RRC ID 59120
Author Patel PH, Pénalva C, Kardorff M, Roca M, Pavlović B, Thiel A, Teleman AA, Edgar BA.
Title Damage sensing by a Nox-Ask1-MKK3-p38 signaling pathway mediates regeneration in the adult Drosophila midgut.
Journal Nat Commun
Abstract Epithelia are exposed to diverse types of stress and damage from pathogens and the environment, and respond by regenerating. Yet, the proximal mechanisms that sense epithelial damage remain poorly understood. Here we report that p38 signaling is activated in adult Drosophila midgut enterocytes in response to diverse stresses including pathogenic bacterial infection and chemical and mechanical insult. Two upstream kinases, Ask1 and Licorne (MKK3), are required for p38 activation following infection, oxidative stress, detergent exposure and wounding. Ask1-p38 signaling in enterocytes is required upon infection to promote full intestinal stem cell (ISC) activation and regeneration, partly through Upd3/Jak-Stat signaling. Furthermore, reactive oxygen species (ROS) produced by the NADPH oxidase Nox in enterocytes, are required for p38 activation in enterocytes following infection or wounding, and for ISC activation upon infection or detergent exposure. We propose that Nox-ROS-Ask1-MKK3-p38 signaling in enterocytes integrates multiple different stresses to induce regeneration.
Volume 10(1)
Pages 4365
Published 2019-9-25
DOI 10.1038/s41467-019-12336-w
PII 10.1038/s41467-019-12336-w
PMID 31554796
PMC PMC6761285
MeSH Animals Animals, Genetically Modified Bacterial Infections / microbiology Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / genetics Drosophila melanogaster / metabolism Enterocytes / metabolism Enterocytes / microbiology Intestinal Mucosa / metabolism Intestinal Mucosa / microbiology Intestinal Mucosa / physiopathology Intestines / microbiology Intestines / pathology Intestines / physiopathology* MAP Kinase Kinase 3 / genetics MAP Kinase Kinase 3 / metabolism* MAP Kinase Kinase Kinases / genetics MAP Kinase Kinase Kinases / metabolism* NADPH Oxidases / genetics NADPH Oxidases / metabolism* Oxidative Stress Regeneration / genetics Regeneration / physiology* Signal Transduction* Stem Cells / metabolism Stem Cells / microbiology Stress, Mechanical p38 Mitogen-Activated Protein Kinases / genetics p38 Mitogen-Activated Protein Kinases / metabolism*
IF 11.878
Times Cited 7