{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T23:10:34Z","timestamp":1790550634144,"version":"4.1.0"},"reference-count":58,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,6,22]],"date-time":"2020-06-22T00:00:00Z","timestamp":1592784000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19K17732, 15H05788"],"award-info":[{"award-number":["19K17732, 15H05788"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008695","name":"Japan Foundation for Applied Enzymology","doi-asserted-by":"publisher","award":["none"],"award-info":[{"award-number":["none"]}],"id":[{"id":"10.13039\/100008695","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Renal inflammation is known to be involved in salt-induced renal damage, leading to end-stage renal disease. This study aims to evaluate the role of inflammation in anti-inflammatory and renoprotective effects of beraprost sodium (BPS), a prostaglandin I2 (PGI2) analog, in Dahl salt-sensitive (DS) rats. Five-week-old male DS rats were fed a normal-salt diet (0.5% NaCl), a high-salt diet (8% NaCl), or a high-salt diet plus BPS treatment for 3 weeks. BPS treatment could inhibit marked proteinuria and renal injury in salt-loaded DS rats with elevated blood pressure, accompanied by renal inflammation suppression. Notably, high salt increased renal expression of active Rac1, followed by increased Sgk1 expressions, a downstream molecule of mineralocorticoid receptor (MR) signal, indicating salt-induced activation of Rac1-MR pathway. However, BPS administration inhibited salt-induced Rac1-MR activation as well as renal inflammation and damage, suggesting that Rac1-MR pathway is involved in anti-inflammatory and renoprotective effects of PGI2. Based upon Rac1 activated by inflammation, moreover, BPS inhibited salt-induced activation of Rac1-MR pathway by renal inflammation suppression, resulting in the attenuation of renal damage in salt-loaded DS rats. Thus, BPS is efficacious for the treatment of salt-induced renal injury.<\/jats:p>","DOI":"10.3390\/ijms21124433","type":"journal-article","created":{"date-parts":[[2020,6,23]],"date-time":"2020-06-23T06:11:02Z","timestamp":1592892662000},"page":"4433","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["PGI2 Analog Attenuates Salt-Induced Renal Injury through the Inhibition of Inflammation and Rac1-MR Activation"],"prefix":"10.3390","volume":"21","author":[{"given":"Daigoro","family":"Hirohama","sequence":"first","affiliation":[{"name":"Division of Clinical Epigenetics, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo 153-8904, Japan"},{"name":"Division of Nephrology, Department of Internal Medicine, Teikyo University School of Medicine, Tokyo 173-8606, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wakako","family":"Kawarazaki","sequence":"additional","affiliation":[{"name":"Division of Clinical Epigenetics, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo 153-8904, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9542-847X","authenticated-orcid":false,"given":"Mitsuhiro","family":"Nishimoto","sequence":"additional","affiliation":[{"name":"Division of Clinical Epigenetics, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo 153-8904, Japan"},{"name":"Department of Internal Medicine, International University of Health and Welfare Mita Hospital, Tokyo 108-8329, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiro","family":"Ayuzawa","sequence":"additional","affiliation":[{"name":"Division of Clinical Epigenetics, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo 153-8904, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1650-1734","authenticated-orcid":false,"given":"Takeshi","family":"Marumo","sequence":"additional","affiliation":[{"name":"Division of Clinical Epigenetics, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo 153-8904, Japan"},{"name":"Center for Basic Medical Research at Narita Campus, International University of Health and Welfare, Chiba 286-8686, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeru","family":"Shibata","sequence":"additional","affiliation":[{"name":"Division of Clinical Epigenetics, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo 153-8904, Japan"},{"name":"Division of Nephrology, Department of Internal Medicine, Teikyo University School of Medicine, Tokyo 173-8606, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiro","family":"Fujita","sequence":"additional","affiliation":[{"name":"Division of Clinical Epigenetics, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo 153-8904, Japan"},{"name":"Shinshu University School of Medicine and Research Center for Social Systems, Nagano 389-0111, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"H1018","DOI":"10.1152\/ajpheart.00487.2006","article-title":"Immune suppression prevents renal damage and dysfunction and reduces arterial pressure in salt-sensitive hypertension","volume":"292","author":"Tian","year":"2007","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s11906-018-0903-x","article-title":"Inflammation in Salt-Sensitive Hypertension and Renal Damage","volume":"20","author":"Lu","year":"2018","journal-title":"Curr. Hypertens. