Shin Ji Hyun, Kim Pan Soo, Kim Eun Sung, Park So Jung, Jo Yoon Kyung, Hwang Jung Jin, Park Tae Joo, Chang Jong Wook, Seo Jin-Ho, Cho Dong-Hyung
Graduate School of East-West Medical Science, Kyung Hee University, Yongin, Gyeonggi 446-701, South Korea.
Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, South Korea.
Biochem Biophys Res Commun. 2015 May 1;460(2):428-33. doi: 10.1016/j.bbrc.2015.03.050. Epub 2015 Mar 18.
Previously, we showed that BIX-01294 treatment strongly activates autophagy. Although, the interplay between autophagy and ciliogenesis has been suggested, the role of autophagy in ciliogenesis is controversial and largely unknown. In this study, we investigated the effects of autophagy induced by BIX-01294 on the formation of primary cilia in human retinal pigmented epithelial (RPE) cells. Treatment of RPE cells with BIX-01294 caused strong elongation of the primary cilium and increased the number of ciliated cells, as well as autophagy activation. The elongated cilia in serum starved cultured cells were gradually decreased by re-feeding the cells with normal growth medium. However, the disassembly of cilia was blocked in the BIX-01294-treated cells. In addition, both genetic and chemical inhibition of autophagy suppressed BIX-01294-mediated ciliogenesis in RPE cells. Taken together, these results suggest that autophagy induced by BIX-01294 positively regulates the elongation of primary cilium.
此前,我们发现BIX-01294处理可强烈激活自噬。尽管已有研究表明自噬与纤毛发生之间存在相互作用,但自噬在纤毛发生中的作用仍存在争议且很大程度上未知。在本研究中,我们调查了BIX-01294诱导的自噬对人视网膜色素上皮(RPE)细胞中初级纤毛形成的影响。用BIX-01294处理RPE细胞会导致初级纤毛强烈伸长,增加纤毛细胞数量,并激活自噬。通过用正常生长培养基重新培养血清饥饿的培养细胞,可使伸长的纤毛逐渐减少。然而,在BIX-01294处理的细胞中,纤毛的解体受到阻碍。此外,自噬的基因抑制和化学抑制均抑制了BIX-01294介导的RPE细胞纤毛发生。综上所述,这些结果表明BIX-01294诱导的自噬正向调节初级纤毛的伸长。