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- Title
Metformin regulates tight junction of intestinal epithelial cells via MLCK-MLC signaling pathway.
- Authors
ZHOU, H.-Y.; ZHU, H.; YAO, X.-M.; QIAN, J.-P.; YANG, J.; PAN, X.-D.; CHEN, X.-D.
- Abstract
OBJECTIVE: To observe the effect of metformin on the tight junction of intestinal epithelial cells and its relevant mechanism. MATERIALS AND METHODS: Caco-2 cell monolayers were incubated with or without tumor necrosis factor-a (TNF-α) (10 ng/mL) in the absence or presence of indicated concentrations of metformin. Transepithelial electrical resistance (TEER) was measured at various time points. Caco-2 cell permeability was assessed using fluorescein permeability test. Immunofluorescence was used to detect the distribution of tight junction protein. Western blotting and Real-Time PCR were used to detect the expression of tight junction protein and Myosin light chain kinase (MLCK)-Myosin light chain (MLC) signaling pathway. RESULTS: Metformin attenuates the effects of TNF-α on Caco-2 cell TEER and paracellular permeability, prevents TNF-α-induced morphological disruption of tight junctions, ameliorates the inhibiting effect of TNF-α on epithelial tight junction-related protein expression and suppresses the TNF-α-induced increase in MLCK production. CONCLUSIONS: Metformin can stabilize and up-regulate tight junction protein by inhibiting MLCK-MLC signaling pathway, thus ameliorating the tight junction of intestinal epithelial cells.
- Subjects
METFORMIN; EPITHELIAL cells; MEMBRANE proteins; HEAT shock proteins; CELL proliferation
- Publication
European Review for Medical & Pharmacological Sciences, 2017, Vol 21, Issue 22, p5239
- ISSN
1128-3602
- Publication type
Article