Hyperglycemia-induced TGFbeta and fibronectin expression in embryonic mouse heart.
Cardiovascular defects are common in diabetic offspring, but their etiology and pathogenesis are poorly understood. Extracellular matrix accumulates in adult tissues in response to hyperglycemia, and transforming growth factor-beta1 (TGF beta1) likely mediates this effect. The objective of this study was to characterize TGF beta expression in the organogenesis-stage mouse heart and to evaluate TGF beta and fibronectin expression in embryonic mouse heart exposed to hyperglycemia. Prominent TGF beta1, and minimal TGF beta2 or TGF beta 3, protein expression was demonstrated in embryonic day (E) 9.5-E13.5 hearts. Hyperglycemia for 24 hr produced significantly increased fibronectin, slightly increased TGF beta1, and unchanged TGF beta2 or TGF beta 3, by immunohistochemistry. Increased TGF beta1 was demonstrated by enzyme-linked immunosorbent assay in embryonic fluid and isolated hearts after hyperglycemia for 24 hr, but not 48 hr. Hyperglycemia increased fibronectin protein and mRNA expression in embryonic hearts after 24 hr, and pericardial injection of TGF beta1 also increased fibronectin mRNA in the embryonic heart. It is proposed that TGF beta1 and fibronectin may play a role in diabetes-induced cardiac dysmorphogenesis.
Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, North Carolina.
Ida Washington
IW
Smoak
D000818:Animals; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006943:Hyperglycemia / Q000378:metabolism*; D051379:Mice; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3
D005353:Fibronectins; D012333:RNA, Messenger; C508961:Tgfb1 protein, mouse; C509045:Tgfb3 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3