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ResearchIn-Press PreviewCell biologyInflammationPulmonology Open Access | 10.1172/JCI188822

Excessive collagen type VII mediates pleural fibrosis via increasing extracellular matrix stiffness

Qian Li,1 Xin-Liang He,2 Shuai-Jun Chen,1 Qian Niu,2 Tan-Ze Cao,3 Xiao-Ling Cui,1 Zi-Heng Jia,2 He-De Zhang,1 Xiao Feng,1 Ye-Han Jiang,2 Li-Mei Liang,2 Pei-Pei Cheng,1 Shi-He Hu,1 Liang Xiong,4 Meng Wang,1 Hong Ye,1 and Wan-Li Ma2

1Department of Pathophysiology, Huazhong University of Science and Technology, Wuhan, China

2Department of Respiratory and Critical Care Medicine, Huazhong University of Science and Technology, Wuhan, China

3Department of Respiratory and Critical Care Medicine, Wuhan Pulmonary Hospital, Wuhan, China

4Huazhong University of Science and Technology, Wuhan, China

Find articles by Li, Q. in: PubMed | Google Scholar

1Department of Pathophysiology, Huazhong University of Science and Technology, Wuhan, China

2Department of Respiratory and Critical Care Medicine, Huazhong University of Science and Technology, Wuhan, China

3Department of Respiratory and Critical Care Medicine, Wuhan Pulmonary Hospital, Wuhan, China

4Huazhong University of Science and Technology, Wuhan, China

Find articles by He, X. in: PubMed | Google Scholar

1Department of Pathophysiology, Huazhong University of Science and Technology, Wuhan, China

2Department of Respiratory and Critical Care Medicine, Huazhong University of Science and Technology, Wuhan, China

3Department of Respiratory and Critical Care Medicine, Wuhan Pulmonary Hospital, Wuhan, China

4Huazhong University of Science and Technology, Wuhan, China

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1Department of Pathophysiology, Huazhong University of Science and Technology, Wuhan, China

2Department of Respiratory and Critical Care Medicine, Huazhong University of Science and Technology, Wuhan, China

3Department of Respiratory and Critical Care Medicine, Wuhan Pulmonary Hospital, Wuhan, China

4Huazhong University of Science and Technology, Wuhan, China

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1Department of Pathophysiology, Huazhong University of Science and Technology, Wuhan, China

2Department of Respiratory and Critical Care Medicine, Huazhong University of Science and Technology, Wuhan, China

3Department of Respiratory and Critical Care Medicine, Wuhan Pulmonary Hospital, Wuhan, China

4Huazhong University of Science and Technology, Wuhan, China

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1Department of Pathophysiology, Huazhong University of Science and Technology, Wuhan, China

2Department of Respiratory and Critical Care Medicine, Huazhong University of Science and Technology, Wuhan, China

3Department of Respiratory and Critical Care Medicine, Wuhan Pulmonary Hospital, Wuhan, China

4Huazhong University of Science and Technology, Wuhan, China

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1Department of Pathophysiology, Huazhong University of Science and Technology, Wuhan, China

2Department of Respiratory and Critical Care Medicine, Huazhong University of Science and Technology, Wuhan, China

3Department of Respiratory and Critical Care Medicine, Wuhan Pulmonary Hospital, Wuhan, China

4Huazhong University of Science and Technology, Wuhan, China

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1Department of Pathophysiology, Huazhong University of Science and Technology, Wuhan, China

2Department of Respiratory and Critical Care Medicine, Huazhong University of Science and Technology, Wuhan, China

3Department of Respiratory and Critical Care Medicine, Wuhan Pulmonary Hospital, Wuhan, China

4Huazhong University of Science and Technology, Wuhan, China

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1Department of Pathophysiology, Huazhong University of Science and Technology, Wuhan, China

2Department of Respiratory and Critical Care Medicine, Huazhong University of Science and Technology, Wuhan, China

3Department of Respiratory and Critical Care Medicine, Wuhan Pulmonary Hospital, Wuhan, China

4Huazhong University of Science and Technology, Wuhan, China

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1Department of Pathophysiology, Huazhong University of Science and Technology, Wuhan, China

2Department of Respiratory and Critical Care Medicine, Huazhong University of Science and Technology, Wuhan, China

