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KLF11 deficiency enhances chemokine generation and fibrosis in murine unilateral ureteral obstruction
Progression of virtually all forms of chronic kidney disease (CKD) is associated with activation of pro-inflammatory and pro-fibrotic signaling pathways. Despite extensive research, progress in identifying therapeutic targets to arrest or slow progression of CKD has been limited by incomplete unders...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9004740/ https://www.ncbi.nlm.nih.gov/pubmed/35413089 http://dx.doi.org/10.1371/journal.pone.0266454 |
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author | De Lorenzo, Silvana B. Vrieze, Alyssa M. Johnson, Ruth A. Lien, Karen R. Nath, Karl A. Garovic, Vesna D. Khazaie, Khashayarsha Grande, Joseph P. |
author_facet | De Lorenzo, Silvana B. Vrieze, Alyssa M. Johnson, Ruth A. Lien, Karen R. Nath, Karl A. Garovic, Vesna D. Khazaie, Khashayarsha Grande, Joseph P. |
author_sort | De Lorenzo, Silvana B. |
collection | PubMed |
description | Progression of virtually all forms of chronic kidney disease (CKD) is associated with activation of pro-inflammatory and pro-fibrotic signaling pathways. Despite extensive research, progress in identifying therapeutic targets to arrest or slow progression of CKD has been limited by incomplete understanding of basic mechanisms underlying renal inflammation and fibrosis in CKD. Recent studies have identified Kruppel-like transcription factors that have been shown to play critical roles in renal development, homeostasis, and response to injury. Although KLF11 deficiency has been shown to increase collagen production in vitro and tissue fibrosis in other organs, no previous study has linked KLF11 to the development of CKD. We sought to test the hypothesis that KLF11 deficiency promotes CKD through upregulation of pro-inflammatory and pro-fibrogenic signaling pathways in murine unilateral ureteral obstruction (UUO), a well-established model of renal fibrosis. We found that KLF11-deficiency exacerbates renal injury in the UUO model through activation of the TGF-β/SMAD signaling pathway and through activation of several pro-inflammatory chemokine signaling pathways. Based on these considerations, we conclude that agents increase KLF11 expression may provide novel therapeutic targets to slow the progression of CKD. |
format | Online Article Text |
id | pubmed-9004740 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-90047402022-04-13 KLF11 deficiency enhances chemokine generation and fibrosis in murine unilateral ureteral obstruction De Lorenzo, Silvana B. Vrieze, Alyssa M. Johnson, Ruth A. Lien, Karen R. Nath, Karl A. Garovic, Vesna D. Khazaie, Khashayarsha Grande, Joseph P. PLoS One Research Article Progression of virtually all forms of chronic kidney disease (CKD) is associated with activation of pro-inflammatory and pro-fibrotic signaling pathways. Despite extensive research, progress in identifying therapeutic targets to arrest or slow progression of CKD has been limited by incomplete understanding of basic mechanisms underlying renal inflammation and fibrosis in CKD. Recent studies have identified Kruppel-like transcription factors that have been shown to play critical roles in renal development, homeostasis, and response to injury. Although KLF11 deficiency has been shown to increase collagen production in vitro and tissue fibrosis in other organs, no previous study has linked KLF11 to the development of CKD. We sought to test the hypothesis that KLF11 deficiency promotes CKD through upregulation of pro-inflammatory and pro-fibrogenic signaling pathways in murine unilateral ureteral obstruction (UUO), a well-established model of renal fibrosis. We found that KLF11-deficiency exacerbates renal injury in the UUO model through activation of the TGF-β/SMAD signaling pathway and through activation of several pro-inflammatory chemokine signaling pathways. Based on these considerations, we conclude that agents increase KLF11 expression may provide novel therapeutic targets to slow the progression of CKD. Public Library of Science 2022-04-12 /pmc/articles/PMC9004740/ /pubmed/35413089 http://dx.doi.org/10.1371/journal.pone.0266454 Text en © 2022 De Lorenzo et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article De Lorenzo, Silvana B. Vrieze, Alyssa M. Johnson, Ruth A. Lien, Karen R. Nath, Karl A. Garovic, Vesna D. Khazaie, Khashayarsha Grande, Joseph P. KLF11 deficiency enhances chemokine generation and fibrosis in murine unilateral ureteral obstruction |
title | KLF11 deficiency enhances chemokine generation and fibrosis in murine unilateral ureteral obstruction |
title_full | KLF11 deficiency enhances chemokine generation and fibrosis in murine unilateral ureteral obstruction |
title_fullStr | KLF11 deficiency enhances chemokine generation and fibrosis in murine unilateral ureteral obstruction |
title_full_unstemmed | KLF11 deficiency enhances chemokine generation and fibrosis in murine unilateral ureteral obstruction |
title_short | KLF11 deficiency enhances chemokine generation and fibrosis in murine unilateral ureteral obstruction |
title_sort | klf11 deficiency enhances chemokine generation and fibrosis in murine unilateral ureteral obstruction |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9004740/ https://www.ncbi.nlm.nih.gov/pubmed/35413089 http://dx.doi.org/10.1371/journal.pone.0266454 |
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