Temporal correlation between transcriptional changes and increased synthesis of hyaluronan in experimental cardiac hypertrophy.
The role of hyaluronan in cardiac growth has become evident, previously shown by increased myocardial levels of hyaluronan in a rat model of cardiac hypertrophy. To further investigate the role of hyaluronan and regulation of its synthesis in cardiac hypertrophy, quantitative measurements of myocardial hyaluronan concentration was correlated to gene transcription in hypertrophic cardiac tissue. Factor analysis was used to study this correlation over time. A subset of differentially expressed genes was identified with a transcriptional regulation correlating to the increased synthesis of hyaluronan, suggesting a common regulatory pathway. Four transcription factors, Myc, Fos, Junb and Egr1, were also up-regulated. Furthermore, the Ace gene was up-regulated, representing increase of angiotensin II, an inducer of these transcription factors and fetal genes in cardiac hypertrophy. This demonstrates a coordinated synthesis of hyaluronan and pro-hypertrophic gene expression, regulated by immediate early genes, with angiotensin II as a possible mediator.
Hellman
Urban
U
Department of Public Health and Clinical Medicine/Medicine, Umeå University, Sweden. urban.hellman@medbio.umu.se
Mörner
Stellan
S
Engström-Laurent
Anna
A
Samuel
Jane-Lise
JL
Waldenström
Anders
A
D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism*; D005163:Factor Analysis, Statistical; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D017781:Genes, Immediate-Early / Q000235:genetics / Q000502:physiology; D006820:Hyaluronic Acid / Q000096:biosynthesis*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013053:Spectrophotometry; D018709:Statistics, Nonparametric; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
D014157:Transcription Factors; D006820:Hyaluronic Acid; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2