AXONS MODULATE THE EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETAS IN SCHWANN-CELLS

We have investigated the expression of transforming growth factor (TGF)-beta1, -beta2, and -beta3 in developing, degenerating, and regenerating rat peripheral nerve by immunohistochemistry and Northern blot analysis. In normal adult sciatic nerve, TGF-beta1,-beta2, and -beta3 are detected in the cytoplasm of Schwann cells, and the levels of TGF-beta1 and -beta3 mRNAs are constant during post-natal development. When sciatic nerves are transected to cause axonal degeneration and prevent axonal regeneration, the level of TGF-beta1 mRNA in the distal nerve-stump increases markedly and remains elevated, whereas the level of TGF-beta3 mRNA falls modestly and remains depressed. When sciatic nerves are crushed to cause axonal degeneration and allow axonal regeneration, the level of TGF-beta1 mRNA initially increases as axons degenerate, and then falls as axons regenerate. TGF-beta2 mRNA was not detected in developing or lesioned sciatic nerves at any time. Cultured Schwann cells have high levels of TGF-beta1 mRNA, the amount of which is reduced by forskolin, which mimicks the effect of axonal contact. These data demonstrate that Schwann cells express TGF-beta1, -beta2, and -beta3, and that TGF-beta1 and -beta3 mRNA predominate over TGF-beta2 mRNA in peripheral nerve. Axonal contact and forskolin decrease the expression of TGF-beta1 in Schwann cells. (C) 1993 Wiley-Liss, Inc.