Single‐cell RNA sequencing reveals the effects of capsaicin in the treatment of sepsis‐induced liver injury
Qian Zhang,
Jing Liu,
Jing Shen,
Jinhuan Ou,
Yin Kwan Wong,
Lulin Xie,
Jingnan Huang,
Chunting Zhang,
Chunjin Fu,
Junhui Chen,
Jiayun Chen,
Xueling He,
Fei Shi,
Piao Luo,
Ping Gong,
Xueyan Liu,
Jigang Wang
Affiliations
Qian Zhang
Department of Critical Medicine, and Shenzhen Clinical Research Centre for Geriatrics Shenzhen People's Hospital First Affiliated Hospital of Southern University of Science and Technology Second Clinical Medicine College of Jinan University Shenzhen Guangdong China
Jing Liu
Department of Critical Medicine, and Shenzhen Clinical Research Centre for Geriatrics Shenzhen People's Hospital First Affiliated Hospital of Southern University of Science and Technology Second Clinical Medicine College of Jinan University Shenzhen Guangdong China
Jing Shen
Department of Oncology Shenzhen People's Hospital The First Affiliated Hospital Southern University of Science and Technology Shenzhen Guangdong China
Jinhuan Ou
Department of Critical Medicine, and Shenzhen Clinical Research Centre for Geriatrics Shenzhen People's Hospital First Affiliated Hospital of Southern University of Science and Technology Second Clinical Medicine College of Jinan University Shenzhen Guangdong China
Yin Kwan Wong
Department of Physiology Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore
Lulin Xie
Department of Critical Medicine, and Shenzhen Clinical Research Centre for Geriatrics Shenzhen People's Hospital First Affiliated Hospital of Southern University of Science and Technology Second Clinical Medicine College of Jinan University Shenzhen Guangdong China
Jingnan Huang
Department of Critical Medicine, and Shenzhen Clinical Research Centre for Geriatrics Shenzhen People's Hospital First Affiliated Hospital of Southern University of Science and Technology Second Clinical Medicine College of Jinan University Shenzhen Guangdong China
Chunting Zhang
Department of Critical Medicine, and Shenzhen Clinical Research Centre for Geriatrics Shenzhen People's Hospital First Affiliated Hospital of Southern University of Science and Technology Second Clinical Medicine College of Jinan University Shenzhen Guangdong China
Chunjin Fu
Department of Critical Medicine, and Shenzhen Clinical Research Centre for Geriatrics Shenzhen People's Hospital First Affiliated Hospital of Southern University of Science and Technology Second Clinical Medicine College of Jinan University Shenzhen Guangdong China
Junhui Chen
Department of Critical Medicine, and Shenzhen Clinical Research Centre for Geriatrics Shenzhen People's Hospital First Affiliated Hospital of Southern University of Science and Technology Second Clinical Medicine College of Jinan University Shenzhen Guangdong China
Jiayun Chen
State Key Laboratory for Quality Ensurance and Sustainable Use of Dao‐di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing China
Xueling He
State Key Laboratory for Quality Ensurance and Sustainable Use of Dao‐di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing China
Fei Shi
Department of Infectious Disease Shenzhen People's Hospital The First Affiliated Hospital Southern University of Science and Technology Shenzhen Guangdong China
Piao Luo
Department of Critical Medicine, and Shenzhen Clinical Research Centre for Geriatrics Shenzhen People's Hospital First Affiliated Hospital of Southern University of Science and Technology Second Clinical Medicine College of Jinan University Shenzhen Guangdong China
Ping Gong
Department of Emergency Shenzhen People's Hospital The First Affiliated Hospital Southern University of Science and Technology Shenzhen City Guangdong Province China
Xueyan Liu
Department of Critical Medicine, and Shenzhen Clinical Research Centre for Geriatrics Shenzhen People's Hospital First Affiliated Hospital of Southern University of Science and Technology Second Clinical Medicine College of Jinan University Shenzhen Guangdong China
Jigang Wang
Department of Critical Medicine, and Shenzhen Clinical Research Centre for Geriatrics Shenzhen People's Hospital First Affiliated Hospital of Southern University of Science and Technology Second Clinical Medicine College of Jinan University Shenzhen Guangdong China
Abstract Sepsis is a difficult‐to‐treat systemic condition in which liver dysfunction acts as both regulator and target. However, the dynamic response of diverse intrahepatic cells to sepsis remains poorly characterized. Capsaicin (CAP), a multifunctional chemical derived from chilli peppers, has recently been shown to potentially possess anti‐inflammatory effects, which is also one of the main approaches for drug discovery against sepsis. We performed single‐cell RNA transcriptome sequencing on 86,830 intrahepatic cells isolated from normal mice, cecal ligation and puncture‐induced sepsis model mice and CAP‐treated mice. The transcriptional atlas of these cells revealed dynamic changes in hepatocytes, macrophages, neutrophils, and endothelial cells in response to sepsis. Among the extensive crosstalk across these major subtypes, KC_Cxcl10 shared strong potential interaction with other cells when responding to sepsis. CAP mitigated the severity of inflammation by partly reversing these pathophysiologic processes. Specific cell subpopulations in the liver act collectively to escalate inflammation, ultimately causing liver dysfunction. CAP displays its health‐promoting function by ameliorating liver dysfunction induced by sepsis. Our study provides valuable insights into the pathophysiology of sepsis and suggestions for future therapeutic gain.
