CCN1 is a matricellular protein that activates many genes related to wound healing and tissue remodeling in fibroblasts, but its effect on epithelial cells remains unclear. This study examined the role of CCN1 in epithelial wound healing using rat gastric epithelial cells and rat stomach ulcer as in vitro and in vivo models, respectively. We found that CCN1 expression is highly upregulated in the epithelial cells adjacent to a wound and remains high until the wound is healed. Upregulation of CCN1 activates a transient epithelial-mesenchymal transition in the epithelial cells at the migrating front and drives wound closure. Once the wound is healed, these epithelial cells and their progeny can resume their original epithelial phenotype. We also found that CCN1-induced E-cadherin loss is not due to transcriptional regulation but rather protein degradation due to the collapse of adherens junctions, which is contributed by b-catenin translocation. CCN1-activated integrin-linked kinase mediates this process. Finally, our in vivo study showed that locally neutralizing CCN1 drastically impairs wound closure, whereas local injection of recombinant CCN1 protein induces expression of vimentin and smooth muscle a-actin in normal gastric mucosal epithelial cells and accelerates re-epithelialization during ulcer healing. In conclusion, our study indicates that CCN1 can induce reversible epithelial-mesenchymal transition, and this feature may have great value for clinical wound healing.

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Serum response factor (SRF) is a transcription factor that regulates many genes involved in cellular activities such as proliferation, migration, differentiation, angiogenesis, and apoptosis. Although it has only been known for about two decades, SRF has been studied extensively. To date, over a thousand SRF studies have been published, but it still remains a hot topic. Due to its critical role in mesoderm-derived tissues, most of the SRF studies focused on muscle structure/function, cardiovascular development/maintenance, and smooth muscle generation/repair. Recently, SRF has received more attention in the digestive field and several important discoveries have been made. This review will summarize what we have learned about SRF in the gastrointestinal tract and provide insights into possible future directions in this area.

The Akt pathway is very important in both development and cancer. Here we show that expression of Casein kinase I epsilon (CKIε) causes up-regulation of the Akt pathway despite normal protein expression of the pathway inhibitor Phosphata and tensin homologue deleted on chromosome ten (PTEN). Conversly we show that a CKIε/δ-specific inhibitor can inhibit Akt phosphorylation at both Thr308 and Ser473 and drastically reduce phosphorylation of the Akt target Glycogen Synthase Kinase 3β (GSK3β). These conclusions were confirmed between MCF7 cells transiently transfected with CKIε and Hs578T cells which already express endogenous CKIε. The results suggest that CKIε is a new positive regulator of the Akt pathway. Here we propose that, rather than inhibiting PTEN function, CKIε positively regulates Akt possibly by inhibiting Protein Phosphatase 2A (PP2A).

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