CircRbfox1 Contributes to Colonic Hypersensitivity in Rats With Diabetes by Altering HuC Subcellular Localization to Regulate RBFOX1 Expression

CircRbfox1通过改变HuC亚细胞定位来调节RBFOX1表达,从而导致糖尿病大鼠结肠高敏感性。

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Abstract

AIMS: The purpose of this study was to explore the molecular mechanism of circRNA mediated colonic hypersensitivity in rats with diabetes. METHODS: Intraperitoneal injection of streptozocin female rats was used to induce Type 1 Diabetes Mellitus. A combination of molecular biology and behavioral approaches was used to investigate the role of circRbfox1 in the pathogenesis of colonic hypersensitivity in diabetic rats. RESULTS: A new circular RNA-Rbfox1, derived from the host gene encoding RNA-Binding Protein Fox1, as a mechanism of visceral pain is identified. We confirmed that circRbfox1 remarkably upregulated in T13-L2 dorsal root ganglions in rats with diabetes, and could interact with the RNA-binding protein HuC to promote its transition from the cytosol into the nucleus to promote the translation level of RBFOX1. In addition, the increased expression of Rbfox1 could further promote colonic hypersensitivity in diabetic rats by regulating the expression of Cav1.3. CONCLUSIONS: We conclude that circRbfox1 serves as pain regulator in diabetic colonic hypersensitivity and provides a potential therapeutic target in clinic.

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