TY  - JOUR
A1  - Meir, Michael
A1  - Kannapin, Felix
A1  - Diefenbacher, Markus
A1  - Ghoreishi, Yalda
A1  - Kollmann, Catherine
A1  - Flemming, Sven
A1  - Germer, Christoph-Thomas
A1  - Waschke, Jens
A1  - Leven, Patrick
A1  - Schneider, Reiner
A1  - Wehner, Sven
A1  - Burkard, Natalie
A1  - Schlegel, Nicolas
T1  - Intestinal epithelial barrier maturation by enteric glial cells is GDNF-dependent
JF  - International Journal of Molecular Sciences
N2  - Enteric glial cells (EGCs) of the enteric nervous system are critically involved in the maintenance of intestinal epithelial barrier function (IEB). The underlying mechanisms remain undefined. Glial cell line-derived neurotrophic factor (GDNF) contributes to IEB maturation and may therefore be the predominant mediator of this process by EGCs. Using GFAP\(^{cre}\) x Ai14\(^{floxed}\) mice to isolate EGCs by Fluorescence-activated cell sorting (FACS), we confirmed that they synthesize GDNF in vivo as well as in primary cultures demonstrating that EGCs are a rich source of GDNF in vivo and in vitro. Co-culture of EGCs with Caco2 cells resulted in IEB maturation which was abrogated when GDNF was either depleted from EGC supernatants, or knocked down in EGCs or when the GDNF receptor RET was blocked. Further, TNFα-induced loss of IEB function in Caco2 cells and in organoids was attenuated by EGC supernatants or by recombinant GDNF. These barrier-protective effects were blunted when using supernatants from GDNF-deficient EGCs or by RET receptor blockade. Together, our data show that EGCs produce GDNF to maintain IEB function in vitro through the RET receptor.
KW  - enteric glial cells
KW  - neurotrophic factors
KW  - intestinal epithelial barrier
KW  - GDNF5
KW  - RET6
KW  - inflammatory bowel disease
KW  - enteric nervous system
KW  - gut barrier
KW  - intercellular junctions
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258913
SN  - 1422-0067
VL  - 22
IS  - 4
ER  -