive growth of cysts in the renal cortical area, and hypertrophy of the tissue; RAAS components were enhanced in the SD group. We observed a reduction in epithelial Na<sup>+</sup> channel (ENaC) expression in the SD group, accompanied with mRNA level increase. miRNA assay revealed that renal miR-9a-5p level was augmented in the SD group; we showed that this miRNA decreases ENaC channel number in CD cells.<h4>Interpretation</h4>Our data demonstrate a mechanism of ARPKD progression during salt restriction that involves activity of ENaC. We further show that miR-9a-5p potentially implicated in this mechanism and that miR-9a-5p downregulates ENaC in cultured CD cells. Our findings open new therapeutic possibilities and highlight the importance of understanding salt reabsorption in ARPKD."],"journal":["EBioMedicine"],"pubmed_title":["Salt-deficient diet exacerbates cystogenesis in ARPKD via epithelial sodium channel (ENaC)."],"pmcid":["PMC6413684"],"funding_grant_id":["16EIA26720006 (AS)","P30 DK090868","T32 HL134643 (CAK)","P01 HL116264 (AS)","T32 HL134643","R00 HL116603","221G18a (DVI)","I01 BX004024 (AS)","R00 DK105160","R00 DK105160 (DVI)","R35 HL135749","I01 BX004024","R00 HL116603 (TSP)","M01 RR000058","DK090868"],"pubmed_authors":["Pavlov TS","Isaeva E","Klemens CA","Staruschenko A","Johnson J","Levchenko V","Ilatovskaya DV","Liu P","Kriegel AJ"],"additional_accession":[]},"is_claimable":false,"name":"Salt-deficient diet exacerbates cystogenesis in ARPKD via epithelial sodium channel (ENaC).","description":"<h4>Background</h4>Autosomal Recessive Polycystic Kidney Disease (ARPKD) is marked by cyst formation in the renal tubules, primarily in the collecting duct (CD) system, ultimately leading to end-stage renal disease. Patients with PKD are generally advised to restrict their dietary sodium intake. This study was aimed at testing the outcomes of dietary salt manipulation in ARPKD.<h4>Methods</h4>PCK/CrljCrlPkhd1pck/CRL (PCK) rats, a model of ARPKD, were fed a normal (0.4% NaCl; NS), high salt (4% NaCl; HS), and sodium-deficient (0.01% NaCl; SD) diets for 8 weeks. Immunohistochemistry, GFR measurements, balance studies, and molecular biology approaches were applied to evaluate the outcomes of the protocol. Renin-angiotensin-aldosterone system (RAAS) levels were assessed using LC-MS/MS, and renal miRNA profiles were studied.<h4>Findings</h4>Both HS and SD diets resulted in an increase in cystogenesis. However, SD diet caused extensive growth of cysts in the renal cortical area, and hypertrophy of the tissue; RAAS components were enhanced in the SD group. We observed a reduction in epithelial Na<sup>+</sup> channel (ENaC) expression in the SD group, accompanied with mRNA level increase. miRNA assay revealed that renal miR-9a-5p level was augmented in the SD group; we showed that this miRNA decreases ENaC channel number in CD cells.<h4>Interpretation</h4>Our data demonstrate a mechanism of ARPKD progression during salt restriction that involves activity of ENaC. We further show that miR-9a-5p potentially implicated in this mechanism and that miR-9a-5p downregulates ENaC in cultured CD cells. Our findings open new therapeutic possibilities and highlight the importance of understanding salt reabsorption in ARPKD.","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Feb","modification":"2025-04-19T19:15:10.535Z","creation":"2019-08-04T07:12:03Z"},"accession":"S-EPMC6413684","cross_references":{"pubmed":["30745171"],"doi":["10.1016/j.ebiom.2019.01.006"]}}