| Title: |
Mesenchymal Stromal Cells Accelerate Epithelial Tight Junction Assembly via the AMP-Activated Protein Kinase Pathway, Independently of Liver Kinase B1 |
| Authors: |
Rowart, P; Erpicum, P; Krzesinski, J.-M; Sebbagh, M; Jouret, F |
| Contributors: |
Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA-Research); Université de Liège = University of Liège = Universiteit van Luik = Universität Lüttich (ULiège); Centre de Recherche en Cancérologie de Marseille (CRCM); Aix Marseille Université (AMU)-Institut Paoli-Calmettes (IPC); Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Source: |
ISSN: 1687-966X. |
| Publisher Information: |
CCSD; Hindawi Publishing Corporation |
| Publication Year: |
2017 |
| Collection: |
Aix-Marseille Université: HAL |
| Subject Terms: |
[SDV]Life Sciences [q-bio] |
| Description: |
International audience ; 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Availability: |
https://hal.science/hal-01787956; https://hal.science/hal-01787956v1/document; https://hal.science/hal-01787956v1/file/mesemchymal%20stromal%20cells.pdf |
| Rights: |
https://about.hal.science/hal-authorisation-v1/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.4BB9F049 |
| Database: |
BASE |