Abstract
primary HSC by transfection of complementary LNA sequences or miR125b mimics, respectively. For induction of experimental fibrosis, bile-duct ligation was performed. Furthermore miRNA expression level were studied in 84 liver biopsies representing different stages of fibrosis. Results: Microarray analyses revealed 42 differentially expressed miRNAs during in vitro induced myofibroblastic differentiation of primary HSC. miR-22, miR-31, miR-125b and miR-143 were more than 2-fold upregulated. miR-126 was downregulated in myofibroblastic HSC and one miRNA, not yet annotated in miRBase, was more than 3-fold reduced. Real-time PCR confirmed the expression profile shown by microarray analyses. During fibrogenesis in rat and in man, miR-143 did not alter and miR-22 and miR-125b was moderately repressed (p< 0.05). Whereas miR-125b was highly upregulated during myofibroblastic transition, its identified target gene, the promoting factor of pluripotency, Lin28, showed prominent downregulation. miR-125b effects on HSC pluripotency were suggested and targeting of the Lin28-3′UTR-sequence was proven by a miR-125b reporter construct in primary HSC. Conclusion: miRNA are suggested to be involved in myofibroblastic activation of HSC especiallly miR-125b seems to play a crucial role by regulation of the stem-cell specific factor, Lin28, which is also subject of further studies.
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