Restricted expression of homeobox genes distinguishes fetal from adult human smooth muscle cells
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Authors: Miano, JM; Firulli, AB; Olson, EN; Hara, P; Giachelli, CM; Schwartz, SM
Abstract
Smooth muscle cell plasticity is considered a prerequisite for atherosclerosis and restenosis following angioplasty and bypass surgery, Identification of transcription factors that specify one smooth muscle cell phenotype over another therefore may be of major importance in understanding the molecular basis of these vascular disorders, Homeobox genes exemplify one class of transcription factors that could govern smooth muscle cell phenotypic diversity, Accordingly, we screened adult and fetal human smooth muscle cell cDNA libraries with a degenerate oligonucleotide corresponding to a highly conserved region of the homeodomain with the idea that homeobox genes, if present, would display a smooth muscle cell phenotype-dependent pattern of expression, No homeobox genes were detected in the adult human smooth muscle cell library; however, five nonparalogous homeobox genes were uncovered from the fetal library (HoxA5, HoxA11, HoxB1, HoxB7, and HoxC9). Northern blotting of adult and fetal tissues revealed low and restricted expression of all five homeobox genes. No significant differences in transcripts of HoxA5, HoxA11, and HoxB1 were detected between adult or fetal human smooth muscle cells in culture, HoxB7 and HoxC9, however, showed preferential mRNA expression in fetal human smooth muscle cells that appeared to correlate with the age of the donor, This phenotype-dependent expression of homeobox genes was also noted in rat pup versus adult smooth muscle cells, While similar differences in gene expression have been reported between subsets of smooth muscle cells from rat vessels of different-aged animals or clones of rat smooth muscle, our findings represent a demonstration of a transcription factor distinguishing two human smooth muscle cell phenotypes.
Cadmium exposure induces expression of the HOXB8 gene in COS-7 cells
TOXICOLOGY IN VITRO
Authors: Nakagawa, Kanako; Lee, Myeong Jin; Sasaki, Naoko; Hayashi, Chiyo; Nishio, Hisahide
Abstract
Cadmium (Cd) is a serious toxic metal. which is classified as a possible human carcinogen. We assessed the effects of CA on the expression levels of homeobox genes, which are associated with carcinogenesis. Among 6 homeobox genes examined in this study, only HOXB8 exhibited increased mRNA expression in COS-7 cells treated with 10 mu M CdCl2. Semiquantitative reverse transcription-polymerase chain reaction analysis revealed that the HOXB8 mRNA level was increased by a maximum of 5.4-fold after 6 h of Cd exposure. The levels of HOXA7, A9, C4, C9 and C10 mRNAs decreased from 0.1 to 0.3-fold. Silencing of HOXB8 mRNA expression using a siRNA increased HOXC9 and C10 mRNA expression levels by 6.6- and 1.9-fold, respectively. These results suggest that HOXB8 upregulation is associated with suppression of HOXC9 and C10, and that decreased expression of HOXC9 and C10 after Cd exposure is partly due to HCXB8 induction. In conclusion, Cd disrupts the HOX network. Comprehensive analyses of all the HOX gene expression levels in the presence of Cd may afford clues toward understanding Cd-induced carcinogenesis and teratogenesis. (C) 2008 Elsevier Ltd. All rights reserved.