In this Issue
March 2017; volume 312, issue 3
THEMES | Neuroimmune Cross Talk in the Gut
REVIEW | Microbiome and Host Interactions
REVIEW | Stem Cells, Tissue Engineering, Development, and Cancer
MINI-REVIEWS | Liver and Biliary Tract Physiology/Pathophysiology
MINI-REVIEW | Neurogastroenterology and Motility
RESEARCH ARTICLE | Inflammation, Immunity, Fibrosis, and Infection
- Enteric glia cells are critical to limiting the intestinal inflammatory response after injury
Intestinal inflammation is initiated by local immune cell activation and epithelial barrier breakdown, resulting in the production of proinflammatory mediators with subsequent leukocyte recruitment. Vagal nerve stimulation (VNS) has been shown to limit intestinal inflammation following injury; however, a direct connection between vagal terminals and resident intestinal immune cells has yet to be identified. Here, we demonstrate that intact enteric glia cells are required to transmit the gut anti-inflammatory effects of VNS.
RESEARCH ARTICLES | Liver and Biliary Tract Physiology/Pathophysiology
- Protective roles of hepatic GABA signaling in acute liver injury of rats
Auto- and paracrine GABAergic signaling systems exist in the rat hepatocytes and cholangiocytes. Activation of GABA signaling protects liver function from d-galactosamine injury by reducing toxic impairment of hepatocytes and by decreasing cholangiocyte proliferation.
- WNT-5A regulates TGF-β-related activities in liver fibrosis
This study describes the localization and functional role of WNT-5A in human and mouse fibrotic livers. Hepatic WNT-5A expression parallels collagen type I expression. In vivo and in vitro, the myofibroblasts were identified as the key hepatic cells producing WNT-5A. WNT-5A is under control of TGF-β and its activities are primarily profibrotic.
- Inhibition of sphingosine 1-phosphate signaling ameliorates murine nonalcoholic steatohepatitis
There are no approved pharmacologic therapies for nonalcoholic steatohepatitis (NASH), the leading cause of chronic liver disease worldwide. This study describes the use of FTY720, a novel small molecule, for the amelioration of NASH in a mouse model. We demonstrate that 2-wk administration of FTY720 to mice with NASH led to a reduction in liver injury, inflammation, and fibrosis. These data provide preclinical rationale for studying this drug in human NASH.
RESEARCH ARTICLE | Neurogastroenterology and Motility
- Conditional genetic deletion of Ano1 in interstitial cells of Cajal impairs Ca2+ transients and slow waves in adult mouse small intestine
The Ca2+-activated Cl− channel, Ano1, in interstitial cells of Cajal (ICC) is necessary for normal gastrointestinal motility. We knocked out Ano1 to varying degrees in ICC of adult mice. Partial knockout of Ano1 shortened the widths of electrical slow waves and Ca2+ transients in myenteric ICC but Ca2+ transient synchronicity was preserved. Near-complete knockout was necessary for transient desynchronization and loss of slow waves, indicating a large functional reserve of Ano1 in ICC.
RESEARCH ARTICLE | Pancreatic Physiology/Pathophysiology
- RCAD/BiP pathway is necessary for the proper synthesis of digestive enzymes and secretory function of the exocrine pancreas
RCAD/BiP pathway is required for the proper synthesis and secretion of amylase from pancreatic acini, as well as for the maintenance of the ER homeostasis. In alcoholism, the exocrine pancreas could increase the levels of components of the Ufm1 system to protect itself from alcohol's deleterious effects by regulating the expression of ER chaperone BiP.