PRESENCE AND REGULATION OF TRANSFORMING GROWTH-FACTOR-BETA MESSENGER-RNA AND PROTEIN IN THE NORMAL AND LESIONED RAT SCIATIC-NERVE

The transforming growth factors beta (TGF-beta), a family of regulator y polypeptides, are involved in numerous vital processes including inf lammation and wound healing. Since repair of a peripheral nerve lesion includes a series of well-defined steps of cellular actions possibly controlled by TGF-beta s, and since TGF-beta mRNA and immunoreactivity have been found in the normal peripheral nerve, we have examined TGF- beta mRNA regulation and protein expression in the lesioned peripheral nerve. Sciatic nerves of adult rats were either crushed (allowing axo nal regeneration) or transected (to prevent axonal regeneration and to induce Wallerian degeneration in the distal stump). After intervals o f 6 hours, 2 and 6 days post-lesion, the rats were sacrificed and each nerve was cut into four segments, two proximal and two distal to the lesion site. TGF-beta 1-3 mRNA were determined for each segment. We de monstrate that TGF-beta 1 mRNA levels are higher than those of TGF-bet a 3; the amplitude of mRNA regulation depends on time, type of lesion and localization relative to the lesion site. TGF-beta 2 mRNA could no t be detected. For TGF-beta 1-3 immunocytochemistry, animals were sacr ificed 12, 24, 48, 72 hours and 7 and 14 days after surgery. TGF-beta immunoreactivity (IR) was observed for all isoforms in lesioned and un lesioned nerves. In the segment directly adjacent to the lesion at its proximal side, an increase of TGF-beta-IR became apparent as soon as 12 hours after surgery; it remained elevated during the whole period o bserved in both models. In the segment adjoining the distal side of th e lesion, an increase of TGF-beta-IR was observed after 48 hours, whic h was still present after 14 days. At day 7 after crush or transection , an increase of TGF-beta-IR was detected in the most distal segments, which reached its highest levels at the end of our observation period . Our results suggest that the presence of axonal contact might induce an enhancement of TGF-beta expression by Schwann cells in the distal stump of a lesioned and regenerating peripheral nerve. Since we demons trate an increase of TGF-beta mRNA and protein expression also in the distal stump of transected nerves where Schwann cells are not able to contact sprouting axons from the proximal part, other regulatory pathw ays must exist. The acquisition of a ''reactive'' Schwann cell phenoty pe after peripheral nerve lesion might involve an upregulation of TGF- beta expression. (C) 1994 Wiley-Liss, Inc.