Propionate regulates tight junction barrier by increasing endothelial-cell selective adhesion molecule in human intestinal Caco-2 cells.

Regulation of the intestinal barrier is closely associated with intestinal microbial metabolism. This study investigated the role of propionate, a major short-chain fatty acid produced by intestinal microorganisms, in the regulation of the tight junction (TJ) barrier in human intestinal Caco-2 cells. Propionate strengthened TJ barrier integrity, as indicated by decreased permeability to macromolecules and increased transepithelial electrical resistance in Caco-2 cells. DNA microarray analysis revealed that propionate upregulated endothelial cell-selective adhesion molecule (ESAM), a TJ-associated protein, without any increase in other TJ proteins. The upregulation of ESAM was confirmed using quantitative reverse transcription-PCR, immunoblotting, and immunofluorescence analyses. Luciferase promoter analysis demonstrated that propionate induced the transcriptional activation of ESAM. The effects of propionate were sensitive to nilotinib inhibition of NR2C2. Overexpression of human ESAM (hESAM) in canine kidney epithelial MDCK-II cells lowered the permeability to macromolecules in a manner similar to that of propionate-treated Caco-2 cells. hESAM overexpression facilitated calcium-induced assembly of the TJ complex in MDCK-II cells. Taken together, propionate strengthened the intestinal TJ barrier by increasing ESAM levels in Caco-2 cells.

Propionate and Dietary Fermentable Fibers Upregulate Intestinal Heat Shock protein70 in Intestinal Caco-2 Cells and Mouse Colon.

Short-chain fatty acids (SCFAs), including propionate, are major metabolites of intestinal microorganisms and play an essential role in regulating intestinal epithelial integrity. Heat shock proteins (HSPs) promote cellular homeostasis under physiological and stressed conditions. This study aimed to investigate the regulation of intestinal HSP70 by propionate in human intestinal Caco-2 cells and the colon of fermentable dietary fiber (DF)-fed mice and germ-free mice. The results showed that propionate increased Hspa1a (HSP70 mRNA) level in Caco-2 cells, upregulated HSP70 protein, and phosphorylation of heat shock factor 1; however, the latter two were reduced by mitogen-activated protein kinases and the mechanistic target of rapamycin inhibitors. Feeding fermentable DFs, such as guar gum (GG) and partially hydrolyzed GG, increased both cecal SCFAs and colonic HSP70 expression, both of which were reduced in germ-free mice than in specific-pathogen-free mice. Collectively, the propionate-induced HSP70 expression was shown to be possibly involved in intestinal homeostasis.