HOX genes in human lung: altered expression in primary pulmonary hypertension and emphysema.
HOX genes belong to the large family of homeodomain genes that function as transcription factors. Animal studies indicate that they play an essential role in lung development. We investigated the expression pattern of HOX genes in human lung tissue by using microarray and degenerate reverse transcriptase-polymerase chain reaction survey techniques. HOX genes predominantly from the 3' end of clusters A and B were expressed in normal human adult lung and among them HOXA5 was the most abundant, followed by HOXB2 and HOXB6. In fetal (12 weeks old) and diseased lung specimens (emphysema, primary pulmonary hypertension) additional HOX genes from clusters C and D were expressed. Using in situ hybridization, transcripts for HOXA5 were predominantly found in alveolar septal and epithelial cells, both in normal and diseased lungs. A 2.5-fold increase in HOXA5 mRNA expression was demonstrated by quantitative reverse transcriptase-polymerase chain reaction in primary pulmonary hypertension lung specimens when compared to normal lung tissue. In conclusion, we demonstrate that HOX genes are selectively expressed in the human lung. Differences in the pattern of HOX gene expression exist among fetal, adult, and diseased lung specimens. The altered pattern of HOX gene expression may contribute to the development of pulmonary diseases.
Pulmonary Hypertension Center, University of Colorado Health Sciences Center, 4200 E. Ninth Ave., Denver, CO 80262, USA.
H A
HA
Golpon
M W
MW
Geraci
M D
MD
Moore
H L
HL
Miller
G J
GJ
Miller
R M
RM
Tuder
N F
NF
Voelkel
D000328:Adult; D000818:Animals; D020869:Gene Expression Profiling; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics* / Q000378:metabolism; D008168:Lung / Q000196:embryology / Q000378:metabolism*; D051379:Mice; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D011656:Pulmonary Emphysema / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D015533:Transcriptional Activation
C489213:HOXA5 protein, human; C086061:HOXB2 protein, human; C093252:HOXB6 protein, human; D018398:Homeodomain Proteins; C059637:Hoxa5 protein, mouse; C490111:Hoxb2 protein, mouse; C490537:Hoxb6 protein, mouse; D010750:Phosphoproteins; D020033:Protein Isoforms; D014157:Transcription Factors