Thick ascending limb claudins are altered to increase calciuria and magnesiuria in metabolic acidosis
DC Field | Value | Language |
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dc.contributor.author | Oh, Il Hwan | - |
dc.contributor.author | Jo, Chor Ho | - |
dc.contributor.author | Kim, Sua | - |
dc.contributor.author | Jo, Sungsin | - |
dc.contributor.author | Chung, Sungjin | - |
dc.contributor.author | Kim, Gheun-Ho | - |
dc.date.accessioned | 2021-07-30T04:48:10Z | - |
dc.date.available | 2021-07-30T04:48:10Z | - |
dc.date.created | 2021-07-14 | - |
dc.date.issued | 2021-03 | - |
dc.identifier.issn | 1931-857X | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/1345 | - |
dc.description.abstract | Urinary calcium and magnesium wasting is a characteristic feature of metabolic acidosis, and this study focused on the role of the thick ascending limb of Henle's loop in metabolic acidosis-induced hypercalciuria and hypermagnesiuria because thick ascending limb is an important site of paracellular calcium and magnesium reabsorption. Male Sprague-Dawley rats were used to determine the effects of acid loading (by adding NH4Cl, 7.2 mmol/220 g body wt/day to food slurry for 7 days) on renal expression of claudins and then to evaluate whether the results were reversed by antagonizing calcium-sensing receptor (using NPS-2143). At the end of each animal experiment, the kidneys were harvested for immunoblotting, immunofluorescence micros-copy, and quantitative PCR (qPCR) analysis of claudins and the calcium-sensing receptor. As expected, NH4Cl loading lowered urinary pH and increased excretion of urinary calcium and magnesium. In NH4Cl-loaded rats, renal protein and mRNA expression of claudin-16, and claudin-19, were decreased compared with controls. However, claudin-14 protein and mRNA increased in NH4Cl-loaded rats. Consistently, the calcium-sensing receptor protein and mRNA were up-regulated in NH4Cl-loaded rats. All these changes were reversed by NPS-2143 coadministration and were confirmed using immunofluorescence microscopy. Hypercalciuria and hypermagnesiuria in NH4Cl-loaded rats were significantly ameliorated by NPS-2143 coadministration as well. We conclude that in metabolic acidosis, claudin-16 and claudin-19 in the thick ascending limb are down-regulated to produce hypercalciuria and hypermagnesiuria via the calcium-sensing receptor. NEW & NOTEWORTHY This study found that the thick ascending limb of Henle's loop is involved in the mechanisms of hypercalciuria and hypermagnesiuria in metabolic acidosis. Specifically, expression of claudin-16/19 and claudin-14 was altered via upregulation of calcium-sensing receptor in NH4Cl-induced metabolic acidosis. Our novel findings contribute to understanding the regulatory role of paracellular tight junction proteins in the thick ascending limb. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | AMER PHYSIOLOGICAL SOC | - |
dc.title | Thick ascending limb claudins are altered to increase calciuria and magnesiuria in metabolic acidosis | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, Gheun-Ho | - |
dc.identifier.doi | 10.1152/ajprenal.00282.2020 | - |
dc.identifier.scopusid | 2-s2.0-85102964223 | - |
dc.identifier.wosid | 000630443500010 | - |
dc.identifier.bibliographicCitation | AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, v.320, no.3, pp.F418 - F428 | - |
dc.relation.isPartOf | AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY | - |
dc.citation.title | AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY | - |
dc.citation.volume | 320 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | F418 | - |
dc.citation.endPage | F428 | - |
dc.type.rims | ART | - |
dc.type.docType | Review | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Physiology | - |
dc.relation.journalResearchArea | Urology & Nephrology | - |
dc.relation.journalWebOfScienceCategory | Physiology | - |
dc.relation.journalWebOfScienceCategory | Urology & Nephrology | - |
dc.subject.keywordPlus | SENSING RECEPTOR | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | TRANSPORT | - |
dc.subject.keywordPlus | CA2+ | - |
dc.subject.keywordPlus | REABSORPTION | - |
dc.subject.keywordPlus | MECHANISMS | - |
dc.subject.keywordPlus | PH | - |
dc.subject.keywordPlus | COTRANSPORTER | - |
dc.subject.keywordPlus | PHOSPHATE | - |
dc.subject.keywordPlus | GENE | - |
dc.subject.keywordAuthor | calcium | - |
dc.subject.keywordAuthor | claudin-16 | - |
dc.subject.keywordAuthor | claudin-19 | - |
dc.subject.keywordAuthor | magnesium | - |
dc.subject.keywordAuthor | thick ascending limb | - |
dc.subject.keywordAuthor | tight junction | - |
dc.identifier.url | https://journals.physiology.org/doi/full/10.1152/ajprenal.00282.2020 | - |
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