Leukaemia inhibitory factor alters expression of genes involved in rat cardiomyocyte energy metabolism.
OBJECTIVE
Cardiac remodelling is associated with changes in contractile proteins and their performance, alterations in energy production and intracellular calcium homeostasis, as well as changes in extracellular matrix proteins. Some of these processes may be mediated through the gp130 receptor complex. Patients with heart failure have increased cardiac gene expression of leukaemia inhibitory factor (LIF), a cytokine that signals through the gp130 receptor. The aim of this study was to identify alterations in gene expression in LIF-stimulated neonatal cardiomyocytes.


METHODS
Cardiomyocytes were isolated from 1- to 3-day-old Wistar rats and stimulated for 48 h with LIF. Gene expression was examined by repeated cDNA filter array analysis (n = 5) and key results verified by complementary methods.


RESULTS
In LIF-stimulated cultures we observed increased cell area and changes in gene expression. The intracellular signal regulators signal transducer and activator of transcription 3, calcium/calmodulin-dependent protein kinase IV, protein kinase Cdelta and the transcription factor ID1 were upregulated. Adenylyl cyclase V was downregulated. LIF also induced altered expression of tissue inhibitor of metalloproteinase-1. Receptor genes for tumour necrosis factor, interleukin-4, neurotensin and somatostatin were upregulated. Finally, LIF reduced the expression of components in the adenosine triphosphate synthase complex, epidermal fatty acid-binding protein and insulin-like growth factor-binding proteins 1 and 6.


CONCLUSIONS
Array analysis revealed changes in mRNA levels of several genes not previously associated with activation of the gp130/LIF receptor complex. Our findings indicate a role for LIF in regulation of cardiomyocyte energy metabolism.
Florholmen
G
G
Institute for Experimental Medical Research, Ullevål University Hospital, University of Oslo, Oslo, Norway.
Andersson
K B
KB
Yndestad
A
A
Austbø
B
B
Henriksen
U L
UL
Christensen
G
G
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000032:analysis; D015152:Blotting, Northern / Q000379:methods; D002478:Cells, Cultured; D015536:Down-Regulation; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D053605:Leukemia Inhibitory Factor; D008565:Membrane Proteins / Q000032:analysis; D008855:Microscopy, Electron, Scanning; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009206:Myocardium / Q000166:cytology* / Q000648:ultrastructure; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis; D015854:Up-Regulation
D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008565:Membrane Proteins; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D009320:Atrial Natriuretic Factor