| First Author | Feng Y | Year | 2015 |
| Journal | Mol Cell Biol | Volume | 35 |
| Issue | 21 | Pages | 3604-21 |
| PubMed ID | 26283731 | Mgi Jnum | J:228217 |
| Mgi Id | MGI:5705679 | Doi | 10.1128/MCB.00143-15 |
| Citation | Feng Y, et al. (2015) Loss of ADAM17-Mediated Tumor Necrosis Factor Alpha Signaling in Intestinal Cells Attenuates Mucosal Atrophy in a Mouse Model of Parenteral Nutrition. Mol Cell Biol 35(21):3604-21 |
| abstractText | Total parenteral nutrition (TPN) is commonly used clinically to sustain patients; however, TPN is associated with profound mucosal atrophy, which may adversely affect clinical outcomes. Using a mouse TPN model, removing enteral nutrition leads to decreased crypt proliferation, increased intestinal epithelial cell (IEC) apoptosis and increased mucosal tumor necrosis factor alpha (TNF-alpha) expression that ultimately produces mucosal atrophy. Upregulation of TNF-alpha signaling plays a central role in mediating TPN-induced mucosal atrophy without intact epidermal growth factor receptor (EGFR) signaling. Currently, the mechanism and the tissue-specific contributions of TNF-alpha signaling to TPN-induced mucosal atrophy remain unclear. ADAM17 is an ectodomain sheddase that can modulate the signaling activity of several cytokine/growth factor receptor families, including the TNF-alpha/TNF receptor and ErbB ligand/EGFR pathways. Using TPN-treated IEC-specific ADAM17-deficient mice, the present study demonstrates that a loss of soluble TNF-alpha signaling from IECs attenuates TPN-induced mucosal atrophy. Importantly, this response remains dependent on the maintenance of functional EGFR signaling in IECs. TNF-alpha blockade in wild-type mice receiving TPN confirmed that soluble TNF-alpha signaling is responsible for downregulation of EGFR signaling in IECs. These results demonstrate that ADAM17-mediated TNF-alpha signaling from IECs has a significant role in the development of the proinflammatory state and mucosal atrophy observed in TPN-treated mice. |