3Department of Respiratory and Critical Care Medicine, Wuhan Pulmonary Hospital, Wuhan, China

4Huazhong University of Science and Technology, Wuhan, China

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1Department of Pathophysiology, Huazhong University of Science and Technology, Wuhan, China

2Department of Respiratory and Critical Care Medicine, Huazhong University of Science and Technology, Wuhan, China

3Department of Respiratory and Critical Care Medicine, Wuhan Pulmonary Hospital, Wuhan, China

4Huazhong University of Science and Technology, Wuhan, China

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1Department of Pathophysiology, Huazhong University of Science and Technology, Wuhan, China

2Department of Respiratory and Critical Care Medicine, Huazhong University of Science and Technology, Wuhan, China

3Department of Respiratory and Critical Care Medicine, Wuhan Pulmonary Hospital, Wuhan, China

4Huazhong University of Science and Technology, Wuhan, China

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1Department of Pathophysiology, Huazhong University of Science and Technology, Wuhan, China

2Department of Respiratory and Critical Care Medicine, Huazhong University of Science and Technology, Wuhan, China

3Department of Respiratory and Critical Care Medicine, Wuhan Pulmonary Hospital, Wuhan, China

4Huazhong University of Science and Technology, Wuhan, China

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1Department of Pathophysiology, Huazhong University of Science and Technology, Wuhan, China

2Department of Respiratory and Critical Care Medicine, Huazhong University of Science and Technology, Wuhan, China

3Department of Respiratory and Critical Care Medicine, Wuhan Pulmonary Hospital, Wuhan, China

4Huazhong University of Science and Technology, Wuhan, China

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1Department of Pathophysiology, Huazhong University of Science and Technology, Wuhan, China

2Department of Respiratory and Critical Care Medicine, Huazhong University of Science and Technology, Wuhan, China

3Department of Respiratory and Critical Care Medicine, Wuhan Pulmonary Hospital, Wuhan, China

4Huazhong University of Science and Technology, Wuhan, China

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1Department of Pathophysiology, Huazhong University of Science and Technology, Wuhan, China

2Department of Respiratory and Critical Care Medicine, Huazhong University of Science and Technology, Wuhan, China

3Department of Respiratory and Critical Care Medicine, Wuhan Pulmonary Hospital, Wuhan, China

4Huazhong University of Science and Technology, Wuhan, China

Find articles by Ye, H. in: PubMed | Google Scholar |

1Department of Pathophysiology, Huazhong University of Science and Technology, Wuhan, China

2Department of Respiratory and Critical Care Medicine, Huazhong University of Science and Technology, Wuhan, China

3Department of Respiratory and Critical Care Medicine, Wuhan Pulmonary Hospital, Wuhan, China

4Huazhong University of Science and Technology, Wuhan, China

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Published October 16, 2025 - More info

J Clin Invest. https://doi.org/10.1172/JCI188822.
Copyright © 2025, Li et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published October 16, 2025 - Version history
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Abstract

The interaction between cells and extracellular matrix (ECM) has been recognized in mechanism of fibrotic diseases. Collagen type VII (collagen VII) is an ECM component which plays an important role in cell-ECM interaction, particularly in cell anchoring and maintaining ECM integrity. Pleural mesothelial cells (PMCs) drive inflammatory reactions and ECM production in pleura. However, the role of collagen VII and PMCs in pleural fibrosis was poorly understood. In this study, collagen VII protein was found increase in pleura of patients with tuberculous pleural fibrosis. Investigation of cellular and animal models revealed that collagen VII began to increase at early stage in pleural fibrotic process. Increase of collagen VII occurred ahead of collagen I and α-SMA in PMCs and pleura of animal models. Inhibition of collagen VII by mesothelial cell-specific deletion of collagen VII gene (WT1-Cre+-COL7A1flox/flox) attenuated mouse experimental pleural fibrosis. At last, it was found that excessive collagen VII changed collagen conformation which resulted in elevation of ECM stiffness. Elevation of ECM stiffness activated integrin/PI3K-AKT/JUN signaling and promoted more ECM deposition, as well as mediated pleural fibrosis. In conclusion, excessive collagen VII mediated pleural fibrosis via increasing extracellular matrix stiffness.

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  • Version 1 (October 16, 2025): In-Press Preview
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