Axons modulate the expression of transforming growth factor‐betas in Schwann cells

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Abstract
We have investigated the expression of transforming growth factor (TGF)-β1,-β2, and -β3 in developing, degenerating, and regenerating rat peripheral nerve by immunohistochemistry and Northern blot analysis. In normal adult sciatic nerve, TGF-β1, -β2, and -β3 are detected in the cytoplasm of Schwann cells, and the levels of TGF-β1 and -β3 mRNAs are constant during post-natal development. When sciatic nerves are transected to cause axonal degeneration and prevent axonal regeneration, the level of TGF-β1 mRNA in the distal nerve-stump increases markedly and remains elevated, whereas the level of TGF-β3 mRNA falls modestly and remains depressed. When sciatic nerves are crushed to cause axonal degeneration and allow axonal regeneration, the level of TGF-β1 mRNA initially increases as axons degenerate, and then falls as axons regenerate. TGF-β2 mRNA was not detected in developing or lesioned sciatic nerves at any time. Cultured Schwann cells have high levels of TGF-β1 mRNA, the amount of which is reduced by forskolin, which mimicks the effect of axonal contact. These data demonstrate that Schwann cells express TGF-β1, -β2, and -β3, and that TGF-β1 and -β3 mRNA predominate over TGF-β2 mRNA in peripheral nerve. Axonal contact and forskolin decrease the expression of TGF-β1 in Schwann cells.