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.1038\/s41440-019-0332-5","article-title":"Evaluation of the pathophysiological mechanisms of salt-sensitive hypertension","volume":"42","author":"Hirohama","year":"2019","journal-title":"Hypertens. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1161\/HYPERTENSIONAHA.115.05970","article-title":"Renal protective effect of N-acetyl-seryl-aspartyl-lysyl-proline in dahl salt-sensitive rats","volume":"66","author":"Worou","year":"2015","journal-title":"Hypertension"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/nrneph.2012.282","article-title":"Role of Rac1-mineralocorticoid-receptor signalling in renal and cardiac disease","volume":"9","author":"Nagase","year":"2013","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1038\/nm.1879","article-title":"Modification of mineralocorticoid receptor function by Rac1 GTPase: Implication in proteinuric kidney disease","volume":"14","author":"Shibata","year":"2008","journal-title":"Nat. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3233","DOI":"10.1172\/JCI43124","article-title":"Rac1 GTPase in rodent kidneys is essential for salt-sensitive hypertension via a mineralocorticoid receptor-dependent pathway","volume":"121","author":"Shibata","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1681\/ASN.2013121258","article-title":"Mechanism of salt-sensitive hypertension: Focus on adrenal and sympathetic nervous systems","volume":"25","author":"Fujita","year":"2014","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1016\/S0735-1097(99)00312-5","article-title":"Effect of orally active prostacyclin analogue on survival of outpatients with primary pulmonary hypertension","volume":"34","author":"Nagaya","year":"1999","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1161\/01.CIR.102.4.426","article-title":"Oral Beraprost sodium, a prostaglandin I(2) analogue, for intermittent claudication: A double-blind, randomized, multicenter controlled trial. Beraprost et Claudication Intermittente (BERCI) Research Group","volume":"102","author":"Lievre","year":"2000","journal-title":"Circulation"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S0014-2999(02)01988-X","article-title":"Amelioration by beraprost sodium, a prostacyclin analogue, of established renal dysfunction in rat glomerulonephritis model","volume":"449","author":"Yamada","year":"2002","journal-title":"Eur. J. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.2337\/db09-1432","article-title":"The prostacyclin analog beraprost sodium ameliorates characteristics of metabolic syndrome in obese Zucker (fatty) rats","volume":"59","author":"Sato","year":"2010","journal-title":"Diabetes"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000195722","article-title":"Amelioration of diabetic nephropathy in OLETF rats by prostaglandin I(2) analog, beraprost sodium","volume":"30","author":"Watanabe","year":"2009","journal-title":"Am. J. Nephrol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1690474","DOI":"10.1155\/2016\/1690474","article-title":"The Protective Effect of Beraprost Sodium on Diabetic Nephropathy by Inhibiting Inflammation and p38 MAPK Signaling Pathway in High-Fat Diet\/Streptozotocin-Induced Diabetic Rats","volume":"2016","author":"Peng","year":"2016","journal-title":"Int. J. Endocrinol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.plefa.2009.03.002","article-title":"Effect of beraprost sodium (BPS) in a new rat partial unilateral ureteral obstruction model","volume":"80","author":"Takenaka","year":"2009","journal-title":"Prostaglandins Leukot. Essent. Fatty Acids"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1007\/s00109-019-01769-x","article-title":"Beraprost sodium mitigates renal interstitial fibrosis through repairing renal microvessels","volume":"97","author":"Li","year":"2019","journal-title":"J. Mol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1016\/S0002-9440(10)62352-8","article-title":"A prostacyclin analog prevents radiocontrast nephropathy via phosphorylation of cyclic AMP response element binding protein","volume":"166","author":"Yano","year":"2005","journal-title":"Am. J. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1055\/s-2004-821024","article-title":"A stable prostacyclin analogue reduces high serum TNF-alpha levels in diabetic patients","volume":"112","author":"Fujiwara","year":"2004","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.ejphar.2013.07.032","article-title":"Beraprost sodium improves survival rates in anti-glomerular basement membrane glomerulonephritis and 5\/6 nephrectomized chronic kidney disease rats","volume":"714","author":"Yamaguchi","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"F621","DOI":"10.1152\/ajprenal.00344.2015","article-title":"Mesenchymal stem cell transplantation inhibited high salt-induced activation of the NLRP3 inflammasome in the renal medulla in Dahl S