1. Sodium Propionate Attenuates the Lipopolysaccharide-Induced Epithelial-Mesenchymal Transition via the PI3K/Akt/mTOR Signaling Pathway.
- Author
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Chen D, Qiu YB, Gao ZQ, Wu YX, Wan BB, Liu G, Chen JL, Zhou Q, Yu RQ, and Pang QF
- Subjects
- Actins genetics, Actins metabolism, Animals, Cadherins genetics, Cadherins metabolism, Humans, Lung Diseases genetics, Lung Diseases metabolism, Lung Diseases physiopathology, Male, Mice, Phosphatidylinositol 3-Kinase genetics, Proto-Oncogene Proteins c-akt genetics, Signal Transduction drug effects, TOR Serine-Threonine Kinases genetics, TOR Serine-Threonine Kinases metabolism, Vimentin genetics, Vimentin metabolism, Epithelial-Mesenchymal Transition drug effects, Lipopolysaccharides pharmacology, Lung Diseases drug therapy, Phosphatidylinositol 3-Kinase metabolism, Propionates administration & dosage, Proto-Oncogene Proteins c-akt metabolism
- Abstract
Short-chain fatty acids (SCFAs), especially propionate, originate from the fermentation of dietary fiber in the gut and play a key role in inhibiting pulmonary inflammation. Chronic inflammation may induce an epithelial-mesenchymal transition (EMT) in alveolar epithelial cells and result in fibrotic disorders. This study was designed to investigate the beneficial effect of sodium propionate (SP) on lipopolysaccharide (LPS)-induced EMT. In cultured BEAS-2B cells, the protein expression levels of E-cadherin, α-smooth muscle actin (SMA), and vimentin were 0.66 ± 0.20, 1.44 ± 0.23, and 1.32 ± 0.21 in the LPS group vs 1.11 ± 0.36 ( P < 0.05), 1.04 ± 0.30 ( P < 0.05), and 0.96 ± 0.13 ( P < 0.01) in the LPS + SP group (mean ± standard deviation), respectively. Meanwhile, LPS-triggered inflammatory cytokines and extracellular proteins were also reduced by SP administration in BEAS-2B cells. Moreover, SP treatment attenuated inflammation, EMT, extracellular matrix (ECM) deposition, and even fibrosis in a mouse EMT model. In terms of mechanism, LPS-treated BEAS-2B cells exhibited a higher level of phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) phosphorylation, which was interrupted by SP treatment. It is worth noting that the blockade of the PI3K/Akt/mTOR signaling cascade reduced the LPS-evoked EMT process in BEAS-2B cells. These results suggest that SP can block LPS-induced EMT via inhibition of the PI3K/Akt/mTOR signaling cascade, which provides a basis for possible clinical use of SP in airway and lung diseases.
- Published
- 2020
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