P2Y2 purinergic receptor gene deletion protects mice from bacterial endotoxin and sepsis-associated liver injury and mortality

Author:

Arunachalam Athis R.1,Samuel Sanju S.2,Mani Arunmani3,Maynard Janielle P.3ORCID,Stayer Kelsey M.2,Dybbro Eric3,Narayanan Subapradha3,Biswas Aalekhya3,Pathan Saliha3,Soni Krishnakant3,Kamal Abu Hena Mostafa4,Ambati Chandra Shekar R.5,Putluri Nagireddy4,Desai Moreshwar S.2ORCID,Thevananther Sundararajah3ORCID

Affiliation:

1. Neonatology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States

2. Critical Care Medicine, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States

3. Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States

4. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, United States

5. Advanced Technology Core, Baylor College of Medicine, Houston, Texas, United States

Abstract

Our studies provide experimental evidence for P2Y2 purinergic receptor-mediated potentiation of inflammatory liver injury, morbidity, and mortality, in two well-established animal models of inflammatory liver injury. Our findings highlight the potential to target P2Y2 purinergic signaling to attenuate the induction of “cytokine storm” and prevent its deleterious consequences on liver function, systemic amino acid homeostasis, host response to bacterial infection, and sepsis-associated morbidity and mortality.

Funder

HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases

Baylor College of Medicine

Cancer Prevention and Research Institute of Texas

Dan L. Duncan Cancer Center, Baylor College of Medicine

HHS | NIH | National Cancer Institute

Publisher

American Physiological Society

Subject

Physiology (medical),Gastroenterology,Hepatology,Physiology

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