TRPC1‐mediated Ca2+ signaling enhances intestinal epithelial restitution by increasing α4 association with PP2Ac after wounding
| Autor: | Hee Kyoung Chung, Navneeta Rathor, Jaladanki N. Rao, Jian-Ying Wang, Shelley R. Wang, Jia-Le Song |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
cell migration
epithelial restitution TRPC1 Physiology Protein subunit polyamines mucosal injury 030204 cardiovascular system & hematology IEC‐6 cells Ornithine decarboxylase Cell Line 03 medical and health sciences Transient receptor potential channel 0302 clinical medicine Cell Movement Physiology (medical) QP1-981 Gene silencing ornithine decarboxylase Animals Calcium Signaling Protein Phosphatase 2 Adaptor Proteins Signal Transducing TRPC Cation Channels Wound Healing Chemistry Cell migration Protein phosphatase 2 Transfection Original Articles Cell biology Rats Enterocytes Original Article 030217 neurology & neurosurgery Molecular Chaperones |
| Zdroj: | Physiological Reports Physiological Reports, Vol 9, Iss 9, Pp n/a-n/a (2021) |
| ISSN: | 2051-817X |
| Popis: | Gut epithelial restitution after superficial wounding is an important repair modality regulated by numerous factors including Ca2+ signaling and cellular polyamines. Transient receptor potential canonical‐1 (TRPC1) functions as a store‐operated Ca2+ channel in intestinal epithelial cells (IECs) and its activation increases epithelial restitution by inducing Ca2+ influx after acute injury. α4 is a multiple functional protein and implicated in many aspects of cell functions by modulating protein phosphatase 2A (PP2A) stability and activity. Here we show that the clonal populations of IECs stably expressing TRPC1 (IEC‐TRPC1) exhibited increased levels of α4 and PP2A catalytic subunit (PP2Ac) and that TRPC1 promoted intestinal epithelial restitution by increasing α4/PP2Ac association. The levels of α4 and PP2Ac proteins increased significantly in stable IEC‐TRPC1 cells and this induction in α4/PP2Ac complexes was accompanied by an increase in IEC migration after wounding. α4 silencing by transfection with siRNA targeting α4 (siα4) or PP2Ac silencing destabilized α4/PP2Ac complexes in stable IEC‐TRPC1 cells and repressed cell migration over the wounded area. Increasing the levels of cellular polyamines by stable transfection with the Odc gene stimulated α4 and PP2Ac expression and enhanced their association, thus also promoting epithelial restitution after wounding. In contrast, depletion of cellular polyamines by treatment with α‐difluoromethylornithine reduced α4/PP2Ac complexes and repressed cell migration. Ectopic overexpression of α4 partially rescued rapid epithelial repair in polyamine‐deficient cells. These results indicate that activation of TRPC1‐mediated Ca2+ signaling enhances cell migration primarily by increasing α4/PP2Ac associations after wounding and this pathway is tightly regulated by cellular polyamines. |
| Databáze: | OpenAIRE |
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