Sodium Propionate Attenuates the Lipopolysaccharide-Induced Epithelial-Mesenchymal Transition via the PI3K/Akt/mTOR Signaling Pathway

• Published in: Journal of agricultural and food chemistry 2020-06, Vol.68 (24), p.6554-6563
• Main Authors: Chen, Dan, Qiu, Yu-Bao, Gao, Zhi-Qi, Wu, Ya-Xian, Wan, Bin-Bin, Liu, Gang, Chen, Jun-Liang, Zhou, Qin, Yu, Ren-Qiang, Pang, Qing-Feng
• Format: Article
• Language: English
• Subjects: Actins - genetics; Actins - metabolism; Animals; Cadherins - genetics; Cadherins - metabolism; Epithelial-Mesenchymal Transition - drug effects; Humans; Lipopolysaccharides - pharmacology; Lung Diseases - drug therapy; Lung Diseases - genetics; Lung Diseases - metabolism; Lung Diseases - physiopathology; Male; Mice; Phosphatidylinositol 3-Kinase - genetics; Phosphatidylinositol 3-Kinase - metabolism; Propionates - administration & dosage; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction - drug effects; TOR Serine-Threonine Kinases - genetics; TOR Serine-Threonine Kinases - metabolism; Vimentin - genetics; Vimentin - metabolism
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/acs.jafc.0c01302

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 ( < 0.05), 1.04 ± 0.30 ( < 0.05), and 0.96 ± 0.13 ( < 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.