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Importance of inhibitor of DNA binding/differentiation 2 in hepatic stellate cell differentiation and proliferation
Author(s) -
Tajima Kunihiko,
Terai Shuji,
Takami Taro,
Kawaguchi Kotaro,
Okita Kiwamu,
Sakaida Isao
Publication year - 2007
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/j.1872-034x.2007.00089.x
Subject(s) - hepatic stellate cell , cellular differentiation , biology , myod , transcription factor , microbiology and biotechnology , cell growth , myofibroblast , myocyte , fibrosis , myogenesis , gene , genetics , medicine , endocrinology
Background/Aim: In liver fibrosis, activated hepatic stellate cells (HSC) are transformed into myofibroblasts. Helix‐loop‐helix (HLH) transcriptional factors such as MyoD regulate the differentiation of myocytes, and the inhibitor of DNA binding/differentiation (Id) family comprises dominant negative HLH transcriptional regulators that inhibit differentiation and promote cell proliferation. In the present study, we investigated how the Id family proteins regulate HSC. Methods: In primary rat HSC, inhibitor of DNA binding/differentiation (Id)2 and α‐smooth muscle actin (α‐SMA) mRNA expression increased 4 days after isolation. Next we established Id2 expressing HSC (HSC‐T6‐Id2‐green fluorescent protein (GFP)) using HSC‐T6 cells with retrovirus that expressed GFP‐tagged Id2. Results: HSC‐T6‐Id2‐GFP increased cell proliferation with cyclin D1 expression. In contrast, α‐SMA expression wassuppressed. Real‐time reverse transcription–polymerase chain reaction analysis showed Id2 induction significantly suppressed α‐SMA, collagen‐1, matrix metalloproteinase (MMP)‐2, and MMP‐9 mRNA ( P < 0.05) but had no effect on tissue inhibitor of metalloproteinase or transforming growth factor‐β1 levels. Conclusion: These findings suggest Id2, an HLH transcriptional regulator, plays an important regulatory role in the proliferation and differentiation of HSC.