Effects of the lignan compound (+)-Guaiacin on hair cell survival by activating Wnt/β-Catenin signaling in mouse cochlea

Abstract

Wnt/β-Catenin signaling is required for the development and differentiation of cochlear hair cells. Total of 80 natural compounds derived from the FDA-approved Drug Library of Selleck were screened by T-cell factor Reporter Plasmid (TOP)-Flash assay to identify the activation of Wnt/β-Catenin signaling. The mouse cochlear hair cells (HEI-OC1) were treated with cisplatin with or without Guaiacin, and the relative expression of β-Catenin and TRIM33 were detected by qRT-PCR and Western blots. The viability of HEI-OC1 was assayed by MTT method, and mouse cochlear cultures were utilized to detect the Ex vivo survival of cochlear hair cells. Guaiacin was testified to have the most vigorous ability to promote Wnt/β-Catenin signaling among 80 compounds detected, and it can also improve the β-Catenin signaling in mouse cochlear hair cells with up-regulated β-Catenin protein expression, unchanged β-Catenin mRNA expression, and down-regulated TRIM33 expression. Guaiacin increased the viability of HEI-OC1 cells cultured with or without cisplatin, and such a protective effect was also testified in mouse cochlear cultures. Our data indicate that Guaiacin could increase Wnt/β-Catenin signaling by regulating TRIM33/β-Catenin axis, which contributes to the improved survival of cochlear hair cells.