Functional importance of the TGF-β1/Smad3 signaling pathway in oxygen-glucose-deprived (OGD) microglia and rats with cerebral ischemia.

We investigated the transforming growth factor-b1 (TGF-β1)/Smad3 signaling pathway in rats with cerebral ischemia and oxygen-glucose-deprived (OGD) microglia. Cerebral ischemia is a clinical condition that occurs when insufficient blood flows to the brain to maintain metabolic activity. TGF-β1 is a well-known functional peptide that regulates cell differentiation, migration, proliferation, and apoptosis. In the current study, we determined the infarct size and TGF-β1/Smad3 protein expression in stroke-induced rats. Apoptosis and TGF-β1/Smad3 mRNA and protein expression were determined in transfected OGD human microglial cells. TGF-β1 treatment resulted in smaller infarct regions than in control cells, whereas TGF-β1 inhibitor treatment resulted in larger infarcts. The TGF-β1-treated groups showed substantial TGF-β1 and Smad3 expression by immunofluorescence compared to the controls. Apoptosis was significantly reduced in TGF-β1- and Smad3-transfected cells, and an increased rate of apoptosis was observed in Smad3 or TGF-β1 siRNA-transfected cells. TGF-β1 and Smad3 mRNA and protein expression increased following TGF-β1 and Smad3 transfection. Taken together, our experimental results show that Smad3 and TGF-β1 play a protective role against ischemic stroke, as demonstrated by the reduced infarct size. Smad3 and TGF-β1 expression was increased in cells transfected with TGF-β1, whereas Smad3 and TGF-β1 expression was increased in TGF-β1 inhibitor-transfected cells.