Routes of Albumin Overload Toxicity in Renal Tubular Epithelial Cells
Besides being a marker of kidney disease severity, albuminuria exerts a toxic effect on renal proximal tubular epithelial cells (RPTECs). We evaluated whether an unfolded protein response (UPR) or DNA damage response (DDR) is elicited in RPTECs exposed to high albumin concentration. The deleterious...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-06-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/11/9640 |
| _version_ | 1797597341034741760 |
|---|---|
| author | Theodoros Eleftheriadis Georgios Pissas Spyridon Golfinopoulos Maria Efthymiadi Christina Poulianiti Maria Anna Polyzou Konsta Vassilios Liakopoulos Ioannis Stefanidis |
| author_facet | Theodoros Eleftheriadis Georgios Pissas Spyridon Golfinopoulos Maria Efthymiadi Christina Poulianiti Maria Anna Polyzou Konsta Vassilios Liakopoulos Ioannis Stefanidis |
| author_sort | Theodoros Eleftheriadis |
| collection | DOAJ |
| description | Besides being a marker of kidney disease severity, albuminuria exerts a toxic effect on renal proximal tubular epithelial cells (RPTECs). We evaluated whether an unfolded protein response (UPR) or DNA damage response (DDR) is elicited in RPTECs exposed to high albumin concentration. The deleterious outcomes of the above pathways, apoptosis, senescence, or epithelial-to-mesenchymal transition (EMT) were evaluated. Albumin caused reactive oxygen species (ROS) overproduction and protein modification, and a UPR assessed the level of crucial molecules involved in this pathway. ROS also induced a DDR evaluated by critical molecules involved in this pathway. Apoptosis ensued through the extrinsic pathway. Senescence also occurred, and the RPTECs acquired a senescence-associated secretory phenotype since they overproduced IL-1β and TGF-β1. The latter may contribute to the observed EMT. Agents against endoplasmic reticulum stress (ERS) only partially alleviated the above changes, while the inhibition of ROS upregulation prevented both UPR and DDR and all the subsequent harmful effects. Briefly, albumin overload causes cellular apoptosis, senescence, and EMT in RPTECs by triggering UPR and DDR. Promising anti-ERS factors are beneficial but cannot eliminate the albumin-induced deleterious effects because DDR also occurs. Factors that suppress ROS overproduction may be more effective since they could halt UPR and DDR. |
| first_indexed | 2024-03-11T03:04:52Z |
| format | Article |
| id | doaj.art-9de65a2b3cca4fd785f88309c03eb607 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T03:04:52Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9de65a2b3cca4fd785f88309c03eb6072023-11-18T08:01:54ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-012411964010.3390/ijms24119640Routes of Albumin Overload Toxicity in Renal Tubular Epithelial CellsTheodoros Eleftheriadis0Georgios Pissas1Spyridon Golfinopoulos2Maria Efthymiadi3Christina Poulianiti4Maria Anna Polyzou Konsta5Vassilios Liakopoulos6Ioannis Stefanidis7Department of Nephrology, Faculty of Medicine, University of Thessaly, Biopolis, Mezourlo Hill, 41110 Larissa, GreeceDepartment of Nephrology, Faculty of Medicine, University of Thessaly, Biopolis, Mezourlo Hill, 41110 Larissa, GreeceDepartment of Nephrology, Faculty of Medicine, University of Thessaly, Biopolis, Mezourlo Hill, 41110 Larissa, GreeceDepartment of Nephrology, Faculty of Medicine, University of Thessaly, Biopolis, Mezourlo Hill, 41110 Larissa, GreeceDepartment of Nephrology, Faculty of Medicine, University of Thessaly, Biopolis, Mezourlo Hill, 41110 Larissa, GreeceDepartment of Nephrology, Faculty of Medicine, University