Axons modulate the expression of transforming growth factor-betas in Schwann cells.
We have investigated the expression of transforming growth factor (TGF)-beta 1,-beta 2, and -beta 3 in developing, degenerating, and regenerating rat peripheral nerve by immunohistochemistry and Northern blot analysis. In normal adult sciatic nerve, TGF-beta 1, -beta 2, and -beta 3 are detected in the cytoplasm of Schwann cells, and the levels of TGF-beta 1 and -beta 3 mRNAs are constant during post-natal development. When sciatic nerves are transected to cause axonal degeneration and prevent axonal regeneration, the level of TGF-beta 1 mRNA in the distal nerve-stump increases markedly and remains elevated, whereas the level of TGF-beta 3 mRNA falls modestly and remains depressed. When sciatic nerves are crushed to cause axonal degeneration and allow axonal regeneration, the level of TGF-beta 1 mRNA initially increases as axons degenerate, and then falls as axons regenerate. TGF-beta 2 mRNA was not detected in developing or lesioned sciatic nerves at any time. Cultured Schwann cells have high levels of TGF-beta 1 mRNA, the amount of which is reduced by forskolin, which mimics the effect of axonal contact. These data demonstrate that Schwann cells express TGF-beta 1, -beta 2, and -beta 3, and that TGF-beta 1 and -beta 3 mRNA predominate over TGF-beta 2 mRNA in peripheral nerve. Axonal contact and forskolin decrease the expression of TGF-beta 1 in Schwann cells.
Scherer
S S
SS
Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia 19104.
Kamholz
J
J
Jakowlew
S B
SB
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D015152:Blotting, Northern; D005576:Colforsin / Q000494:pharmacology; D007150:Immunohistochemistry; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D012583:Schwann Cells / Q000187:drug effects / Q000378:metabolism*; D012584:Sciatic Nerve / Q000254:growth & development / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D014855:Wallerian Degeneration / Q000502:physiology
D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D016212:Transforming Growth Factor beta; D005576:Colforsin