rats","volume":"310","author":"Zhu","year":"2016","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"27634","DOI":"10.1074\/jbc.M003170200","article-title":"The Rac1\/p38 mitogen-activated protein kinase pathway is required for interferon alpha-dependent transcriptional activation but not serine phosphorylation of Stat proteins","volume":"275","author":"Uddin","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"32357","DOI":"10.1074\/jbc.M005638200","article-title":"Tumor necrosis factor-alpha generates reactive oxygen species via a cytosolic phospholipase A2-linked cascade","volume":"275","author":"Woo","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"27709","DOI":"10.1074\/jbc.M009821200","article-title":"Sequential activation of Rac-1, SEK-1\/MKK-4, and protein kinase Cdelta is required for interleukin-6-induced STAT3 Ser-727 phosphorylation and transactivation","volume":"276","author":"Schuringa","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1038\/nrneph.2012.191","article-title":"The role of the kidney in regulating arterial blood pressure","volume":"8","author":"Wadei","year":"2012","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1161\/01.HYP.0000222003.28517.99","article-title":"Podocyte injury underlies the glomerulopathy of Dahl salt-hypertensive rats and is reversed by aldosterone blocker","volume":"47","author":"Nagase","year":"2006","journal-title":"Hypertension"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1161\/01.HYP.0000255636.11931.a2","article-title":"Podocyte as the target for aldosterone: Roles of oxidative stress and Sgk1","volume":"49","author":"Shibata","year":"2007","journal-title":"Hypertension"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/nrneph.2010.30","article-title":"Aldosterone: Effects on the kidney and cardiovascular system","volume":"6","author":"Briet","year":"2010","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/hr.2016.137","article-title":"Mineralocorticoid receptor as a therapeutic target in chronic kidney disease and hypertension","volume":"40","author":"Shibata","year":"2017","journal-title":"Hypertens. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2879","DOI":"10.1093\/ndt\/gfq197","article-title":"Mineralocorticoid receptor activation contributes to salt-induced hypertension and renal injury in prepubertal Dahl salt-sensitive rats","volume":"25","author":"Kawarazaki","year":"2010","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/s41581-019-0248-y","article-title":"Targeting the progression of chronic kidney disease","volume":"16","author":"Lamas","year":"2020","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1038\/s41591-019-0675-0","article-title":"Chronic inflammation in the etiology of disease across the life span","volume":"25","author":"Furman","year":"2019","journal-title":"Nat. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1172\/JCI13350","article-title":"Statins as antioxidant therapy for preventing cardiac myocyte hypertrophy","volume":"108","author":"Takemoto","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"18434","DOI":"10.1074\/jbc.M409710200","article-title":"G alpha 12\/13- and reactive oxygen species-dependent activation of c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase by angiotensin receptor stimulation in rat neonatal cardiomyocytes","volume":"280","author":"Nishida","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1681\/ASN.2011070734","article-title":"Angiotensin II- and salt-induced kidney injury through Rac1-mediated mineralocorticoid receptor activation","volume":"23","author":"Kawarazaki","year":"2012","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1159\/000358758","article-title":"Local mineralocorticoid receptor activation and the role of Rac1 in obesity-related diabetic kidney disease","volume":"126","author":"Yoshida","year":"2014","journal-title":"Nephron Exp. Nephrol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1161\/HYPERTENSIONAHA.111.185520","article-title":"Oxidative stress causes mineralocorticoid receptor activation in rat cardiomyocytes: Role of small GTPase Rac1","volume":"59","author":"Nagase","year":"2012","journal-title":"Hypertension"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1161\/HYPERTENSIONAHA.115.06054","article-title":"Rac1-Mediated Activation of Mineralocorticoid Receptor in Pressure Overload-Induced Cardiac Injury","volume":"67","author":"Ayuzawa","year":"2016","journal-title":"Hypertension"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/nrneph.2015.114","article-title":"Management of hypertension in chronic kidney disease","volume":"11","author":"Townsend","year":"2015","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1080\/21541248.2016.1232583","article-title":"Rho GTPases: Regulation and roles in cancer cell biology","volume":"7","author":"Haga","year":"2016","journal-title":"Small GTPases"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1038\/nrneph.2016.127","article-title":"Podocyte-actin dynamics in health and