of Thessaly, Biopolis, Mezourlo Hill, 41110 Larissa, GreeceDepartment of Nephrology, Faculty of Medicine, University of Thessaly, Biopolis, Mezourlo Hill, 41110 Larissa, GreeceDepartment of Nephrology, Faculty of Medicine, University of Thessaly, Biopolis, Mezourlo Hill, 41110 Larissa, GreeceBesides being a marker of kidney disease severity, albuminuria exerts a toxic effect on renal proximal tubular epithelial cells (RPTECs). We evaluated whether an unfolded protein response (UPR) or DNA damage response (DDR) is elicited in RPTECs exposed to high albumin concentration. The deleterious outcomes of the above pathways, apoptosis, senescence, or epithelial-to-mesenchymal transition (EMT) were evaluated. Albumin caused reactive oxygen species (ROS) overproduction and protein modification, and a UPR assessed the level of crucial molecules involved in this pathway. ROS also induced a DDR evaluated by critical molecules involved in this pathway. Apoptosis ensued through the extrinsic pathway. Senescence also occurred, and the RPTECs acquired a senescence-associated secretory phenotype since they overproduced IL-1β and TGF-β1. The latter may contribute to the observed EMT. Agents against endoplasmic reticulum stress (ERS) only partially alleviated the above changes, while the inhibition of ROS upregulation prevented both UPR and DDR and all the subsequent harmful effects. Briefly, albumin overload causes cellular apoptosis, senescence, and EMT in RPTECs by triggering UPR and DDR. Promising anti-ERS factors are beneficial but cannot eliminate the albumin-induced deleterious effects because DDR also occurs. Factors that suppress ROS overproduction may be more effective since they could halt UPR and DDR.https://www.mdpi.com/1422-0067/24/11/9640albuminrenal tubular epithelial cellsendoplasmic reticulum stressDNA damageapoptosissenescence |
| spellingShingle | Theodoros Eleftheriadis Georgios Pissas Spyridon Golfinopoulos Maria Efthymiadi Christina Poulianiti Maria Anna Polyzou Konsta Vassilios Liakopoulos Ioannis Stefanidis Routes of Albumin Overload Toxicity in Renal Tubular Epithelial Cells International Journal of Molecular Sciences albumin renal tubular epithelial cells endoplasmic reticulum stress DNA damage apoptosis senescence |
| title | Routes of Albumin Overload Toxicity in Renal Tubular Epithelial Cells |
| title_full | Routes of Albumin Overload Toxicity in Renal Tubular Epithelial Cells |
| title_fullStr | Routes of Albumin Overload Toxicity in Renal Tubular Epithelial Cells |
| title_full_unstemmed | Routes of Albumin Overload Toxicity in Renal Tubular Epithelial Cells |
| title_short | Routes of Albumin Overload Toxicity in Renal Tubular Epithelial Cells |
| title_sort | routes of albumin overload toxicity in renal tubular epithelial cells |
| topic | albumin renal tubular epithelial cells endoplasmic reticulum stress DNA damage apoptosis senescence |
| url | https://www.mdpi.com/1422-0067/24/11/9640 |
| work_keys_str_mv | AT theodoroseleftheriadis routesofalbuminoverloadtoxicityinrenaltubularepithelialcells AT georgiospissas routesofalbuminoverloadtoxicityinrenaltubularepithelialcells AT spyridongolfinopoulos routesofalbuminoverloadtoxicityinrenaltubularepithelialcells AT mariaefthymiadi routesofalbuminoverloadtoxicityinrenaltubularepithelialcells AT christinapoulianiti routesofalbuminoverloadtoxicityinrenaltubularepithelialcells AT mariaannapolyzoukonsta routesofalbuminoverloadtoxicityinrenaltubularepithelialcells AT vassiliosliakopoulos routesofalbuminoverloadtoxicityinrenaltubularepithelialcells AT ioannisstefanidis routesofalbuminoverloadtoxicityinrenaltubularepithelialcells |