Changes that may occur in the localization of immunoreactive TGF- beta isoforms in pathological situations as compared to normal conditions are being investigated using specific peptide antibodies to TGF-beta proteins and the avidin-biotin peroxidase staining technique. For example, we have found that conditions which raise plasma renin activity, such as dehydration, cause an increase in TGF-beta immunostaining in the juxtaglomerular apparatus and certain arterioles in the mouse kidney. In childhood tumors, TGF- betas 1 and 3 are present in rhabdomyosarcomas and undifferentiated neuroblastomas, while TGF-beta2 is not observed. The roles of TGF- betas in vascular injury and in mediating cardioprotection are also being evaluated. Treatment of rats with endotoxin causes a striking decrease in immunoreactive TGF-beta in the vascular smooth muscle, while TGF-beta expression seems to increase following balloon injury of the aorta or carotid artery. Previous studies have shown that the localization of TGF-beta changes following myocardial infarction in rats and application of exogenous TGF-beta may limit tissue damage following ischemia. Isolated perfused hearts are being damaged by anoxia, cytokines and heat shock so that changes in cardiac function and expression of TGF-beta, matrix proteins and other cytokines can be examined. These studies will be extended to include the addition of exogenous TGF-beta during or following tissue damage to determine which parameters it modulates. Additionally, studies on effects of TGF-beta on expression of growth factors, proteases, gap junction proteins, cytokines and matrix proteins in primary cultures of neonatal rat cardiac fibroblasts and myocytes are beginning. In primary cultures of neonatal rat astrocytes, TGF-betas have ben found to antagonize the mitogenic effects of basic fibroblast growth factor, and to synergize with it to increase expression of collagen mRNA. TGF- beta is present in astrocytes in vivo and may play a role in reactive astrocytosis.
