Cargando…
Canonical NF-κB signaling maintains corneal epithelial integrity and prevents corneal aging via retinoic acid
Disorders of the transparent cornea affect millions of people worldwide. However, how to maintain and/or regenerate this organ remains unclear. Here, we show that Rela (encoding a canonical NF-κB subunit) ablation in K14(+) corneal epithelial stem cells not only disrupts corneal regeneration but als...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192125/ https://www.ncbi.nlm.nih.gov/pubmed/34085926 http://dx.doi.org/10.7554/eLife.67315 |
_version_ | 1783705991539326976 |
---|---|
author | Yu, Qian Biswas, Soma Ma, Gang Zhao, Peiquan Li, Baojie Li, Jing |
author_facet | Yu, Qian Biswas, Soma Ma, Gang Zhao, Peiquan Li, Baojie Li, Jing |
author_sort | Yu, Qian |
collection | PubMed |
description | Disorders of the transparent cornea affect millions of people worldwide. However, how to maintain and/or regenerate this organ remains unclear. Here, we show that Rela (encoding a canonical NF-κB subunit) ablation in K14(+) corneal epithelial stem cells not only disrupts corneal regeneration but also results in age-dependent epithelial deterioration, which triggers aberrant wound-healing processes including stromal remodeling, neovascularization, epithelial metaplasia, and plaque formation at the central cornea. These anomalies are largely recapitulated in normal mice that age naturally. Mechanistically, Rela deletion suppresses expression of Aldh1a1, an enzyme required for retinoic acid synthesis from vitamin A. Retinoic acid administration blocks development of ocular anomalies in Krt14-Cre; Rela(f/f) mice and naturally aged mice. Moreover, epithelial metaplasia and plaque formation are preventable by inhibition of angiogenesis. This study thus uncovers the major mechanisms governing corneal maintenance, regeneration, and aging and identifies the NF-κB-retinoic acid pathway as a therapeutic target for corneal disorders. |
format | Online Article Text |
id | pubmed-8192125 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-81921252021-06-14 Canonical NF-κB signaling maintains corneal epithelial integrity and prevents corneal aging via retinoic acid Yu, Qian Biswas, Soma Ma, Gang Zhao, Peiquan Li, Baojie Li, Jing eLife Cell Biology Disorders of the transparent cornea affect millions of people worldwide. However, how to maintain and/or regenerate this organ remains unclear. Here, we show that Rela (encoding a canonical NF-κB subunit) ablation in K14(+) corneal epithelial stem cells not only disrupts corneal regeneration but also results in age-dependent epithelial deterioration, which triggers aberrant wound-healing processes including stromal remodeling, neovascularization, epithelial metaplasia, and plaque formation at the central cornea. These anomalies are largely recapitulated in normal mice that age naturally. Mechanistically, Rela deletion suppresses expression of Aldh1a1, an enzyme required for retinoic acid synthesis from vitamin A. Retinoic acid administration blocks development of ocular anomalies in Krt14-Cre; Rela(f/f) mice and naturally aged mice. Moreover, epithelial metaplasia and plaque formation are preventable by inhibition of angiogenesis. This study thus uncovers the major mechanisms governing corneal maintenance, regeneration, and aging and identifies the NF-κB-retinoic acid pathway as a therapeutic target for corneal disorders. eLife Sciences Publications, Ltd 2021-06-04 /pmc/articles/PMC8192125/ /pubmed/34085926 http://dx.doi.org/10.7554/eLife.67315 Text en © 2021, Yu et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Cell Biology Yu, Qian Biswas, Soma Ma, Gang Zhao, Peiquan Li, Baojie Li, Jing Canonical NF-κB signaling maintains corneal epithelial integrity and prevents corneal aging via retinoic acid |
title | Canonical NF-κB signaling maintains corneal epithelial integrity and prevents corneal aging via retinoic acid |
title_full | Canonical NF-κB signaling maintains corneal epithelial integrity and prevents corneal aging via retinoic acid |
title_fullStr | Canonical NF-κB signaling maintains corneal epithelial integrity and prevents corneal aging via retinoic acid |
title_full_unstemmed | Canonical NF-κB signaling maintains corneal epithelial integrity and prevents corneal aging via retinoic acid |
title_short | Canonical NF-κB signaling maintains corneal epithelial integrity and prevents corneal aging via retinoic acid |
title_sort | canonical nf-κb signaling maintains corneal epithelial integrity and prevents corneal aging via retinoic acid |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192125/ https://www.ncbi.nlm.nih.gov/pubmed/34085926 http://dx.doi.org/10.7554/eLife.67315 |
work_keys_str_mv | AT yuqian canonicalnfkbsignalingmaintainscornealepithelialintegrityandpreventscornealagingviaretinoicacid AT biswassoma canonicalnfkbsignalingmaintainscornealepithelialintegrityandpreventscornealagingviaretinoicacid AT magang canonicalnfkbsignalingmaintainscornealepithelialintegrityandpreventscornealagingviaretinoicacid AT zhaopeiquan canonicalnfkbsignalingmaintainscornealepithelialintegrityandpreventscornealagingviaretinoicacid AT libaojie canonicalnfkbsignalingmaintainscornealepithelialintegrityandpreventscornealagingviaretinoicacid AT lijing canonicalnfkbsignalingmaintainscornealepithelialintegrityandpreventscornealagingviaretinoicacid |