Xylobiose treatment strengthens intestinal barrier function by regulating claudin 2 and heat shock protein 27 expression in human Caco‐2 cells

Abstract

BACKGROUNDXylobiose, a non‐digestible disaccharide, largely contributes to the beneficial physiological effects of xylooligosaccharides. However, there is insufficient evidence to assess the direct effect of xylobiose on intestinal barrier function. Here, we investigated the intestinal barrier function in human intestinal Caco‐2 cells treated with xylobiose.RESULTSIn total, 283 genes were upregulated and 256 genes were downregulated in xylobiose‐treated Caco‐2 cells relative to the controls. We focused on genes related to intestinal barrier function, such as tight junction (TJ) and heat shock protein (HSP). Xylobiose decreased the expression of the TJ gene Claudin 2 (CLDN2) and increased the expression of the cytoprotective HSP genes HSPB1 and HSPA1A, which encode HSP27 and HSP70, respectively. Immunoblot analysis confirmed that xylobiose suppressed CLDN2 expression and enhanced HSP27 and HSP70 expression. A quantitative reverse transcription‐PCR and promoter assays indicated that xylobiose post‐transcriptionally regulated CLDN2 and HSPB1 levels. Additionally, selective inhibition of phosphatidyl‐3‐inositol kinase (PI3K) inhibited xylobiose‐mediated CLDN2 expression, whereas HSP27 expression induced by xylobiose was sensitive to the inhibition of PI3K, mitogen‐activated protein kinase kinase and Src.CONCLUSIONThe results of the present study reveal that xylobiose suppresses CLDN2 and increases HSP27 expression in intestinal Caco‐2 cells via post‐transcriptional regulation, potentially strengthening intestinal barrier integrity; however, these effects seem to occur via different signaling pathways. Our findings may help to assess the physiological role of xylobiose. © 2023 Society of Chemical Industry.

Identification of claudin-2 as a promising biomarker for early diagnosis of pre-diabetes

“…Research on CLDN2 has primarily focused on gastrointestinal diseases, due to its role as a member of the tight junction protein family, prompting extensive investigation into its role about the intestinal barrier ( Beggs et al, 2023 ; Ganapathy et al, 2023 ; Rini et al, 2023 ). Numerous studies have progressively affirmed its association with inflammatory bowel diseases ( Raju et al, 2020 ; Ahmad et al, 2023 ; Alghamdi and Al-Zahrani, 2023 ).…”