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首页> 外文期刊>EBioMedicine >Salt-deficient diet exacerbates cystogenesis in ARPKD via epithelial sodium channel (ENaC)
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Salt-deficient diet exacerbates cystogenesis in ARPKD via epithelial sodium channel (ENaC)

机译：缺盐饮食会通过上皮钠通道（ENaC）加剧ARPKD中的囊肿生成

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Background 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. Methods 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. Findings 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 Nasup+/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. Interpretation 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.
机译：背景常染色体隐性隐性多囊肾病（ARPKD）的特征是主要在收集管（CD）系统中的肾小管中形成囊肿，最终导致终末期肾脏疾病。一般建议PKD患者限制饮食中钠的摄入量。这项研究旨在测试ARPKD中饮食盐处理的结果。方法PCK / CrljCrlPkhd1pck / CRL（PCK）大鼠（ARPKD模型）饲喂正常（0.4％NaCl; NS），高盐（4％NaCl; HS）和钠缺乏（0.01％NaCl; SD）饮食持续8周。免疫组织化学，GFR测量，平衡研究和分子生物学方法被用于评估方案的结果。使用LC-MS / MS评估肾素-血管紧张素-醛固酮系统（RAAS）的水平，并研究肾脏miRNA谱。研究结果HS和SD饮食均导致了囊肿发生的增加。然而，SD饮食导致肾皮质区域内的囊肿大量生长，并导致组织肥大。 SD组的RAAS组件得到增强。我们观察到SD组上皮Na + 通道（ENaC）表达减少，同时mRNA水平升高。 miRNA检测显示，SD组肾脏miR-9a-5p水平升高;我们证明了这种miRNA减少了CD细胞中的ENaC通道数。解释我们的数据证明了在盐限制期间ARPKD进展的机制涉及ENaC的活性。我们进一步表明，miR-9a-5p可能与这种机制有关，并且miR-9a-5p下调培养的CD细胞中的ENaC。我们的发现开启了新的治疗可能性，并突出了了解ARPKD中盐重吸收的重要性。

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