Effect of transient receptor potential vanilloid 4 agonist GSK1016790A on axonal regeneration

doi:10.12307/2022.574

Abstract

Abstract: BACKGROUND: The transient receptor potential vanilloid 4 (TRPV4) agonist GSK1016790A can activate TRPV4 protein and induce Ca2+ influx in a short time, while its expression remains unchanged. However, during culture, the decreased expression of TRPV4 on HeLa cell membrane surface was induced by GSK1016790A. Whether the phenomenon had an effect on neural regeneration is still not clear.
OBJECTIVE: To explore the effect of TRPV4 agonist GSK1016790A on axonal regeneration in different periods.
METHODS: The dorsal root ganglion cells of ICR mouse at 6-8 weeks were treated by collagenase and trypsin for cell culture. In the 2-hour group, the agonist GSK1016790A was added at the initial stage of culture and the cells were treated for 2 hours and the culture was continued for 3 days. The 3-day group was treated with the agonist GSK1016790A for 3 days. The blank control group did not undergo any treatment. The TRPV4 protein expression and axon regeneration related protein expression were examined by western blot assay. TUJ1 and TRPV4 immunofluorescence staining was performed simultaneously. Number of axon branches, length of axon regeneration, and number of cell survival were counted.
RESULTS AND CONCLUSION: (1) Compared with the blank control group, there was no significant difference in TRPV4 protein changes after GSK101 stimulated nerve cells for 2 hours (P > 0.05); while the expression of TRPV4 decreased significantly after nerve cells were stimulated for 3 days (P < 0.05). (2) Compared with the blank control group, after GSK1016790A stimulated nerve cells for 2 hours, there was no significant difference in the number of axon branches and axon length (P > 0.05); after stimulating nerve cells for 3 days, the number of axon bifurcations and axon length were increased significantly (P < 0.05). (3) Compared with the blank control group, there was no significant change in cell survival rate after GSK1016790A stimulated nerve cells for 2 hours or 3 days. (4) Compared with the blank control group, after GSK1016790A stimulated nerve cells for 3 days, the expression of PTEN decreased (P < 0.05), and the regeneration of nerve axons was significant. This process may be mediated by inhibiting the expression of PTEN protein.

Key words: transient receptor potential vanilloid 4, GSK1016790A, dorsal root ganglion, nerve regeneration, axon, PTEN protein

CLC Number:

Qin Xuzhen, Ma Jinjin, Li Meimei, Wang Xingran, Xie Jile, Saijilafu. Effect of transient receptor potential vanilloid 4 agonist GSK1016790A on axonal regeneration[J]. Chinese Journal of Tissue Engineering Research, 2022, 26(24): 3903-3907.

Figures/Tables 5

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