title: Dixdc1 targets CyclinD1 and p21 via PI3K pathway activation to promote Schwann cell proliferation after sciatic nerve crush.
abstract: Dixdc1 (DIX domain containing-1), the mammalian homolog of Ccd1 (Coiled-coil-Dishevelled-Axin1), is a protein containing a coiled-coil domain and a Dishevelled-Axin (DIX) domain. As a novel component of the Wnt pathway, Dixdc1 has been reported to be able to promote neural progenitor proliferation and neuronal differentiation via Wnt/β-catenin signaling. But there still remains something unknown about Dixdc1 distribution and functions in the lesion and regeneration of the peripheral nervous system (PNS), so we tried to investigate dynamic changes of Dixdc1 expression in a rat sciatic nerve crush (SNC) model in this study. First of all, we detected SNC-induced increased levels of Dixdc1 in Schwann cells and interestingly identified parallel expression of PCNA (proliferation cell nuclear antigen) with Dixdc1. Besides, we observed up-regulated Dixdc1 during the process of TNF-α-induced Schwann cell proliferation. Also, we discovered that Dixdc1 could promote G1-S phase transition accompanied with the up-regulation of CyclinD1 and down-regulation of p21. More importantly, enhanced effects of Dixdc1 on cell proliferation were confirmed to be associated with PI3K activation. Not only blocking of the PI3K but Dixdc1 knockdown led to significantly decreased ability for proliferation, as well as down-regulation of CyclinD1 and up-regulation of p21. In summary, these data demonstrated that Dixdc1 might participate in Schwann cell proliferation by targeting CyclinD1 and p21 at least partially through the PI3K/AKT activation.
authors: Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, People's Republic of China.
authors: Weijie
authors: W
authors: Wu
authors: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong, 226001, Jiangsu Province, People's Republic of China.
authors: Qingqing
authors: Q
authors: Liu
authors: Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, People's Republic of China.
authors: Yuxi
authors: Y
authors: Liu
authors: Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, People's Republic of China.
authors: Zhaohui
authors: Z
authors: Yu
authors: Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, People's Republic of China. Electronic address: wyouhua1516@163.com.
authors: Youhua
authors: Y
authors: Wang
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism*; D009409:Nerve Crush; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000378:metabolism / Q000473:pathology*; D012584:Sciatic Nerve / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D008840:Microfilament Proteins; D034741:RNA, Small Interfering; D019938:Cyclin D1; D019869:Phosphatidylinositol 3-Kinases
keywords: Cell cycle; Cell proliferation; Dixdc1; PI3K; Schwann cell; Sciatic nerve crush