The integrin repertoire drives YAP-dependent epithelial:stromal interactions during injury of the kidney glomerulus
Abstract The kidney glomerulus is a filtration barrier in which capillary loop architecture depends on epithelial-stromal interactions between podocytes and mesangial cells. Podocytes are terminally differentiated cells within the glomerulus that express YAP and TAZ. Here we test the hypotheses that...
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| Format: | Article |
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Nature Portfolio
2025-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-58567-y |
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| author | Evelyne Huynh-Cong Victoria Driscoll Sandrine Ettou Keith Keller Amha Atakilit Mary E. Taglienti Saurabh Kumar Astrid Weins Valerie A. Schumacher Jordan A. Kreidberg |
| author_facet | Evelyne Huynh-Cong Victoria Driscoll Sandrine Ettou Keith Keller Amha Atakilit Mary E. Taglienti Saurabh Kumar Astrid Weins Valerie A. Schumacher Jordan A. Kreidberg |
| author_sort | Evelyne Huynh-Cong |
| collection | DOAJ |
| description | Abstract The kidney glomerulus is a filtration barrier in which capillary loop architecture depends on epithelial-stromal interactions between podocytes and mesangial cells. Podocytes are terminally differentiated cells within the glomerulus that express YAP and TAZ. Here we test the hypotheses that YAP and TAZ are required in podocytes to maintain capillary loop architecture and that shifts in the integrin repertoire during podocyte injury affect transcriptional activity of YAP and TAZ. Loss of YAP in podocytes of adult mice renders them more sensitive to injury, whereas loss of both YAP and TAZ in podocytes rapidly compromises the filtration barrier. α3β1 and αvβ5 are two prominent integrins on murine podocytes. Podocyte injury or loss of α3β1 leads to increased abundance of αvβ5 and nuclear localization of YAP. In vitro, blockade of αvβ5 decreases nuclear YAP. Increased αv integrins are found in human kidney disease. Thus, our studies demonstrate the crucial regulatory interplay between cell adhesion and transcriptional regulation as an important determinant of human disease. |
| format | Article |
| id | doaj-art-92b32e74f7ca48b19db1e8a1921bd4a0 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-92b32e74f7ca48b19db1e8a1921bd4a02025-08-20T02:17:10ZengNature PortfolioNature Communications2041-17232025-04-0116111710.1038/s41467-025-58567-yThe integrin repertoire drives YAP-dependent epithelial:stromal interactions during injury of the kidney glomerulusEvelyne Huynh-Cong0Victoria Driscoll1Sandrine Ettou2Keith Keller3Amha Atakilit4Mary E. Taglienti5Saurabh Kumar6Astrid Weins7Valerie A. Schumacher8Jordan A. Kreidberg9Department of Urology, Boston Children’s HospitalDivision of Nephrology, Beth Israel Deaconess Medical CenterDepartment of Urology, Boston Children’s HospitalDepartment of Pathology, Brigham and Women’s Hospital and Harvard Medical SchoolLung Biology Center, Department of Medicine, University of California San FranciscoDepartment of Urology, Boston Children’s HospitalDepartment of Urology, Boston Children’s HospitalDepartment of Pathology, Brigham and Women’s Hospital and Harvard Medical SchoolDepartment of Urology, Boston Children’s HospitalDepartment of Urology, Boston Children’s HospitalAbstract The kidney glomerulus is a filtration barrier in which capillary loop architecture depends on epithelial-stromal interactions between podocytes and mesangial cells. Podocytes are terminally differentiated cells within the glomerulus that express YAP and TAZ. Here we test the hypotheses that YAP and TAZ are required in podocytes to maintain capillary loop architecture and that shifts in the integrin repertoire during podocyte injury affect transcriptional activity of YAP and TAZ. Loss of YAP in podocytes of adult mice renders them more sensitive to injury, whereas loss of both YAP and TAZ in podocytes rapidly compromises the filtration barrier. α3β1 and αvβ5 are two prominent integrins on murine podocytes. Podocyte injury or loss of α3β1 leads to increased abundance of αvβ5 and nuclear localization of YAP. In vitro, blockade of αvβ5 decreases nuclear YAP. Increased αv integrins are found in human kidney disease. Thus, our studies demonstrate the crucial regulatory interplay between cell adhesion and transcriptional regulation as an important determinant of human disease.https://doi.org/10.1038/s41467-025-58567-y |
| spellingShingle | Evelyne Huynh-Cong Victoria Driscoll Sandrine Ettou Keith Keller Amha Atakilit Mary E. Taglienti Saurabh Kumar Astrid Weins Valerie A. Schumacher Jordan A. Kreidberg The integrin repertoire drives YAP-dependent epithelial:stromal interactions during injury of the kidney glomerulus Nature Communications |
| title | The integrin repertoire drives YAP-dependent epithelial:stromal interactions during injury of the kidney glomerulus |
| title_full | The integrin repertoire drives YAP-dependent epithelial:stromal interactions during injury of the kidney glomerulus |
| title_fullStr | The integrin repertoire drives YAP-dependent epithelial:stromal interactions during injury of the kidney glomerulus |
| title_full_unstemmed | The integrin repertoire drives YAP-dependent epithelial:stromal interactions during injury of the kidney glomerulus |
| title_short | The integrin repertoire drives YAP-dependent epithelial:stromal interactions during injury of the kidney glomerulus |
| title_sort | integrin repertoire drives yap dependent epithelial stromal interactions during injury of the kidney glomerulus |
| url | https://doi.org/10.1038/s41467-025-58567-y |
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