Primary cilium is a cellular antenna, signalling as a sensory organelle. Numerous pathological manifestation is associated with change of its length. Although the interaction between autophagy and primary cilia has been suggested, the role of autophagy in primary cilia length is largely unknown. In this study the primary cilia were immunostained and observed by using confocal fluorescence microscopy, and we found that
silibinin, a natural
flavonoid, shortened the length of primary cilia, meanwhile it also induced autophagy in 3T3-L1 cells. This study was designed to investigate the significance of
silibinin-induced autophagy in primary ciliary structure in confluent mouse embryo fibroblast 3T3-L1 cells. Either blocking the autophagic flux with pre-treatment with the autophagy inhibitor,
3-methyladenine (3-MA), or transfection of
siRNA targeting LC3 inhibited the reduction of cilia length caused by
silibinin exposure. Autophagy induced by
silibinin decreased expressions of the cilia-associated
proteins, such as IFT88, KIF3a and Ac-
tubulin, while 3-MA restored it, indicating that autophagy induced by
silibinin led to a reduction of primary cilia length.
Histone deacetylase 6 (HDAC6), which was suggested as a mediator of autophagy, was up-regulated by
silibinin in a time-dependent manner. In addition, 3T3-L1 cells treated with
siRNA against HDAC6 had a reduced autophagic level and were protected from
silibinin-induced cilia shortening. Taken together, we conclude that the HDAC6-mediated autophagy negatively regulates primary cilia length during
silibinin treatment and has the potential to serve as a therapeutic target for primary cilia-associated
ciliopathies. These findings thus provide new information about the potential link between autophagy and primary cilia.