Mesenchymal Stromal Cells Accelerate Epithelial Tight Junction Assembly via the AMP-Activated Protein Kinase Pathway, Independently of Liver Kinase B1 - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Stem Cells International Année : 2017

Mesenchymal Stromal Cells Accelerate Epithelial Tight Junction Assembly via the AMP-Activated Protein Kinase Pathway, Independently of Liver Kinase B1

Résumé

Background. Mesenchymal stromal cells (MSC) are fibroblast-like multipotent cells capable of tissue-repair properties. Given the essentiality of tight junctions (TJ) in epithelial integrity, we hypothesized that MSC modulate TJ formation, via the AMP-activated kinase (AMPK) pathway. Liver kinase-β1 (LKB1) and Ca 2+-calmodulin-dependent protein kinase kinase (CaMKK) represent the main kinases that activate AMPK. Methods. The in vitro Ca 2+ switch from 5 μM to 1.8 mM was performed using epithelial Madin-Darby canine kidney (MDCK) cells cultured alone or cocultured with rat bone marrow-derived MSC or preexposed to MSC-conditioned medium. TJ assembly was measured by assessing ZO-1 relocation to cell-cell contacts. Experiments were conducted using MDCK stably expressing short-hairpin-RNA (shRNA) against LKB1 or luciferase (LUC, as controls). Compound STO-609 (50 μM) was used as CaMKK inhibitor. Results. Following Ca 2+ switch, ZO-1 relocation and phosphorylation/activation of AMPK were significantly higher in MDCK/MSC compared to MDCK. No difference in AMPK phosphorylation was observed between LKB1-shRNA and Luc-shRNA MDCK following Ca 2+ switch. Conversely, incubation with STO-609 prior to Ca 2+ switch prevented AMPK phosphorylation and ZO-1 relocation. MSC-conditioned medium slightly but significantly increased AMPK activation and accelerated TJ-associated distribution of ZO-1 post Ca 2+ switch in comparison to regular medium. Conclusions. MSC modulate the assembly of epithelial TJ, via the CaMKK/AMPK pathway independently of LKB1.
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Dates et versions

hal-01787956 , version 1 (07-05-2018)

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  • HAL Id : hal-01787956 , version 1

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P Rowart, P Erpicum, J.-M Krzesinski, M Sebbagh, F Jouret. Mesenchymal Stromal Cells Accelerate Epithelial Tight Junction Assembly via the AMP-Activated Protein Kinase Pathway, Independently of Liver Kinase B1. Stem Cells International, 2017. ⟨hal-01787956⟩
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