Megalin/LRP2 Expression Is Induced by Peroxisome Proliferator-Activated Receptor -Alpha and -Gamma: Implications for PPARs' Roles in Renal Function

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dc.contributor.authorCabezas, Felipe
dc.contributor.authorLagos, Jonathan
dc.contributor.authorCespedes, Carlos
dc.contributor.authorVio, Carlos P.
dc.contributor.authorBronfman, Miguel
dc.contributor.authorMarzolo, Maria Paz
dc.date.accessioned2024-01-10T12:40:17Z
dc.date.available2024-01-10T12:40:17Z
dc.date.issued2011
dc.description.abstractBackground: Megalin is a large endocytic receptor with relevant functions during development and adult life. It is expressed at the apical surface of several epithelial cell types, including proximal tubule cells (PTCs) in the kidney, where it internalizes apolipoproteins, vitamins and hormones with their corresponding carrier proteins and signaling molecules. Despite the important physiological roles of megalin little is known about the regulation of its expression. By analyzing the human megalin promoter, we found three response elements for the peroxisomal proliferator-activated receptor (PPAR). The objective of this study was to test whether megalin expression is regulated by the PPARs.
dc.description.abstractMethodology/Principal Findings: Treatment of epithelial cell lines with PPAR alpha or PPAR gamma ligands increased megalin mRNA and protein expression. The stimulation of megalin mRNA expression was blocked by the addition of specific PPAR alpha or PPAR gamma antagonists. Furthermore, PPAR bound to three PPAR response elements located in the megalin promoter, as shown by EMSA, and PPAR alpha and its agonist activated a luciferase construct containing a portion of the megalin promoter and the first response element. Accordingly, the activation of PPAR alpha and PPAR gamma enhanced megalin expression in mouse kidney. As previously observed, high concentrations of bovine serum albumin (BSA) decreased megalin in PTCs in vitro; however, PTCs pretreated with PPAR alpha and PPAR gamma agonists avoided this BSA-mediated reduction of megalin expression. Finally, we found that megalin expression was significantly inhibited in the PTCs of rats that were injected with BSA to induce tubulointerstitial damage and proteinuria. Treatment of these rats with PPAR gamma agonists counteracted the reduction in megalin expression and the proteinuria induced by BSA.
dc.description.abstractConclusions: PPAR alpha/gamma and their agonists positively control megalin expression. This regulation could have an important impact on several megalin-mediated physiological processes and on pathophysiologies such as chronic kidney disease associated with diabetes and hypertension, in which megalin expression is impaired.
dc.description.funderFondecyt (Fondo Nacional de Investigacion Cientifica y Tecnologica, CHILE)
dc.description.funderProyecto Nucleo Milenio
dc.description.funderFondos del Programa Iniciativa Cientifica Milenio (ICM)
dc.format.extent17 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1371/journal.pone.0016794
dc.identifier.issn1932-6203
dc.identifier.pubmedidMEDLINE:21311715
dc.identifier.urihttps://doi.org/10.1371/journal.pone.0016794
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/77292
dc.identifier.wosidWOS:000287036200041
dc.information.autorucCiencias Biológicas;Bronfman M ;S/I;98819
dc.information.autorucCiencias Biológicas;Cabezas F ;S/I;142303
dc.information.autorucCiencias Biológicas;Cespedes C ;S/I;116908
dc.information.autorucMedicina;Lagos J ;S/I;179247
dc.information.autorucCiencias Biológicas;Marzolo MP ;S/I;72595
dc.information.autorucCiencias Biológicas;Vio C;S/I;99575
dc.issue.numero2
dc.language.isoen
dc.nota.accesoSin adjunto
dc.publisherPUBLIC LIBRARY SCIENCE
dc.revistaPLOS ONE
dc.rightsregistro bibliográfico
dc.subjectPROXIMAL TUBULAR CELLS
dc.subjectANGIOTENSIN-II
dc.subjectGENE-EXPRESSION
dc.subjectMEDIATED ENDOCYTOSIS
dc.subjectALBUMIN REABSORPTION
dc.subjectDIABETIC-NEPHROPATHY
dc.subjectKIDNEY-DISEASE
dc.subjectMICE LACKING
dc.subjectFATTY-ACIDS
dc.subjectPIOGLITAZONE
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleMegalin/LRP2 Expression Is Induced by Peroxisome Proliferator-Activated Receptor -Alpha and -Gamma: Implications for PPARs' Roles in Renal Function
dc.typeartículo
dc.volumen6
sipa.codpersvinculados98819
sipa.codpersvinculados142303
sipa.codpersvinculados116908
sipa.codpersvinculados179247
sipa.codpersvinculados72595
sipa.codpersvinculados99575
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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