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Improving RhoA-mediated intestinal epithelial permeability by continuous blood purification in patients with severe
Qing Shen1, Hua Gan, Mengxue Yang
1Department of Nephrology, First Affiliated Hospital of Chongqing Medical University, Chongqing - China.
Insights
Continuous blood purification (CBP) reduces intestinal permeability in severe acute pancreatitis (SAP) by improving tight junction proteins. This effect is linked to decreased RhoA mRNA and tumor necrosis factor-alpha (TNF-α) levels.
Area of Science:
- Gastroenterology
- Critical Care Medicine
- Renal Medicine
Background:
- Intestinal mucosal barrier dysfunction increases intestinal permeability, potentially impacting severe acute pancreatitis (SAP) pathophysiology.
- Continuous blood purification (CBP) shows promise in improving SAP prognosis, but its effects on intestinal epithelial permeability are understudied.
Purpose of the Study:
- To investigate the therapeutic effects of CBP on intestinal epithelial permeability in patients with SAP.
Main Methods:
- Caco-2 intestinal epithelial cells were exposed to serum from SAP patients undergoing CBP.
- Assessed changes in cell permeability, tight junction proteins (occludin, ZO-1), RhoA mRNA, and serum tumor necrosis factor-alpha (TNF-α).
Main Results:
- Before CBP, increased intestinal permeability, decreased tight junction proteins, and elevated RhoA mRNA and TNF-α were observed.
- After CBP, intestinal permeability decreased, tight junction proteins increased, and RhoA mRNA and TNF-α levels were reduced.
Conclusions:
- CBP reduces intestinal epithelial permeability in SAP by enhancing occludin and ZO-1 protein levels.
- The beneficial effects of CBP may involve down-regulating RhoA mRNA expression and potentially removing TNF-α.
Background:
Early dysfunction of the intestinal mucosal barrier contributes to increasing intestinal permeability. It may play an important role in the pathophysiology of severe acute pancreatitis (SAP). A rising number of clinical data have showed that continuous blood purification (CBP) may improve the prognosis of SAP. However, the therapeutic effects of CBP on intestinal epithelial permeability have been rarely reported.
Methods:
Intestinal epithelial monolayer (Caco-2) was incubated with serum samples collected at specific time points from SAP patients during CBP. Changes in intestinal epithelial monolayer permeability and configuration, and levels of cellular tight junction structural proteins including occludin and ZO-1, and RhoA mRNA expression level were recorded, respectively. In addition, serum tumor necrosis factor-alpha (TNF-α) levels at specific time points during CBP were determined.
Results:
Before CBP initiation, intestinal epithelial permeability was increased and tight junction structural protein level was decreased and reorganized, but RhoA mRNA expression and serum TNF-α were increased. However, after CBP treatment, intestinal epithelial permeability was reduced and tight junction protein levels were increased, with reorganization attenuated. Meanwhile, RhoA mRNA expression and serum TNF-α level was decreased.
Conclusions:
After CBP treatment, intestinal epithelial permeability was reduced by increasing occludin and ZO-1 protein level and attenuating reorganization. This beneficial effect of CBP on intestinal epithelial permeability is associated with down-regulation of RhoA mRNA expression, and it may be related to the removal of TNF-α by CBP.
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