1. FGF13 enhances the function of TRPV1 by stabilizing microtubules and regulates acute and chronic itch.
- Author
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Dong ZS, Zhang XR, Xue DZ, Liu JH, Yi F, Zhang YY, Xian FY, Qiao RY, Liu BY, Zhang HL, and Wang C
- Subjects
- Animals, Humans, Male, Mice, Ganglia, Spinal metabolism, HEK293 Cells, Mice, Inbred C57BL, TRPA1 Cation Channel metabolism, TRPA1 Cation Channel genetics, Fibroblast Growth Factors metabolism, Fibroblast Growth Factors genetics, Mice, Knockout, Microtubules metabolism, Pruritus metabolism, Pruritus genetics, TRPV Cation Channels metabolism, TRPV Cation Channels genetics
- Abstract
Itching is an aversive somatosensation that triggers the desire to scratch. Transient receptor potential (TRP) channel proteins are key players in acute and chronic itch. However, whether the modulatory effect of fibroblast growth factor 13 (FGF13) on acute and chronic itch is associated with TRP channel proteins is unclear. Here, we demonstrated that conditional knockout of Fgf13 in dorsal root ganglion neurons induced significant impairment in scratching behaviors in response to acute histamine-dependent and chronic dry skin itch models. Furthermore, FGF13 selectively regulated the function of the TRPV1, but not the TRPA1 channel on Ca
2+ imaging and electrophysiological recordings, as demonstrated by a significant reduction in neuronal excitability and current density induced by TRPV1 channel activation, whereas TRPA1 channel activation had no effect. Changes in channel currents were also verified in HEK cell lines. Subsequently, we observed that selective modulation of TRPV1 by FGF13 required its microtubule-stabilizing effect. Furthermore, in FGF13 knockout mice, only the overexpression of FGF13 with a tubulin-binding domain could rescue TRP channel function and the impaired itch behavior. Our findings reveal a novel mechanism by which FGF13 is involved in TRPV1-dependent itch transduction and provide valuable clues for alleviating pathological itch syndrome., (© 2024 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)- Published
- 2024
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