Abstract
Gasdermin (GSDM) family, the key executioners of pyroptosis, play crucial roles in anti-pathogen and anti-tumor immunities, although little is known about the expression of GSDM in lung diseases at single-cell resolution, especially in lung epithelial cells. We comprehensively investigated the transcriptomic profiles of GSDM members in various lung tissues from healthy subjects or patients with different lung diseases at single cell level, e.g., chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), lung adenocarcinoma (LUAD), or systemic sclerosis (SSC). The expression of GSDM members varied among pulmonary cell types (immune cells, structural cells, and especially epithelial cells) and even across lung diseases. Regarding disease-associated specificities, we found that GSDMC or GSDMD altered significantly in ciliated epithelia of COPD or LUAD, GSDMD in mucous, club, and basal cells of LUAD and GSDMC in mucous epithelia of para-tumor tissue, as compared with the corresponding epithelia of other diseases. The phenomic specificity of GSDM in lung cancer subtypes was noticed by comparing with 15 non-pulmonary cancers and para-cancer samples. GSDM family gene expression changes were also observed in different lung epithelial cell lines (e.g., HBE, A549, H1299, SPC-1, or H460) in responses to external challenges, including lipopolysaccharide (LPS), lysophosphatidylcholine (lysoPC), cigarette smoking extract (CSE), cholesterol, and AR2 inhibitor at various doses or durations. GSDMA is rarely expressed in those cell lines, while GSDMB and GSDMC are significantly upregulated in human lung epithelia. Our data indicated that the heterogeneity of GSDM member expression exists at different cells, pathologic conditions, challenges, probably dependent upon cell biological phenomes, functions, and behaviors, upon cellular responses to external changes, and the nature and severity of lung disease. Thus, the deep exploration of GSDM phenomes may provide new insights into understanding the single-cell roles in the tissue, regulatory roles of the GSDM family in the pathogenesis, and potential values of biomarker identification and development.
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Abbreviations
- COPD :
-
Chronic obstructive pulmonary disease
- IPF :
-
Idiopathic pulmonary fibrosis
- SSC :
-
Systemic sclerosis
- LUAD :
-
Lung adenocarcinoma
- GSDM :
-
Gasdermin
- GSDMA :
-
Gasdermin A
- GSDMB :
-
Gasdermin B
- GSDMC :
-
Gasdermin C
- GSDMD:
-
Gasdermin D
- PJVK:
-
Pejvakin
- Normal :
-
Normal lung tissue
- LUAD :
-
Lung adenocarcinoma
- LUAD-P :
-
Para-adenocarcinoma lung tissue
- LUSC :
-
Lung squamous carcinoma
- LUSC-P :
-
Para-squamous carcinoma lung tissue
- GBM :
-
Glioblastoma multiforme
- BLCA :
-
Bladder urothelial carcinoma
- BRCA :
-
Breast invasive carcinoma
- CHOL :
-
Cholangiocarcinoma
- ESCA :
-
Esophageal carcinoma
- KIRP :
-
Kidney renal papillary cell carcinoma
- LIHC :
-
Liver hepatocellular carcinoma
- PRAD :
-
Prostate adenocarcinoma
- STAD :
-
Stomach adenocarcinoma
- THCA :
-
Thyroid carcinoma
- COAD :
-
Colon adenocarcinoma
- AR2 :
-
Androgen receptor2
- HBE :
-
Human bronchial epithelial cell
- PCD :
-
Programmed cell death
- LPS :
-
Lipopolysaccharide
- LysoPC :
-
Lysophosphatidylcholine
- CSE :
-
Cigarette smoking extract
- LS :
-
Lung surfactants
- PLCG1 :
-
Phospholipase C gamma 1
- GPC :
-
G protein-coupled receptor (GPC)
- TLR :
-
Toll-like receptor
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National Nature Science Foundation of China (81873409), “Cross key project of mathematics and medical health” of National Natural Science Foundation of China (12026608), and partly supported by Pazhou Lab.
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Xiangdong Wang, Ajay Goel, Chengshui Chen, and Yiming Zeng contributed to the study conception and design. Xuanqi Liu, Linlin Zhang, Bijun Zhu, Yifei Liu, Liyang Li, Jiayun Hou, Mengjia Qian, and Nannan Zheng analyzed the data and finished the manuscript writing. All authors contributed to the writing and reviewing of the manuscript and approved the final manuscript for submission.
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Highlights
1. Transcriptomic atlas of GSDM family members vary across diverse lung epithelial cells, lung diseases and external stimuli.
2. GSDM family members play crucial roles in pyroptosis, one of the programmed cell death in lung diseases.
3. GSDM family genes are potentially valuable as the biomarkers and therapeutic targets in lung diseases.
Linlin Zhang, Bijun Zhu, Yifei Liu, Jiayun Hou, Mengjia Qian, Nannan Zheng, and Yiming Zeng contributed to this work equally as the first author.
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Liu, X., Zhang, L., Zhu, B. et al. Role of GSDM family members in airway epithelial cells of lung diseases: a systematic and comprehensive transcriptomic analysis. Cell Biol Toxicol 39, 2743–2760 (2023). https://doi.org/10.1007/s10565-023-09799-5
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DOI: https://doi.org/10.1007/s10565-023-09799-5