Spatiotemporal expression of HMGB2 regulates cell proliferation and hepatocyte size during liver regeneration.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

HMGB2 Protein*/genetics ; HMGB2 Protein*/metabolism ; Liver Regeneration*/physiology; Animals ; Cell Proliferation ; Chromatin/metabolism ; Hepatectomy ; Hepatocytes/metabolism ; Liver/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Transcription Factors/metabolism

Liver regeneration is an extraordinarily complex process involving a variety of factors; however, the role of chromatin protein in hepatocyte proliferation is largely unknown. In this study, we investigated the functional role of high-mobility group box 2 (HMGB2), a chromatin protein in liver regeneration using wild-type and HMGB2-knockout (KO) mice. Liver tissues were sampled after 70% partial hepatectomy (PHx), and analyzed by immunohistochemistry, western blotting and flow cytometry using various markers of cell proliferation. In WT mice, hepatocyte proliferation was strongly correlated with the spatiotemporal expression of HMGB2; however, cell proliferation was significantly delayed in hepatocytes of HMGB2-KO mice. Quantitative PCR demonstrated that cyclin D1 and cyclin B1 mRNAs were significantly decreased in HMGB2-KO mice livers. Interestingly, hepatocyte size was significantly larger in HMGB2-KO mice at 36-72 h after PHx, and these results suggest that hepatocyte hypertrophy appeared in parallel with delayed cell proliferation. In vitro experiments demonstrated that cell proliferation was significantly decreased in HMGB2-KO cells. A significant delay in cell proliferation was also found in HMGB2-siRNA transfected cells. In summary, spatiotemporal expression of HMGB2 is important for regulation of hepatocyte proliferation and cell size during liver regeneration.
(© 2022. The Author(s).)

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0 (Chromatin)
0 (HMGB2 Protein)
0 (Transcription Factors)

Date Created: 20220713 Date Completed: 20220715 Latest Revision: 20220921

20221213

PMC9279446

10.1038/s41598-022-16258-4

35831365