Sox9-expressing cells promote regeneration after radiation-induced lung injury via the PI3K/AKT pathway.
Shuang Chen, Kang Li, Xinqi Zhong, Ganping Wang, Xiaocheng Wang, Maosheng Cheng, Jie Chen, Zhi Chen, Jianwen Chen, Caihua Zhang, Gan Xiong, Xiuyun Xu, Demeng Chen, Heping Li, Liang Peng
Author Information
Shuang Chen: Center for Translational Medicine, Institute of Precision Medicine, Department of Medical Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
Kang Li: Center for Translational Medicine, Institute of Precision Medicine, Department of Medical Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
Xinqi Zhong: Department of Neonatology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Ganping Wang: Center for Translational Medicine, Institute of Precision Medicine, Department of Medical Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
Xiaocheng Wang: Center for Translational Medicine, Institute of Precision Medicine, Department of Medical Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
Maosheng Cheng: Center for Translational Medicine, Institute of Precision Medicine, Department of Medical Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
Jie Chen: Center for Translational Medicine, Institute of Precision Medicine, Department of Medical Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
Zhi Chen: Center for Translational Medicine, Institute of Precision Medicine, Department of Medical Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
Jianwen Chen: Center for Translational Medicine, Institute of Precision Medicine, Department of Medical Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
Caihua Zhang: Center for Translational Medicine, Institute of Precision Medicine, Department of Medical Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
Gan Xiong: Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, 510030, China.
Xiuyun Xu: Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, 510030, China.
Demeng Chen: Center for Translational Medicine, Institute of Precision Medicine, Department of Medical Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. chendm29@mail.sysu.edu.cn.
Heping Li: Center for Translational Medicine, Institute of Precision Medicine, Department of Medical Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. liheping@mail.sysu.edu.cn.
Liang Peng: Oncology Department, Chinese PLA General Hospital, Beijing, 100000, China. pengliang@301hospital.com.cn.
BACKGROUND: Radiation-induced lung injury (RILI) is considered one of the most common complications of thoracic radiation. Recent studies have focused on stem cell properties to obtain ideal therapeutic effects, and Sox9 has been reported to be involved in stem cell induction and differentiation. However, whether Sox9-expressing cells play a role in radiation repair and regeneration remains unknown. METHODS: We successfully obtained Sox9, Rosa and Rosa mice and identified Sox9-expressing cells through lineage tracing. Then, we evaluated the effects of the ablation of Sox9-expressing cells in vivo. Furthermore, we investigated the underlying mechanism of Sox9-expressing cells during lung regeneration via an online single-cell RNA-seq dataset. RESULTS: In our study, we demonstrated that Sox9-expressing cells promote the regeneration of lung tissues and that ablation of Sox9-expressing cells leads to severe phenotypes after radiation damage. In addition, analysis of an online scRNA-Seq dataset revealed that the PI3K/AKT pathway is enriched in Sox9-expressing cells during lung epithelium regeneration. Finally, the AKT inhibitor perifosine suppressed the regenerative effects of Sox9-expressing cells and the AKT pathway agonist promotes proliferation and differentiation. CONCLUSIONS: Taken together, the findings of our study suggest that Sox9-expressing cells may serve as a therapeutic target in lung tissue after RILI.
