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Krüppel-like factor 5 regulates wound repair and the innate immune response in human airway epithelial cells
A complex network of transcription factors regulates genes involved in establishing and maintaining key biological properties of the human airway epithelium. However, detailed knowledge of the contributing factors is incomplete. Here we characterize the role of Krüppel-like factor 5 (KLF5), in contr...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353497/ https://www.ncbi.nlm.nih.gov/pubmed/34217701 http://dx.doi.org/10.1016/j.jbc.2021.100932 |
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author | Paranjapye, Alekh NandyMazumdar, Monali Browne, James A. Leir, Shih-Hsing Harris, Ann |
author_facet | Paranjapye, Alekh NandyMazumdar, Monali Browne, James A. Leir, Shih-Hsing Harris, Ann |
author_sort | Paranjapye, Alekh |
collection | PubMed |
description | A complex network of transcription factors regulates genes involved in establishing and maintaining key biological properties of the human airway epithelium. However, detailed knowledge of the contributing factors is incomplete. Here we characterize the role of Krüppel-like factor 5 (KLF5), in controlling essential pathways of epithelial cell identity and function in the human lung. RNA-seq following siRNA-mediated depletion of KLF5 in the Calu-3 lung epithelial cell line identified significant enrichment of genes encoding chemokines and cytokines involved in the proinflammatory response and also components of the junctional complexes mediating cell adhesion. To determine direct gene targets of KLF5, we defined the cistrome of KLF5 using ChIP-seq in both Calu-3 and 16HBE14o(−) lung epithelial cell lines. Occupancy site concordance analysis revealed that KLF5 colocalized with the active histone modification H3K27ac and also with binding sites for the transcription factor CCAAT enhancer-binding protein beta (C/EBPβ). Depletion of KLF5 increased both the expression and secretion of cytokines including IL-1β, a response that was enhanced following exposure to Pseudomonas aeruginosa lipopolysaccharide. Calu-3 cells exhibited faster rates of repair after KLF5 depletion compared with negative controls in wound scratch assays. Similarly, CRISPR-mediated KLF5-null 16HBE14o(−) cells also showed enhanced wound closure. These data reveal a pivotal role for KLF5 in coordinating epithelial functions relevant to human lung disease. |
format | Online Article Text |
id | pubmed-8353497 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-83534972021-08-15 Krüppel-like factor 5 regulates wound repair and the innate immune response in human airway epithelial cells Paranjapye, Alekh NandyMazumdar, Monali Browne, James A. Leir, Shih-Hsing Harris, Ann J Biol Chem Research Article A complex network of transcription factors regulates genes involved in establishing and maintaining key biological properties of the human airway epithelium. However, detailed knowledge of the contributing factors is incomplete. Here we characterize the role of Krüppel-like factor 5 (KLF5), in controlling essential pathways of epithelial cell identity and function in the human lung. RNA-seq following siRNA-mediated depletion of KLF5 in the Calu-3 lung epithelial cell line identified significant enrichment of genes encoding chemokines and cytokines involved in the proinflammatory response and also components of the junctional complexes mediating cell adhesion. To determine direct gene targets of KLF5, we defined the cistrome of KLF5 using ChIP-seq in both Calu-3 and 16HBE14o(−) lung epithelial cell lines. Occupancy site concordance analysis revealed that KLF5 colocalized with the active histone modification H3K27ac and also with binding sites for the transcription factor CCAAT enhancer-binding protein beta (C/EBPβ). Depletion of KLF5 increased both the expression and secretion of cytokines including IL-1β, a response that was enhanced following exposure to Pseudomonas aeruginosa lipopolysaccharide. Calu-3 cells exhibited faster rates of repair after KLF5 depletion compared with negative controls in wound scratch assays. Similarly, CRISPR-mediated KLF5-null 16HBE14o(−) cells also showed enhanced wound closure. These data reveal a pivotal role for KLF5 in coordinating epithelial functions relevant to human lung disease. American Society for Biochemistry and Molecular Biology 2021-07-01 /pmc/articles/PMC8353497/ /pubmed/34217701 http://dx.doi.org/10.1016/j.jbc.2021.100932 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Article Paranjapye, Alekh NandyMazumdar, Monali Browne, James A. Leir, Shih-Hsing Harris, Ann Krüppel-like factor 5 regulates wound repair and the innate immune response in human airway epithelial cells |
title | Krüppel-like factor 5 regulates wound repair and the innate immune response in human airway epithelial cells |
title_full | Krüppel-like factor 5 regulates wound repair and the innate immune response in human airway epithelial cells |
title_fullStr | Krüppel-like factor 5 regulates wound repair and the innate immune response in human airway epithelial cells |
title_full_unstemmed | Krüppel-like factor 5 regulates wound repair and the innate immune response in human airway epithelial cells |
title_short | Krüppel-like factor 5 regulates wound repair and the innate immune response in human airway epithelial cells |
title_sort | krüppel-like factor 5 regulates wound repair and the innate immune response in human airway epithelial cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353497/ https://www.ncbi.nlm.nih.gov/pubmed/34217701 http://dx.doi.org/10.1016/j.jbc.2021.100932 |
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