{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T23:02:25Z","timestamp":1789513345745,"version":"build-2803163510"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","award":["E26\/200.005\/2018"],"award-info":[{"award-number":["E26\/200.005\/2018"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","award":["E26\/211.576\/2021"],"award-info":[{"award-number":["E26\/211.576\/2021"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Albuminuria is a hallmark of kidney disease progression and is associated with impaired glomerular and proximal tubule albumin handling. Efficient receptor-mediated endocytosis and intracellular protein processing in proximal tubule cells require endosomal acidification, a process that depends on multiple transporters, including Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), and its functional interaction with vacuolar H\n                      <jats:sup>+<\/jats:sup>\n                      -ATPase (V-ATPase). However, whether albumin overload directly affects CFTR expression and albumin handling in proximal tubule cells remains unclear. Thus, this study aimed to determine the effects of albumin overload on CFTR and V-ATPase expression, as well as on albumin uptake and degradation, using an\n                      <jats:italic>in vitro<\/jats:italic>\n                      model of porcine proximal tubule cells (LLC-PK1).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>LLC-PK1 were exposed to low (0.1\u00a0mg\/mL) or high (20\u00a0mg\/mL; overload) concentrations of Bovine Serum Albumin (BSA) for 24 or 48\u00a0h. CFTR and V-ATPase protein expression were evaluated by Western blotting. Albumin uptake and degradation were assessed using FITC-conjugated BSA (BSA-FITC). CFTR cellular staining was analyzed by confocal immunofluorescence microscopy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Exposure to 20\u00a0mg\/mL BSA significantly reduced CFTR expression after both 24 and 48\u00a0h, whereas no effects were observed after incubation with a low albumin concentration. V-ATPase expression was significantly reduced only after 48\u00a0h of albumin overload. High albumin concentrations also decreased BSA-FITC uptake, with a greater inhibitory effect observed after 48\u00a0h of treatment. Furthermore, albumin-overloaded cells exhibited impaired intracellular degradation of endocytosed BSA-FITC, as demonstrated by sustained fluorescence intensity and an increased area under the degradation curve. Confocal microscopy revealed reduced CFTR fluorescence intensity under albumin overload conditions, but no evident alterations in its overall subcellular distribution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>BSA overload coordinately downregulates CFTR and V-ATPase expression and is associated with impaired albumin endocytosis and degradation in proximal tubule cells. These findings reveal a novel association between albumin overload and downregulation of CFTR and V-ATPase proteins in proximal tubule cells. Although the present data are correlative and do not establish a direct causal link between CFTR downregulation and the observed functional defects, they suggest that CFTR\/V-ATPase dysregulation may contribute to defective albumin handling under proteinuric conditions and provide a rationale for future mechanistic investigations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1916632","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T22:10:25Z","timestamp":1789510225000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Albumin overload reduces CFTR and V-ATPase expression and impairs albumin endocytosis and degradation in a renal proximal tubule cell line"],"prefix":"10.3389","volume":"17","author":[{"given":"Rodrigo Alves da Silva","family":"Peres","sequence":"first","affiliation":[{"name":"Grupo de Pesquisa em Fisiologia Aplicada e Comparada, Laborat\u00f3rio Integrado de Ci\u00eancias Morfofuncionais, Instituto de Biodiversidade e Sustentabilidade NUPEM, Universidade Federal do Rio de Janeiro","place":["Maca\u00e9, Brazil"]},{"name":"Laborat\u00f3rio: Bioqu\u00edmica e Sinaliza\u00e7\u00e3o Celular, Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Alberto de Souza","family":"Filho","sequence":"additional","affiliation":[{"name":"Grupo de Pesquisa em Fisiologia Aplicada e Comparada, Laborat\u00f3rio Integrado de Ci\u00eancias Morfofuncionais, Instituto de Biodiversidade e Sustentabilidade NUPEM, Universidade Federal do Rio de Janeiro","place":["Maca\u00e9, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo P.","family":"Silva-Aguiar","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio: Bioqu\u00edmica e Sinaliza\u00e7\u00e3o Celular, Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia Yelimar Palmero","family":"Quintana","sequence":"additional","affiliation":[{"name":"Grupo de Pesquisa em Fisiologia Aplicada e Comparada, Laborat\u00f3rio Integrado de Ci\u00eancias Morfofuncionais, Instituto de Biodiversidade e Sustentabilidade NUPEM, Universidade Federal do Rio de Janeiro","place":["Maca\u00e9, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel Carvalho","family":"Castiglione","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa Cl\u00ednicas e Experimentais em Biologia Vascular, Departamento de Ci\u00eancias Fisiol\u00f3gicas, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Oliveira de Souza","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Fisiologia Renal, Departamento de Fisiologia, Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade de S\u00e3o Paulo","place":["S\u00e3o Paulo, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo Marcos","family":"Morales","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Fisiologia Celular e Molecular, Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celso","family":"Caruso-Neves","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio: Bioqu\u00edmica e Sinaliza\u00e7\u00e3o Celular, Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jackson","family":"de Souza-Menezes","sequence":"additional","affiliation":[{"name":"Grupo de Pesquisa em Fisiologia Aplicada e Comparada, Laborat\u00f3rio Integrado de Ci\u00eancias Morfofuncionais, Instituto de Biodiversidade e Sustentabilidade NUPEM, Universidade Federal do Rio de Janeiro","place":["Maca\u00e9, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2066","DOI":"10.1046\/J.1523-1755.2002.00380.X","article-title":"Proximal tubular cells promote fibrogenesis by TGF-\u03b21\u2013mediated induction of peritubular myofibroblasts","volume":"61","author":"Abbate","year":"2002","journal-title":"Kidney Int."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2974","DOI":"10.1681\/ASN.2006040377","article-title":"How does proteinuria cause progressive renal damage?","volume":"17","author":"Abbate","year":"2006","journal-title":"J. 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