Tissue-specific augmentation of circadian PAI-1 expression in mice with streptozotocin-induced diabetes.
Diabetes is associated with an excess risk of cardiac events, and the risk for infarction is partly determined by plasminogen activator inhibitor-1 (PAI-1). We found that plasma total and active PAI-1 levels increased in a circadian manner in mice with streptozotocin (STZ)-induced diabetes. Circadian expression of PAI-1 mRNA in the lung, heart, liver, and kidney increased in a tissue-specific manner. Peak to peak comparisons revealed that the mRNA expression levels increased by 1.7, 1.7, 1.2, and 1.6-fold in the heart, lung, liver, and kidney, respectively. In contrast, the circadian expression of the clock gene, mPer2, was preserved in the diabetic mice, suggesting that the altered expression of PAI-1 mRNA did not arise due to impaired circadian clocks. Our results suggest that impairment of the coagulation and fibrinolytic systems induced by diabetes is partly due to impaired circadian PAI-1 fluctuation at the level of mRNA expression.
Clock Cell Biology Research Group, Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology, Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.
Katsutaka
K
Oishi
Naoki
N
Ohkura
Manami
M
Kasamatsu
Nanae
N
Fukushima
Hidenori
H
Shirai
Juzo
J
Matsuda
Shuichi
S
Horie
Norio
N
Ishida
D000818:Animals; D015415:Biomarkers / Q000097:blood; D002940:Circadian Rhythm / Q000276:immunology*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008813:Mice, Inbred ICR; D009928:Organ Specificity; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000276:immunology* / Q000378:metabolism*; D014018:Tissue Distribution
D015415:Biomarkers; D017395:Plasminogen Activator Inhibitor 1