MMP9 is involved in HO-1-mediated upregulation of apical junctional complex in Caco-2 cells under oxygen-glucose deprivation

MMP9 参与 HO-1 介导的 Caco-2 细胞在氧-糖缺乏条件下顶端连接复合物的上调

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作者:Yongqu Lu, Jie An, Yulin Liu, Lehao Ren, Li Zhang

Abstract

Ischemia reperfusion injury is a critical factor in the recovery process after intestine trauma and the functional restoration of intestinal reconstruction. This study was the first to explore the expression of apical junctional complex (AJC) induced by heme oxygenase-1 (HO-1) in Caco-2 cells in oxygen-glucose deprivation (OGD) models. Here we showed that HO-1 was upregulated after OGD. Notably, activation of HO-1 largely enhanced the expression of AJC proteins including Claudin-4, E-cadherin and β-catenin in Caco-2 cells, but decreased the expression of matrix metalloproteinase 9 (MMP9). Knockdown of HO-1 attenuated the OGD-induced overexpression of AJC proteins but promoted the expression of MMP9. Interestingly, inhibition of MMP9 further enhanced AJC expression. These results suggest that HO-1 is involved in OGD-evoked upregulation of AJC proteins, which is partly mediated by MMP9 pathway. High expression of HO-1 may play an important role in the pathophysiological process of ischemia reperfusion injury and has potential clinical value for the treatment of intestine related diseases.

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