Human parietal epithelial cells as Trojan horses in albumin overload
Abstract Parietal Epithelial Cells (PECs) activation and proliferation are common to several distinct forms of glomerulopathies. Due to several stimuli, PECs can change to a progenitor (CD24+ and CD133/2+) or a pro-sclerotic (CD44+) phenotype. In addition, PECs, which are constantly exposed to filte...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-024-84972-2 |
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| author | Giovanna Priante Monica Ceol Lisa Gianesello Claudia Maria Radu Rachele Mantese Lucia Federica Stefanelli Martina Cacciapuoti Francesca K. Martino Lorenzo Arcangelo Calò Franca Anglani Federico Nalesso Dorella Del Prete |
| author_facet | Giovanna Priante Monica Ceol Lisa Gianesello Claudia Maria Radu Rachele Mantese Lucia Federica Stefanelli Martina Cacciapuoti Francesca K. Martino Lorenzo Arcangelo Calò Franca Anglani Federico Nalesso Dorella Del Prete |
| author_sort | Giovanna Priante |
| collection | DOAJ |
| description | Abstract Parietal Epithelial Cells (PECs) activation and proliferation are common to several distinct forms of glomerulopathies. Due to several stimuli, PECs can change to a progenitor (CD24+ and CD133/2+) or a pro-sclerotic (CD44+) phenotype. In addition, PECs, which are constantly exposed to filtered albumin, are known to be involved in albumin internalization, but how this mechanism occurs is unknown. We hypothesized that PECs can transport albumin via receptor-mediated endocytosis and that albumin overload may affect the state of PECs. Conditionally immortalized human PECs (hPECs) were incubated with different albumin concentrations at different times. Albumin internalization studies were performed. Protein expression was assessed using In-Cell Western and immunofluorescence. Cell morphology was analyzed by phase-contrast microscopy and F-actin staining. We demonstrate that hPECs internalize albumin via receptor-mediated mechanisms. Under albumin stimulation, megalin, cubilin, ClC-5, CD133/2, CD24, and CD44 were upregulated. The increase of pERK1/2, the upregulation of ROCK1, ROCK2, caspase -3, -6, and -7, and the morphological changes associated with loss of F-actin fibers indicated that inflammation, proliferation and apoptosis mechanisms had been activated. Our results demonstrate that long-term exposure to high doses of albumin induces up-regulation of molecules involved in the tubular protein uptake machinery and suggest that albumin overload is able to trigger a regenerative process as well as an activation state which might lead in vivo to glomerular crescent formation. |
| format | Article |
| id | doaj-art-633cec2a5b944d97acfa97ed6746811d |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-633cec2a5b944d97acfa97ed6746811d2025-01-19T12:23:08ZengNature PortfolioScientific Reports2045-23222025-01-0115111710.1038/s41598-024-84972-2Human parietal epithelial cells as Trojan horses in albumin overloadGiovanna Priante0Monica Ceol1Lisa Gianesello2Claudia Maria Radu3Rachele Mantese4Lucia Federica Stefanelli5Martina Cacciapuoti6Francesca K. Martino7Lorenzo Arcangelo Calò8Franca Anglani9Federico Nalesso10Dorella Del Prete11Kidney Histomorphology and Molecular Biology Laboratory, Nephrology Unit, Department of Medicine - DIMED, University of PaduaKidney Histomorphology and Molecular Biology Laboratory, Nephrology Unit, Department of Medicine - DIMED, University of PaduaKidney Histomorphology and Molecular Biology Laboratory, Nephrology Unit, Department of Medicine - DIMED, University of PaduaThrombotic and Haemorrhagic Diseases Unit, Department of Medicine-DIMED, University of PaduaKidney Histomorphology and Molecular Biology Laboratory, Nephrology Unit, Department of Medicine - DIMED, University of PaduaKidney Histomorphology and Molecular Biology Laboratory, Nephrology Unit, Department of Medicine - DIMED, University of PaduaKidney Histomorphology and Molecular Biology Laboratory, Nephrology Unit, Department of Medicine - DIMED, University of PaduaKidney Histomorphology and Molecular Biology Laboratory, Nephrology Unit, Department of Medicine - DIMED, University of PaduaKidney Histomorphology and Molecular Biology Laboratory, Nephrology Unit, Department of Medicine - DIMED, University of PaduaKidney Histomorphology and Molecular Biology Laboratory, Nephrology Unit, Department of Medicine - DIMED, University of PaduaKidney Histomorphology and Molecular Biology Laboratory, Nephrology Unit, Department of Medicine - DIMED, University of PaduaKidney Histomorphology and Molecular Biology Laboratory, Nephrology Unit, Department of Medicine - DIMED, University of PaduaAbstract Parietal Epithelial Cells (PECs) activation and proliferation are common to several distinct forms of glomerulopathies. Due to several stimuli, PECs can change to a progenitor (CD24+ and CD133/2+) or a pro-sclerotic (CD44+) phenotype. In addition, PECs, which are constantly exposed to filtered albumin, are known to be involved in albumin internalization, but how this mechanism occurs is unknown. We hypothesized that PECs can transport albumin via receptor-mediated endocytosis and that albumin overload may affect the state of PECs. Conditionally immortalized human PECs (hPECs) were incubated with different albumin concentrations at different times. Albumin internalization studies were performed. Protein expression was assessed using In-Cell Western and immunofluorescence. Cell morphology was analyzed by phase-contrast microscopy and F-actin staining. We demonstrate that hPECs internalize albumin via receptor-mediated mechanisms. Under albumin stimulation, megalin, cubilin, ClC-5, CD133/2, CD24, and CD44 were upregulated. The increase of pERK1/2, the upregulation of ROCK1, ROCK2, caspase -3, -6, and -7, and the morphological changes associated with loss of F-actin fibers indicated that inflammation, proliferation and apoptosis mechanisms had been activated. Our results demonstrate that long-term exposure to high doses of albumin induces up-regulation of molecules involved in the tubular protein uptake machinery and suggest that albumin overload is able to trigger a regenerative process as well as an activation state which might lead in vivo to glomerular crescent formation.https://doi.org/10.1038/s41598-024-84972-2hPECsAlbuminClC-5MegalinCubilinCD44 |
| spellingShingle | Giovanna Priante Monica Ceol Lisa Gianesello Claudia Maria Radu Rachele Mantese Lucia Federica Stefanelli Martina Cacciapuoti Francesca K. Martino Lorenzo Arcangelo Calò Franca Anglani Federico Nalesso Dorella Del Prete Human parietal epithelial cells as Trojan horses in albumin overload Scientific Reports hPECs Albumin ClC-5 Megalin Cubilin CD44 |
| title | Human parietal epithelial cells as Trojan horses in albumin overload |
| title_full | Human parietal epithelial cells as Trojan horses in albumin overload |
| title_fullStr | Human parietal epithelial cells as Trojan horses in albumin overload |
| title_full_unstemmed | Human parietal epithelial cells as Trojan horses in albumin overload |
| title_short | Human parietal epithelial cells as Trojan horses in albumin overload |
| title_sort | human parietal epithelial cells as trojan horses in albumin overload |
| topic | hPECs Albumin ClC-5 Megalin Cubilin CD44 |
| url | https://doi.org/10.1038/s41598-024-84972-2 |
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