Specific Expression and Regulation of the New Melanoma Inhibitory Activity-related Gene MIA2 in Hepatocytes

Abstract

The novel human gene MIA2 encoding a melanoma inhibitory activity (MIA) homologous protein was identified by a GenBank TM search. MIA2, together with MIA, OTOR, and TANGO, belongs to the novel MIA gene family sharing important structural features, significant homology at both the nucleotide and protein levels, and similar genomic organization. In situ hybridization, reverse transcriptase-PCR, and Northern blots presented a highly tissue-specific MIA2 expression pattern in the liver. Promoter studies analyzing transcriptional regulation of MIA2 revealed an HNF-1-binding site at position ؊236 controlling hepatocyte-specific expression. Mutation of the site led to a complete loss of promoter activity in HepG2 cell. Further sites detected in the MIA2 promoter were consensus binding sites for SMAD and STAT3, Consistently, stimulation of MIA2 mRNA expression occurred by treatment with interleukin-6, transforming growth factor-␤, and conditioned medium from activated hepatic stellate cells. In accordance with these results, MIA2 mRNA was found to be increased in liver tissue of patients with chronic hepatitis C infection compared with controls. MIA2 mRNA levels were significantly higher in patients with severe fibrosis or inflammation than in patients with less severe fibrosis or inflammation. In summary our data indicate that MIA2 represents a potential novel acute phase protein and MIA2 expression responds to liver damage. The increased transcription in more severe chronic liver disease suggests that MIA2 may serve as a marker of hepatic disease activity and severity.

Fusarium mycotoxin-contaminated wheat containing deoxynivalenol alters the gene expression in the liver and the jejunum of broilers

“…MIA2 expression is regulated by IL-6 and transforming growth factor-beta, which increased the expression level of MIA2 in human hepatocytes and in HepG2 cells (Bosserhoff et al, 2003). The downregulation of MIA2 in the liver and the jejunum may indicate a reduced amount of IL-6 in the liver cells of broilers.…”

Hepatocellular carcinoma cells surviving doxorubicin treatment exhibit increased migratory potential and resistance to doxorubicin re-treatment in�vitro

“…no. HB-8064; American Type Culture Collection, Manassas, VA, USA) cell lines were cultured as described previously (23). Briefly, cells were maintained in high-glucose Dulbecco's modified Eagle's medium (DMEM) (Sigma-Aldrich, Taufkirchen, Germany) supplemented with penicillin (400 U/ml), streptomycin (50 µg/ml), L-glutamine (300 µg/ml) and 10% fetal calf serum (FCS; Sigma-Aldrich; Merck Millipore, Deisenhofen, Germany) and were passaged at a 1:5 ratio every 3 days.…”

Increased expression of c-Jun in nonalcoholic fatty liver disease

“…28,29 Under the same conditions, cells were stimulated with indicated concentrations of the FFA palmitic acid for 24 h using a specifically prepared palmitic acid/bovine serum albumin (BSA) stock solution. Preparation of the palmitic acid/BSA stock solution was carried out as described previously.…”