Intestinal Mucosal Barrier Is Injured by BMP24 via Activation of NF- κ B Signals after Ischemic Reperfusion

Abstract EN

Intestinal ischemic reperfusion (I/R) can cause dysfunction of the intestinal mucosal barrier; however, the mechanism of the intestinal mucosal barrier dysfunction caused by I/R remains unclear.

In this study, using intestinal epithelial cells under anaerobic cultivation and an in vivo rat intestinal I/R model, we found that hypoxia and I/R increased the expression of BMP2/4 and upregulated BMP type Ia receptor and BMP type II receptor expression.

We also found that exogenous BMP2/4 can activate the ERK and AKT signaling pathways in rat small intestine (IEC-6) cells, thereby activating NF- κ B signaling, which leads to increased levels of inflammatory factors, such as TNF- α and IL-6.

Furthermore, recombinant BMP2/4 decreased the expression of the tight junction protein occludin via the activation of the NF- κ B pathway; these effects were abolished by treatment with the BMP-specific antagonist noggin or the NF- κ B inhibitor pyrrolidine dithiocarbamate (PDTC).

All these factors can destroy the intestinal mucosal barrier, thereby leading to weaker barrier function.

On the basis of these data, we conclude that BMP2/4 may act as the pathogenic basis for intestinal mucosal barrier dysfunction when the intestines suffer an I/R injury.

Our results provide background for the development pharmacologic interventions in the management of I/R injury.