In this Issue
THEMES | Neuroimmune Cross Talk in the Gut
RESEARCH ARTICLE | Epithelial Biology and Secretion
- Computational modeling of epithelial fluid and ion transport in the parotid duct after transfection of human aquaporin-1
Following transfection of aquaporin into the parotid ducts of minipigs with salivary hypofunction, the resulting increase in salivary flow rates contradicts current understanding of ductal fluid transport. We show that the change in saliva electrochemistry and flow rate can be explained by changes in expression of ion transporters in the ductal cell membranes, using a mathematical model replicating a single parotid duct.
RESEARCH ARTICLE | Hormones, Neurotransmitters, Growth Factors, Receptors, and Signaling
- Neuropeptide Y (NPY) promotes inflammation-induced tumorigenesis by enhancing epithelial cell proliferation
Our work exemplifies a novel role of neuropeptide Y (NPY) in regulating inflammation-induced tumorigenesis via two modalities: first by enhanced proliferation (PI3-K/pAkt), and second by downregulation of microRNA-375 (miR-375)-dependent apoptosis in intestinal epithelial cells. Our data establish the existence of a microRNA-mediated cross talk between enteric neurons producing NPY and intestinal epithelial cells, and the potential of neuropeptide-regulated miRNAs as potential therapeutic molecules for the management of inflammation-associated tumors in the gut.
RESEARCH ARTICLE | Inflammation, Immunity, Fibrosis, and Infection
- miR-200b inhibits TNF-α-induced IL-8 secretion and tight junction disruption of intestinal epithelial cells in vitro
This was the first time that the inhibitory role of microRNA (miR)-200b on intestinal epithelial inflammation and paracellular permeability has been reported. Moreover, we further divided the intestinal epithelial cells (IECs) into two differentiated conditions and investigated the distinct impacts of miR-200b. Finally, we put forward and proved that myosin light chain kinase (MLCK) was a novel target of miR-200b.
RESEARCH ARTICLE | Microbiome and Host Interactions
- Critical role of microbiota within cecal crypts on the regenerative capacity of the intestinal epithelium following surgical stress
This study provides novel insight into the process by which surgical injury places the intestinal epithelium at risk for colonization by pathogenic microbes and impairment of its regenerative capacity via loss of its microbiota. We show that fecal transplant restores crypt homeostasis in association with repopulation of the microbiota within cecal crypts.
RESEARCH ARTICLE | Stem Cells, Tissue Engineering, Development, and Cancer
- NOTCH1 and NOTCH2 regulate epithelial cell proliferation in mouse and human gastric corpus
Here we demonstrate that the Notch signaling pathway is essential for proliferation of stem cells in the mouse and human gastric corpus. We identify NOTCH1 and NOTCH2 as the predominant Notch receptors expressed in both mouse and human corpus and show that both receptors are required for corpus stem cell proliferation. We show that chronic Notch activation in corpus stem cells induces hyperproliferation and tissue hypertrophy, suggesting that Notch may drive gastric tumorigenesis.