Functional relevance of activin A in the intestinal epithelium

Background: Activin A modulates inflammation and repair in various tissues. The aim of this study was to characterize the effects of activin A on intestinal epithelial cell function and to evaluate a potential role in intestinal epithelial wound repair and inflammation. Methods: The expression of activin A and its receptors ActRI and ActRII in intestinal epithelial IEC-6 cells and in tissues from IBD patients and noninflamed controls was evaluated using RT-PCR and immunohistochemistry. Functional effects of activin A on intestinal epithelial cell migration and proliferation were assessed using an in vitro wounding model and colorimetric MTT assays. Results: Expression of the activin betaA subunit and the activin receptors ActRI and ActRII in IEC-6 cells was demonstrated using RT-PCR. Activin A (50 ng/ml) caused a significant, on average 2.8-fold enhancement of epithelial cell migration and a significant on average 4.1-fold inhibition of IEC-6 cell proliferation. Expression of ActRI and ActRII was observed in all intestinal tissues from patients with IBD and in all controls. In contrast, no expression of the activin betaA-subunit was observed in controls, while betaA expression was found in intestinal tissues from IBD patients. Conclusions: Activin A may play an important role in the modulation of intestinal epithelial cell function, thus providing a new approach to modulate intestinal wound repair.