Importance of inhibitor of DNA binding/differentiation 2 in hepatic stellate cell differentiation and proliferation

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 (ld)2 and alpha-smooth muscle actin (alpha-SIVIA) mRNA expression increased 4 days after isolation. Next we established ld2 expressing HSC (HSC-T6-Id2-green fluorescent protein (GFP)) using HSC-T6 cells with retrovirus that expressed GFP-tagged ld2. Results: HSC-T6-Id2-GFP increased cell proliferation with cyclin D1 expression. In contrast, alpha-SMA expression was suppressed. Real-time reverse transcri ption-polym erase chain reaction analysis showed ld2 induction significantly suppressed alpha-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-beta 1 levels. Conclusion: These findings suggest ld2, an HLH transcriptional regulator, plays an important regulatory role in the proliferation and differentiation of HSC.