Bibliographic Details
| Title: |
Lsm2 is critical to club cell proliferation and its inhibition aggravates COPD progression |
| Authors: |
Wensi Zhu, Linxiao Han, Ludan He, Wenjun Peng, Ying Li, Weibin Tian, Hui Qi, Shuoyan Wei, Jie Shen, Yuanlin Song, Yao Shen, Qiaoliang Zhu, Jian Zhou |
| Source: |
Respiratory Research, Vol 26, Iss 1, Pp 1-18 (2025) |
| Publisher Information: |
BMC, 2025. |
| Publication Year: |
2025 |
| Collection: |
LCC:Diseases of the respiratory system |
| Subject Terms: |
Lsm2, COPD, Club cells, Ciliated epithelial cells, Diseases of the respiratory system, RC705-779 |
| More Details: |
Abstract Background Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory condition, with its severity inversely related to the levels of Club cell 10 kDa secretory protein (CC10). The gene Lsm2, involved in RNA metabolism and cell proliferation, has an unclear role in COPD development. Methods An in vitro COPD model was developed by stimulating 16HBE cells with cigarette smoke extract (CSE). To establish an in vivo COPD model, mice with defective Lsm2 gene expression in lung or club cells were exposed to cigarette smoke for 3 months. Multiplexed immunohistochemistry (mIHC) was employed to identify the specific cells where Lsm2 gene expression is predominant. RNA sequencing and single-nucleus RNA sequencing were conducted to investigate the role of Lsm2 in the pathogenesis of COPD. Results In this study, we found that cigarette smoke extract increases Lsm2 expression, and knocking down Lsm2 in 16HBE cells significantly reduces cell viability in vitro. mIHC showed that Lsm2 is primarily expressed in Club cells. Knockout of Lsm2, either in the lungs or specifically in Club cells, exacerbated lung injury and inflammation caused by cigarette smoke exposure in vivo. Single-nucleus RNA sequencing analysis revealed that Club cell-specific knockout of Lsm2 leads to a reduction in the Club cell population, particularly those expressing Chia1+/Crb1+. This decrease in Club cells subsequently reduces the number of ciliated epithelial cells. Conclusion Knocking out Lsm2 in Club cells results in a significant decrease in Club cell numbers, which subsequently leads to a reduction in ciliated epithelial cells. This increased lung vulnerability to cigarette smoke and accelerating the progression of COPD. Our findings highlight that Lsm2 is critical to club cell proliferation and its inhibition aggravates COPD progression. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1465-993X |
| Relation: |
https://doaj.org/toc/1465-993X |
| DOI: |
10.1186/s12931-025-03126-8 |
| Access URL: |
https://doaj.org/article/fe83ad292742468185aba193b509a1da |
| Accession Number: |
edsdoj.fe83ad292742468185aba193b509a1da |
| Database: |
Directory of Open Access Journals |
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