Hyperthermia induces expression of transforming growth factor-beta s in rat cardiac cells in vitro and in vivo.
Hyperthermia causes changes in expression of TGF-beta mRNA and protein in cultured cardiac cells, as well as in the heart in vivo. 12 h after hyperthermia, primary cultures of neonatal rat cardiomyocytes show a two- to threefold decreased expression of TGF-beta mRNAs which returns to control levels by 48 h after heat shock. In cultures of cardiac fibroblasts, expression of TGF-beta mRNAs increases 5-25-fold, 12-48 h after heat shock, while fetal bovine heart endothelial cells show little change in TGF-beta expression after hyperthermia. In each case, mRNAs for TGF-beta s 1, 2, and 3 are regulated similarly. Hearts isolated from rats exposed to hyperthermia show an initial 20-fold decrease in TGF-beta 1 and 3 mRNA levels which return to control levels by 24 h and subsequently are elevated two- to threefold above normal 48-72 h after heat shock; there is little change in TGF-beta 2 mRNA. Expression of immunoreactive TGF-beta 1 and 3 protein, localized intracellularly in myocytes, follows the same pattern as the mRNA expression. By 72 h, some myocytes show hyperstaining for TGF-beta 1. Staining for extracellular TGF-beta 1/3 exhibits the opposite time course, being most intense 3-6 h after heat shock and returning to control levels by 48 h. The increase in TGF-beta s after hyperthermia could play a role in mediating the reported cardioprotective effects of heat shock.
Flanders
K C
KC
Laboratory of Chemoprevention, National Cancer Institute, Bethesda, Maryland 20892.
Winokur
T S
TS
Holder
M G
MG
Sporn
M B
MB
D002478:Cells, Cultured; D015870:Gene Expression; D006360:Heat-Shock Proteins / Q000235:genetics; D006358:Hot Temperature; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta