2016 journal article
TAK1 regulates Paneth cell integrity partly through blocking necroptosis
CELL DEATH & DISEASE, 7.
MeSH headings : Animals; Anti-Bacterial Agents / pharmacology; Apoptosis / drug effects; Bacteria / drug effects; Bacteria / genetics; DNA, Bacterial / genetics; DNA, Bacterial / metabolism; Intestinal Mucosa / metabolism; Intestines / microbiology; Intestines / pathology; MAP Kinase Kinase Kinases / genetics; MAP Kinase Kinase Kinases / metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Myeloid Differentiation Factor 88 / deficiency; Myeloid Differentiation Factor 88 / genetics; Myeloid Differentiation Factor 88 / metabolism; Necrosis; Paneth Cells / drug effects; Paneth Cells / metabolism; Paneth Cells / pathology; RNA, Messenger / metabolism; Reactive Oxygen Species / metabolism; Real-Time Polymerase Chain Reaction; Receptor-Interacting Protein Serine-Threonine Kinases / genetics; Receptor-Interacting Protein Serine-Threonine Kinases / metabolism; Signal Transduction; Toll-Like Receptors / metabolism; Up-Regulation
TL;DR:
It is found that depletion of gut bacteria or myeloid differentiation factor 88 (Myd88), a mediator of bacteria-derived cell signaling, reduced ROS but did not block Paneth cell loss, suggesting that gut bacteria are the cause of ROS accumulation but bacteria-induced ROS are not the cause.
(via Semantic Scholar)
open access via www.nature.com (publisher PDF)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Source: Web Of Science
Added: August 6, 2018
AbstractPaneth cells reside at the base of crypts of the small intestine and secrete antimicrobial factors to control gut microbiota. Paneth cell loss is observed in the chronically inflamed intestine, which is often associated with increased reactive oxygen species (ROS). However, the relationship between Paneth cell loss and ROS is not yet clear. Intestinal epithelial-specific deletion of a protein kinase Tak1 depletes Paneth cells and highly upregulates ROS in the mouse model. We found that depletion of gut bacteria or myeloid differentiation factor 88 (Myd88), a mediator of bacteria-derived cell signaling, reduced ROS but did not block Paneth cell loss, suggesting that gut bacteria are the cause of ROS accumulation but bacteria-induced ROS are not the cause of Paneth cell loss. In contrast, deletion of the necroptotic cell death signaling intermediate, receptor-interacting protein kinase 3 (Ripk3), partially blocked Paneth cell loss. Thus, Tak1 deletion causes Paneth cell loss in part through necroptotic cell death. These results suggest that TAK1 participates in intestinal integrity through separately modulating bacteria-derived ROS and RIPK3-dependent Paneth cell loss.