DLL4-Notch signalling in acute-on-chronic liver failure: State of the art and perspectives.

Qian Zhou, Bingqi Li, Jun Li

Journal: Life sciences 2023;317():121438

PMID: 36709913

Full Text on Elsevier Science View on PubMed

Abstract

Acute-on-chronic liver failure (ACLF) is a syndrome characterized by acute decompensation of chronic liver disease associated with multiple-organ failures and high short-term mortality. Acute insults to patients with chronic liver disease can lead to ACLF, among which, hepatitis B virus-related ACLF is the most common type of liver failure in the Asia-Pacific region. Currently, immune-metabolism disorders and systemic inflammation are proposed to be the main mechanisms of ACLF. The resulting cholestasis and intrahepatic microcirculatory dysfunction accelerate the development of ACLF. Treatments targeting immune regulation, metabolic balance, microcirculation maintenance and bile duct repair can alleviate inflammation and restore the tissue structure. An increasing number of studies have demonstrated that delta-like ligand 4 (DLL4), one of the Notch signalling ligands, plays a vital role in immune regulation, metabolism, angiogenesis, and biliary regeneration, which participate in liver pathological and physiological processes. The detailed mechanism of the DLL4-Notch signalling pathway in ACLF has rarely been investigated. Here, we review the evidence showing that DLL4-Notch signalling is involved in ACLF and analyse the potential role of DLL4 in the treatment of ACLF.

Address: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Centre for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou 310003, China.; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Centre for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou 310003, China; Precision Medicine Center of Taizhou Central Hospital, Taizhou University Medical School, Taizhou, China. Electronic address: [email protected].

DOI: 10.1016/j.lfs.2023.121438

Link outs

Subscription / membership required

Full Text Sources:

MeSH Terms: Humans, Acute-On-Chronic Liver Failure, Liver Cirrhosis, Microcirculation, Inflammation, Signal Transduction, Calcium-Binding Proteins, Adaptor Proteins, Signal Transducing