PADs and NETs in digestive system: From physiology to pathology

Front Immunol. 2023 Jan 24:14:1077041. doi: 10.3389/fimmu.2023.1077041. eCollection 2023.

Abstract

Peptidylarginine deiminases (PADs) are the only enzyme class known to deiminate arginine residues into citrulline in proteins, a process known as citrullination. This is an important post-translational modification that functions in several physiological and pathological processes. Neutrophil extracellular traps (NETs) are generated by NETosis, a novel cell death in neutrophils and a double-edged sword in inflammation. Excessive activation of PADs and NETs is critically implicated in their transformation from a physiological to a pathological state. Herein, we review the physiological and pathological functions of PADs and NETs, in particular, the involvement of PAD2 and PAD4 in the digestive system, from inflammatory to oncological diseases, along with related therapeutic prospects.

Keywords: cancer; citrullination; digestive system; inflammation; peptidylarginine deiminase.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Citrullination
  • Digestive System / metabolism
  • Extracellular Traps* / metabolism
  • Hydrolases / genetics
  • Protein-Arginine Deiminases / genetics

Substances

  • Protein-Arginine Deiminases
  • Hydrolases

Grants and funding

Author S-LW is supported by the National Natural Science Foundation of China (No. 82100587), the Shanghai Sailing Program (No. 21YF1458700), China National Postdoctoral Program for Innovative Talents (No. BX20220288) and China Postdoctoral Science Foundation (No. 2022M720138). Author YB is supported by the National Natural Science Foundation of China (No.82170567, 81873546), Program of Shanghai Academic Research Leader (No. 22XD1425000) and Deep Blue Project of Naval Medical University (Pilot Talent Plan).