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Fibronectin-integrin signaling is required for L-glutamine's protection against gut injury.

Authors: Niederlechner, S  Klawitter, J  Baird, C  Kallweit, AR  Christians, U  Wischmeyer, PE 
Citation: Niederlechner S, etal., PLoS One. 2012;7(11):e50185. doi: 10.1371/journal.pone.0050185. Epub 2012 Nov 20.
Pubmed: (View Article at PubMed) PMID:23185570
DOI: Full-text: DOI:10.1371/journal.pone.0050185

BACKGROUND: Extracellular matrix (ECM) stabilization and fibronectin (FN)-Integrin signaling can mediate cellular protection. L-glutamine (GLN) is known to prevent apoptosis after injury. However, it is currently unknown if ECM stabilization and FN-Integrin osmosensing pathways are related to GLN's cell protective mechanism in the intestine. METHODS: IEC-6 cells were treated with GLN with or without FN siRNA, integrin inhibitor GRGDSP, control peptide GRGESP or ERK1/2 inhibitors PD98059 and UO126 under basal and stressed conditions. Cell survival measured via MTS assay. Phosphorylated and/or total levels of cleaved caspase-3, cleaved PARP, Bax, Bcl-2, heat shock proteins (HSPs), ERK1/2 and transcription factor HSF-1 assessed via Western blotting. Cell size and F-actin morphology quantified by confocal fluorescence microscopy and intracellular GLN concentration by LC-MS/MS. RESULTS: GLN's prevention of FN degradation after hyperthermia attenuated apoptosis. Additionally, inhibition of FN-Integrin interaction by GRGDSP and ERK1/2 kinase inhibition by PD98059 inhibited GLN's protective effect. GRGDSP attenuated GLN-mediated increases in ERK1/2 phosphorylation and HSF-1 levels. PD98059 and GRGDSP also decreased HSP levels after GLN treatment. Finally, GRGDSP attenuated GLN-mediated increases in cell area size and disrupted F-actin assembly, but had no effect on intracellular GLN concentrations. CONCLUSION: Taken together, this data suggests that prevention of FN degradation and the FN-Integrin signaling play a key role in GLN-mediated cellular protection. GLN's signaling via the FN-Integrin pathway is associated with HSP induction via ERK1/2 and HSF-1 activation leading to reduced apoptosis after gut injury.


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CRRD Object Information
CRRD ID: 10450472
Created: 2016-01-13
Species: All species
Last Modified: 2016-01-13
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.