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World J Gastroenterol. Oct 28, 2008; 14(40): 6249-6253
Published online Oct 28, 2008. doi: 10.3748/wjg.14.6249
Midkine accumulated in nucleolus of HepG2 cells involved in rRNA transcription
Li-Cheng Dai, Jian-Zhong Shao, Li-Shan Min, Yong-Tao Xiao, Li-Xin Xiang, Zhi-Hong Ma
Li-Cheng Dai, Li-Shan Min, Zhi-Hong Ma, Huzhou key laboratory of Molecular Medicine, Huzhou Central Hospital, Huzhou 313000, Zhejiang Province, China
Yong-Tao Xiao, Li-Xin Xiang, Jian-Zhong Shao, College of Life Sciences, Zhejiang University, Hangzhou 310031, Zhejiang Province, China
Author contributions: Dai LC and Shao JZ contributed equally to this work; Dai LC and Shao JZ designed research; Min LS, Xiao YT and Ma ZH performed research; Xiang LX contributed new reagents/analytic tools; Dai LC, Shao JZ, Min LS, Xiao YT and Ma ZH analyzed data; Dai LC, Min LS and Xiao YT wrote the paper.
Supported by The Medical Science Research Foundation of Zhejiang Province, No. 2004A083
Correspondence to: Li-Cheng Dai, Professor, Huzhou key laboratory of Molecular Medicine, Huzhou Central Hospital, Huzhou 313000, China. dlc@hzhospital.com
Telephone: +86-572-2033020 Fax: +86-572-2033020
Received: July 11, 2008
Revised: September 19, 2008
Accepted: September 26, 2008
Published online: October 28, 2008
Abstract

AIM: To investigate the ultrastructural location of midkine (MK) in nucleolus and function corresponding to its location.

METHODS: To investigate the ultrastructural location of MK in nucleolus with immunoelectronic microscopy. To study the role that MK plays in ribosomal biogenesis by real-time PCR. The effect of MK on anti-apoptotic activity of HepG2 cells was studied with FITC-conjugated annexin V and propidium iodide PI double staining through FACS assay.

RESULTS: MK mainly localized in the granular component (GC), dense fibrillar component (DFC) and the border between the DFC and fibrillar center (FC). The production of 45S precursor rRNA level was decreased significantly in the presence of MK antisense oligonucleotide in the HepG2 cells. Furthermore, it was found that exogenous MK could protect HepG2 from apoptosis significantly.

CONCLUSION: MK was constitutively translocated to the nucleolus of HepG2 cells, where it accumulated and mostly distributed at DFC, GC components and at the region between FC and DFC, MK played an important role in rRNA transcription, ribosome biogenesis, and cell proliferation in HepG2 cells. MK might serve as a molecular target for therapeutic intervention of human carcinomas.

Keywords: 45S rRNA; Anti-apoptosis; Proliferation; Midkine