Lactobacillus casei LC01 Regulates Intestinal Epithelial Permeability through miR-144 Targeting of OCLN and ZO1

Abstract

Our previous report determined that miR-144 is a key regulator of intestinal epithelial permeability in irritable bowel syndrome with diarrhea (IBS-D) rats. Recent evidence has shown that lactobacilli play an important role in the relief of IBS-D symptoms. However, few studies have addressed the mechanisms by which microRNAs and lactobacilli exert their beneficial effects on intestinal epithelial permeability. Hence, to elucidate whether miRNAs and lactobacilli play roles in intestinal epithelial barrier regulation, we compared miRNA expression levels in intestinal epithelial cells (IECs) under Lactobacillus casei ( L. casei LC01) treatment. IECs and L. casei LC01 were co-cultured and then subjected to microRNA microarray assay. qRT-PCR, western blot and ELISA were used to detect the expression of occludin (OCLN) and zonula occludens 1 (ZO1/TJP1). The interaction between miRNAs and L. casei LC01 acting in IECs was investigated through transfection of RNA oligoribonucleotides and pcDNA 3.1 plasmid. The results are as follows: 1) L. casei LC01 decreased the expression of miR-144 and FD4 and promoted OCLN and ZO1 expression in IECs; 2) L. casei LC01 enhanced the barrier function of IECs via downregulation of miR-144 and upregulation of OCLN and ZO1; 3) Under L. casei LC01 treatment, OCLN and ZO1 overexpression could partially eliminate the promoting effect of miR-144 on intestinal permeability in IECs. Our results demonstrate that L. casei LC01 regulates intestinal permeability of IECs through miR-144 targeting of OCLN and ZO1. L. casei LC01 can be a possible therapeutic target for managing dysfunction of the intestinal epithelial barrier.

The beneficial effects of Lacticaseibacillus casei on the small intestine and colon of Swiss mice against the deleterious effects of 5-fluorouracil

“…Accordingly, the analysis of cell adhesion-related gene expression shows significant up-regulation of occludin and zonula occludens-1 (ZO-1), important tight junction proteins, in the intestine of the L. casei group. Our results are in agreement with previous studies, showing the role of lactobacilli on the intestinal epithelial barrier regulation (30,31).…”

Supplemental magnolol or honokiol attenuates adverse effects in broilers infected with Salmonella pullorum by modulating mucosal gene expression and the gut microbiota

“…Consistent with other reports, lactobacilli are dominant in the ileum at the genus level [ 39 , 40 ]. Several studies have repeatedly shown that lactobacilli , as the most important microbiota in animal intestines, have various biochemical functions, including in the protection of the integrity of the intestinal mucosal, the invasion of pathogens, and stimulation of the immune system [ 41 , 42 ]. Many probiotic strains of lactobacilli have been widely used in poultry production [ 43 ].…”

Dietary Palygorskite Clay-Adsorbed Nano-ZnO Supplementation Improves the Intestinal Barrier Function of Weanling Pigs

“…Tight junction proteins and mucins affect intestinal mucosal integrity ( 30 ). ZO1 is a tight junction protein that connects cells to form a barrier to protect the body from the contents of the intestine ( 31 ). The current study showed that dietary supplementation with 700 mg/kg PNZ could upregulate the gene expression of ZO1 better than ANT and NZO, which indicated that PNZ has a beneficial effect on barrier function and intestinal integrity.…”