Abstract
Background: The role of purinergic P2X7 receptor (P2X7R) is of interest due to its involvement in inflammation and mediating immune cell responses. P2X7R is particularly implicated in the development of inflammatory bowel disease (IBD). However, the extent of the actions of P2X7R in the gastrointestinal (GI) system under physiological and pathophysiological conditions remains to be elucidated. This systematic review aimed to identify, summarize and evaluate the evidence for a critical role of P2X7R in the GI system. Methods: We searched PubMed, Embase and Scopus with search terms pertained to P2X7R in the GI system in disease or physiological state, including “P2X7 or P2X7 receptor or purinergic signaling” in combination with any of the terms “intestine or colon or gut or gastrointestinal,” “pathology or inflammation or disease or disorder,” and “physiology or expression.” Titles and abstracts were screened for potentially eligible full texts, and animal and human studies published in English were included in this study. Data were extracted from papers meeting inclusion criteria. Meta-analysis was not feasible given the study diversity. Results: There were 48 papers included in this review. We identified 14 experimental colitis models, three sepsis models and one ischemia-reperfusion injury model. Among them, 11 studies examined P2X7R in GI infections, six studies on immune cell regulation, four studies on GI inflammation, two studies on GI malignancies, three studies involving intestinal injury due to various causes, two studies on ATP-activated P2X7R in the GI system and two studies on metabolic regulation. Conclusion: Evidence supports P2X7R mediating inflammation and immune cell responses in GI inflammation, infections and injury due to IBD and other challenges to the intestinal wall. P2X7R inhibition by gene knockout or by application of P2X7R antagonists can reduce tissue damage by suppressing inflammation. P2X7R is also implicated in GI malignancies and glucose and lipid homeostasis. P2X7R blockade, however, did not always lead to beneficial outcomes in the various pathological models of study.
Highlights
Extracellular adenosine triphosphate (ATP) is recognized as an important signaling molecule; it is involved in basic physiological and pathophysiological processes such as tissue homeostasis, wound healing, neurodegeneration, immune and inflammatory responses and cancer (Di Virgilio and Adinolfi, 2016)
We identified 14 experimental colitis models, three sepsis models and one ischemia-reperfusion injury model
P2X7 receptor (P2X7R) activation has been shown to induce a broad array of cellular responses, including cytokine release, apoptosis, and cell death, which are associated with inflammatory processes
Summary
Extracellular adenosine triphosphate (ATP) is recognized as an important signaling molecule; it is involved in basic physiological and pathophysiological processes such as tissue homeostasis, wound healing, neurodegeneration, immune and inflammatory responses and cancer (Di Virgilio and Adinolfi, 2016). Despite being a ubiquitous molecule, ATP acts as a co-transmitter in the peripheral and central nervous system (Burnstock, 2012) and it is involved in various cellular responses, including upregulating or inhibiting cell death, regulating growth factors and inflammatory mediators (Di Virgilio and Adinolfi, 2016). Short- and long-term purinergic signaling is involved in physiological and pathophysiological processes. This systematic review aimed to identify, summarize and evaluate the evidence for a critical role of P2X7R in the GI system
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
