Aging of alveolar type 2 cells induced by Lonp1 deficiency exacerbates pulmonary fibrosis
Idiopathic pulmonary fibrosis (IPF) is a progressive and chronic disease that significantly impacts patient quality of life, and its incidence is on the rise. The pathogenesis of IPF remains poorly understood. Alveolar type 2 (AT2) cells are crucial in the onset and progression of IPF, yet the spec...
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| Format: | Article |
| Language: | English |
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Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina
2024-04-01
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| Series: | Biomolecules & Biomedicine |
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| Online Access: | https://www.bjbms.org/ojs/index.php/bjbms/article/view/10429 |
| _version_ | 1797202408160362496 |
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| author | Weiwei Zhu Chunting Tan Jie Zhang |
| author_facet | Weiwei Zhu Chunting Tan Jie Zhang |
| author_sort | Weiwei Zhu |
| collection | DOAJ |
| description |
Idiopathic pulmonary fibrosis (IPF) is a progressive and chronic disease that significantly impacts patient quality of life, and its incidence is on the rise. The pathogenesis of IPF remains poorly understood. Alveolar type 2 (AT2) cells are crucial in the onset and progression of IPF, yet the specific mechanisms involved are not well defined. Lon protease 1 (LONP1), known for its critical roles in various diseases, has an unclear function in IPF. Our research investigated the impact of Lonp1 gene deletion on AT2 cell functionality and its subsequent effect on IPF development. We generated a bleomycin-induced pulmonary fibrosis mouse model with a targeted Lonp1 knockout in AT2 cells and assessed the consequences on AT2 cell function and fibrosis progression. Additionally, we constructed the MLE12 cells with stable Lonp1 knockdown and utilized transcriptome sequencing to identify pathways altered by the Lonp1 knockdown. Our results indicated that mice with AT2 cell-specific Lonp1 knockout exhibited more severe fibrosis compared to controls. These mice exhibited a reduction in AT2 and AT1 cell populations, along with an increase in p53- and p21-positive AT2 cells. Lonp1 knockdown in MLE12 cells led to the upregulation of aging-associated pathways, with fibroblast growth factor 2 (Fgf2) gene emerging as a central gene interconnecting these pathways. Therefore, loss of Lonp1 appears to promote AT2 cell aging and exacerbate bleomycin-induced pulmonary fibrosis. Fgf2 emerges as a pivotal downstream gene associated with cellular senescence. This study uncovers the role of the Lonp1 gene in pulmonary fibrosis, presenting a novel target for investigating the pathological mechanisms and potential therapeutic approaches for IPF.
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| first_indexed | 2024-04-24T08:02:58Z |
| format | Article |
| id | doaj.art-9800a6fc4d6b4827abfcdc137db55e63 |
| institution | Directory Open Access Journal |
| issn | 2831-0896 2831-090X |
| language | English |
| last_indexed | 2024-04-24T08:02:58Z |
| publishDate | 2024-04-01 |
| publisher | Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina |
| record_format | Article |
| series | Biomolecules & Biomedicine |
| spelling | doaj.art-9800a6fc4d6b4827abfcdc137db55e632024-04-17T14:50:24ZengAssociation of Basic Medical Sciences of Federation of Bosnia and HerzegovinaBiomolecules & Biomedicine2831-08962831-090X2024-04-0110.17305/bb.2024.10429Aging of alveolar type 2 cells induced by Lonp1 deficiency exacerbates pulmonary fibrosisWeiwei Zhu0Chunting Tan1Jie Zhang2Department of Pulmonary and Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaDepartment of Pulmonary and Critical Care Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, ChinaDepartment of Pulmonary and Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China Idiopathic pulmonary fibrosis (IPF) is a progressive and chronic disease that significantly impacts patient quality of life, and its incidence is on the rise. The pathogenesis of IPF remains poorly understood. Alveolar type 2 (AT2) cells are crucial in the onset and progression of IPF, yet the specific mechanisms involved are not well defined. Lon protease 1 (LONP1), known for its critical roles in various diseases, has an unclear function in IPF. Our research investigated the impact of Lonp1 gene deletion on AT2 cell functionality and its subsequent effect on IPF development. We generated a bleomycin-induced pulmonary fibrosis mouse model with a targeted Lonp1 knockout in AT2 cells and assessed the consequences on AT2 cell function and fibrosis progression. Additionally, we constructed the MLE12 cells with stable Lonp1 knockdown and utilized transcriptome sequencing to identify pathways altered by the Lonp1 knockdown. Our results indicated that mice with AT2 cell-specific Lonp1 knockout exhibited more severe fibrosis compared to controls. These mice exhibited a reduction in AT2 and AT1 cell populations, along with an increase in p53- and p21-positive AT2 cells. Lonp1 knockdown in MLE12 cells led to the upregulation of aging-associated pathways, with fibroblast growth factor 2 (Fgf2) gene emerging as a central gene interconnecting these pathways. Therefore, loss of Lonp1 appears to promote AT2 cell aging and exacerbate bleomycin-induced pulmonary fibrosis. Fgf2 emerges as a pivotal downstream gene associated with cellular senescence. This study uncovers the role of the Lonp1 gene in pulmonary fibrosis, presenting a novel target for investigating the pathological mechanisms and potential therapeutic approaches for IPF. https://www.bjbms.org/ojs/index.php/bjbms/article/view/10429Idiopathic pulmonary fibrosis (IPF)Lon protease 1 (Lonp1) genesenescence |
| spellingShingle | Weiwei Zhu Chunting Tan Jie Zhang Aging of alveolar type 2 cells induced by Lonp1 deficiency exacerbates pulmonary fibrosis Biomolecules & Biomedicine Idiopathic pulmonary fibrosis (IPF) Lon protease 1 (Lonp1) gene senescence |
| title | Aging of alveolar type 2 cells induced by Lonp1 deficiency exacerbates pulmonary fibrosis |
| title_full | Aging of alveolar type 2 cells induced by Lonp1 deficiency exacerbates pulmonary fibrosis |
| title_fullStr | Aging of alveolar type 2 cells induced by Lonp1 deficiency exacerbates pulmonary fibrosis |
| title_full_unstemmed | Aging of alveolar type 2 cells induced by Lonp1 deficiency exacerbates pulmonary fibrosis |
| title_short | Aging of alveolar type 2 cells induced by Lonp1 deficiency exacerbates pulmonary fibrosis |
| title_sort | aging of alveolar type 2 cells induced by lonp1 deficiency exacerbates pulmonary fibrosis |
| topic | Idiopathic pulmonary fibrosis (IPF) Lon protease 1 (Lonp1) gene senescence |
| url | https://www.bjbms.org/ojs/index.php/bjbms/article/view/10429 |
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