disease","volume":"12","author":"Perico","year":"2016","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.1038\/s41467-018-04193-w","article-title":"Mutations in six nephrosis genes delineate a pathogenic pathway amenable to treatment","volume":"9","author":"Ashraf","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Koyama, A., Fujita, T., Gejyo, F., Origasa, H., Isono, M., Kurumatani, H., Okada, K., Kanoh, H., Kiriyama, T., and Yamada, S. (2015). Orally active prostacyclin analogue beraprost sodium in patients with chronic kidney disease: A randomized, double-blind, placebo-controlled, phase II dose finding trial. BMC Nephrol., 16.","DOI":"10.1186\/s12882-015-0130-5"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1111\/1744-9987.12840","article-title":"Effects of Sustained-Release Beraprost in Patients With Primary Glomerular Disease or Nephrosclerosis: CASSIOPEIR Study Results","volume":"24","author":"Nakamoto","year":"2020","journal-title":"Ther. Apher. Dial."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1056\/NEJMoa1313731","article-title":"Spironolactone for heart failure with preserved ejection fraction","volume":"370","author":"Pitt","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1161\/CIRCULATIONAHA.114.013255","article-title":"Regional variation in patients and outcomes in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial","volume":"131","author":"Pfeffer","year":"2015","journal-title":"Circulation"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1056\/NEJMc1612601","article-title":"Spironolactone Metabolites in TOPCAT-New Insights into Regional Variation","volume":"376","author":"Desai","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1038\/s41440-018-0201-7","article-title":"Mineralocorticoid receptor blockade suppresses dietary salt-induced ACEI\/ARB-resistant albuminuria in non-diabetic hypertension: A sub-analysis of evaluate study","volume":"42","author":"Nishimoto","year":"2019","journal-title":"Hypertens. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1146\/annurev.physiol.70.113006.100614","article-title":"Physiological regulation of prostaglandins in the kidney","volume":"70","author":"Hao","year":"2008","journal-title":"Annu. Rev. Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1161\/ATVBAHA.110.207449","article-title":"Prostaglandins and inflammation","volume":"31","author":"Ricciotti","year":"2011","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1042\/CS20120651","article-title":"New roles for old pathways? A circuitous relationship between reactive oxygen species and cyclo-oxygenase in hypertension","volume":"126","author":"Hernanz","year":"2014","journal-title":"Clin. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.2174\/1381612053764922","article-title":"Renal effects of non-steroidal anti-inflammatory drugs and selective cyclooxygenase-2 inhibitors","volume":"11","author":"Cheng","year":"2005","journal-title":"Curr. Pharm. Des."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"132ra154","DOI":"10.1126\/scitranslmed.3003787","article-title":"Vascular COX-2 modulates blood pressure and thrombosis in mice","volume":"4","author":"Yu","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"24","DOI":"10.3389\/fphar.2011.00024","article-title":"Prostacyclin: An inflammatory paradox","volume":"2","author":"Stitham","year":"2011","journal-title":"Front. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1161\/01.HYP.5.5.701","article-title":"In vivo production of prostaglandin I2 in Dahl salt-sensitive and salt-resistant rats","volume":"5","author":"Falardeau","year":"1983","journal-title":"Hypertension"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4281","DOI":"10.1172\/JCI81550","article-title":"Inhibition of cyclooxygenase-2 in hematopoietic cells results in salt-sensitive hypertension","volume":"125","author":"Zhang","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/nm.2337","article-title":"Epigenetic modulation of the renal beta-adrenergic-WNK4 pathway in salt-sensitive hypertension","volume":"17","author":"Mu","year":"2011","journal-title":"Nat. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1681\/ASN.2017030243","article-title":"Aldosterone Is Essential for Angiotensin II-Induced Upregulation of Pendrin","volume":"29","author":"Hirohama","year":"2018","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2388","DOI":"10.1681\/ASN.2014070665","article-title":"Diabetes Induces Aberrant DNA Methylation in the Proximal Tubules of the Kidney","volume":"26","author":"Marumo","year":"2015","journal-title":"J. Am. Soc. Nephrol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/12\/4433\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:41:11Z","timestamp":1760175671000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/12\/4433"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,22]]},"references-count":58,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["ijms21124433"],"URL":"https:\/\/doi.org\/10.3390\/ijms21124433","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,22]]}}}