Niche-Dependent Regulation of Lkb1 in the Proliferation of Lung Epithelial Progenitor Cells
Lung homeostasis and regeneration depend on lung epithelial progenitor cells. <i>Lkb1</i> (Liver Kinase B1) has known roles in the differentiation of airway epithelial cells during embryonic development. However, the effects of <i>Lkb1</i> in adult lung epithelial progenitor...
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/23/15065 |
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| author | Qingwen Ma Xue Li Sisi Wang Qi Wang Yu Li Kuan Li Jianhai Wang Qiuyang Zhang Junping Wu Huaiyong Chen |
| author_facet | Qingwen Ma Xue Li Sisi Wang Qi Wang Yu Li Kuan Li Jianhai Wang Qiuyang Zhang Junping Wu Huaiyong Chen |
| author_sort | Qingwen Ma |
| collection | DOAJ |
| description | Lung homeostasis and regeneration depend on lung epithelial progenitor cells. <i>Lkb1</i> (Liver Kinase B1) has known roles in the differentiation of airway epithelial cells during embryonic development. However, the effects of <i>Lkb1</i> in adult lung epithelial progenitor cell regeneration and its mechanisms of action have not been determined. In this study, we investigated the mechanism by which <i>Lkb1</i> regulates lung epithelial progenitor cell regeneration. Organoid culture showed that loss of <i>Lkb1</i> significantly reduced the proliferation of club cells and alveolar type 2 (AT2) cells in vitro. In the absence of <i>Lkb1</i>, there is a slower recovery rate of the damaged airway epithelium in naphthalene-induced airway epithelial injury and impaired expression of surfactant protein C during bleomycin-induced alveolar epithelial damage. Moreover, the expression of autophagy-related genes was reduced in club cells and increased in AT2 cells, but the expression of <i>Claudin-18</i> was obviously reduced in AT2 cells after <i>Lkb1</i> knockdown. On the whole, our findings indicated that <i>Lkb1</i> may promote the proliferation of lung epithelial progenitor cells via a niche-dependent pathway and is required for the repair of the damaged lung epithelium. |
| first_indexed | 2024-03-09T17:45:30Z |
| format | Article |
| id | doaj.art-7049371ffee44fb6b70ad0fe3cdb2f8a |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T17:45:30Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-7049371ffee44fb6b70ad0fe3cdb2f8a2023-11-24T11:12:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123231506510.3390/ijms232315065Niche-Dependent Regulation of Lkb1 in the Proliferation of Lung Epithelial Progenitor CellsQingwen Ma0Xue Li1Sisi Wang2Qi Wang3Yu Li4Kuan Li5Jianhai Wang6Qiuyang Zhang7Junping Wu8Huaiyong Chen9Department of Basic Medicine, Haihe Clinical School, Tianjin Medical University, Jinnan District, Tianjin 300350, ChinaDepartment of Basic Medicine, Haihe Clinical School, Tianjin Medical University, Jinnan District, Tianjin 300350, ChinaDepartment of Basic Medicine, Haihe Clinical School, Tianjin Medical University, Jinnan District, Tianjin 300350, ChinaDepartment of Basic Medicine, Haihe Hospital, Tianjin University, Jinan District, Tianjin 300350, ChinaDepartment of Basic Medicine, Haihe Hospital, Tianjin University, Jinan District, Tianjin 300350, ChinaDepartment of Basic Medicine, Haihe Hospital, Tianjin University, Jinan District, Tianjin 300350, ChinaDepartment of Basic Medicine, Haihe Hospital, Tianjin University, Jinan District, Tianjin 300350, ChinaDepartment of Basic Medicine, Haihe Hospital, Tianjin University, Jinan District, Tianjin 300350, ChinaDepartment of Tuberculosis, Haihe Hospital, Tianjin University, Jinnan District, Tianjin 300350, ChinaDepartment of Basic Medicine, Haihe Clinical School, Tianjin Medical University, Jinnan District, Tianjin 300350, ChinaLung homeostasis and regeneration depend on lung epithelial progenitor cells. <i>Lkb1</i> (Liver Kinase B1) has known roles in the differentiation of airway epithelial cells during embryonic development. However, the effects of <i>Lkb1</i> in adult lung epithelial progenitor cell regeneration and its mechanisms of action have not been determined. In this study, we investigated the mechanism by which <i>Lkb1</i> regulates lung epithelial progenitor cell regeneration. Organoid culture showed that loss of <i>Lkb1</i> significantly reduced the proliferation of club cells and alveolar type 2 (AT2) cells in vitro. In the absence of <i>Lkb1</i>, there is a slower recovery rate of the damaged airway epithelium in naphthalene-induced airway epithelial injury and impaired expression of surfactant protein C during bleomycin-induced alveolar epithelial damage. Moreover, the expression of autophagy-related genes was reduced in club cells and increased in AT2 cells, but the expression of <i>Claudin-18</i> was obviously reduced in AT2 cells after <i>Lkb1</i> knockdown. On the whole, our findings indicated that <i>Lkb1</i> may promote the proliferation of lung epithelial progenitor cells via a niche-dependent pathway and is required for the repair of the damaged lung epithelium.https://www.mdpi.com/1422-0067/23/23/15065<i>Lkb1</i>lung epithelial progenitor cellsproliferationrepairautophagy<i>Claudin-18</i> |
| spellingShingle | Qingwen Ma Xue Li Sisi Wang Qi Wang Yu Li Kuan Li Jianhai Wang Qiuyang Zhang Junping Wu Huaiyong Chen Niche-Dependent Regulation of Lkb1 in the Proliferation of Lung Epithelial Progenitor Cells International Journal of Molecular Sciences <i>Lkb1</i> lung epithelial progenitor cells proliferation repair autophagy <i>Claudin-18</i> |
| title | Niche-Dependent Regulation of Lkb1 in the Proliferation of Lung Epithelial Progenitor Cells |
| title_full | Niche-Dependent Regulation of Lkb1 in the Proliferation of Lung Epithelial Progenitor Cells |
| title_fullStr | Niche-Dependent Regulation of Lkb1 in the Proliferation of Lung Epithelial Progenitor Cells |
| title_full_unstemmed | Niche-Dependent Regulation of Lkb1 in the Proliferation of Lung Epithelial Progenitor Cells |
| title_short | Niche-Dependent Regulation of Lkb1 in the Proliferation of Lung Epithelial Progenitor Cells |
| title_sort | niche dependent regulation of lkb1 in the proliferation of lung epithelial progenitor cells |
| topic | <i>Lkb1</i> lung epithelial progenitor cells proliferation repair autophagy <i>Claudin-18</i> |
| url | https://www.mdpi.com/1422-0067/23/23/15065 |
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