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Mycophenolic acid directly protects podocytes by preserving the actin cytoskeleton and increasing cell survival.
Abo Zed, Seif El Din; Hackl, Agnes; Bohl, Katrin; Ebert, Lena; Kieckhöfer, Emilia; Müller, Carsten; Becker, Kerstin; Fink, Gregor; Nüsken, Kai-Dietrich; Nüsken, Eva; Müller, Roman-Ulrich; Schermer, Bernhard; Weber, Lutz T.
Afiliación
  • Abo Zed SED; Faculty of Medicine and University Hospital Cologne, Department of Pediatrics, University of Cologne, Cologne, Germany.
  • Hackl A; Faculty of Medicine and University Hospital Cologne, Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
  • Bohl K; Faculty of Medicine and University Hospital Cologne, Department of Pediatrics, University of Cologne, Cologne, Germany. agnes.hackl@uk-koeln.de.
  • Ebert L; Faculty of Medicine and University Hospital Cologne, Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany. agnes.hackl@uk-koeln.de.
  • Kieckhöfer E; Faculty of Medicine and University Hospital Cologne, Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
  • Müller C; Cologne Cluster of Excellence on Cellular Stress Responses in Ageing-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
  • Becker K; Faculty of Medicine and University Hospital Cologne, Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
  • Fink G; Cologne Cluster of Excellence on Cellular Stress Responses in Ageing-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
  • Nüsken KD; Faculty of Medicine and University Hospital Cologne, Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
  • Nüsken E; Cologne Cluster of Excellence on Cellular Stress Responses in Ageing-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
  • Müller RU; Faculty of Medicine and University Hospital Cologne, Pharmacology at the Laboratory Center, Department of Therapeutic Drug Monitoring DE, University of Cologne, Cologne, Germany.
  • Schermer B; Faculty of Medicine and University Hospital Cologne, Cologne Center for Genomics (CCG), University of Cologne, Cologne, Germany.
  • Weber LT; Faculty of Medicine and University Hospital Cologne, Department of Pediatrics, University of Cologne, Cologne, Germany.
Sci Rep ; 13(1): 4281, 2023 03 15.
Article en En | MEDLINE | ID: mdl-36922538
Mycophenolate Mofetil (MMF) has an established role as a therapeutic agent in childhood nephrotic syndrome. While other immunosuppressants have been shown to positively affect podocytes, direct effects of MMF on podocytes remain largely unknown. The present study examines the effects of MMF's active component Mycophenolic Acid (MPA) on the transcriptome of podocytes and investigates its biological significance. We performed transcriptomics in cultured murine podocytes exposed to MPA to generate hypotheses on podocyte-specific effects of MPA. Accordingly, we further analyzed biological MPA effects on actin cytoskeleton morphology after treatment with bovine serum albumin (BSA) by immunofluorescence staining, as well as on cell survival following exposure to TNF-α and cycloheximide by neutral red assay. MPA treatment significantly (adjusted p < 0.05) affected expression of 351 genes in podocytes. Gene Ontology term enrichment analysis particularly clustered terms related to actin and inflammation-related cell death. Indeed, quantification of the actin cytoskeleton of BSA treated podocytes revealed a significant increase of thickness and number of actin filaments after treatment with MPA. Further, MPA significantly reduced TNFα and cycloheximide induced cell death. MPA has a substantial effect on the transcriptome of podocytes in vitro, particularly including functional clusters related to non-immune cell dependent mechanisms. This may provide a molecular basis for direct beneficial effects of MPA on the structural integrity and survival of podocytes under pro-inflammatory conditions.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Podocitos / Ácido Micofenólico Límite: Animals Idioma: En Revista: Sci Rep Año: 2023 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Podocitos / Ácido Micofenólico Límite: Animals Idioma: En Revista: Sci Rep Año: 2023 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido