Rogister B, Delrée P, Leprince P, Martin D, Sadzot C, Malgrange B, Munaut C, Rigo J M, Lefebvre P P, Octave J N
Department of Human Physiology, University of Liège, Belgium.
J Neurosci Res. 1993 Jan;34(1):32-43. doi: 10.1002/jnr.490340105.
In contrast to the central nervous system (CNS), the peripheral nervous system (PNS) displays an important regenerative ability which is dependent, at least in part, on Schwann cell properties. The mechanisms which stimulate Schwann cells to adapt their behavior after a lesion to generate adequate conditions for PNS regeneration remain unknown. In this work, we report that adult rat dorsal root ganglion (DRG) neurons are able, after a lesion performed in vivo or when they are dissociated and cultured in vitro, to synthesize transforming growth factor beta (TGF beta), a pleiotropic growth factor implicated in wound healing processes and in carcinogenesis. This TGF beta is tentatively identified as the beta-1 isoform. Adult rat DRG neurons release a biologically active form of TGF beta which is able to elicit multiple Schwann cell responses including a stimulation to proliferate. Moreover, purified TGF beta-1 produces a Schwann cell morphology alteration and decreases the secretion of tissue-type plasminogen activator (tPA) and enhances the secretion of plasminogen activator inhibitor (PAI) by Schwann cells. This generates conditions which are thought to favor a successful neuritic regrowth. Furthermore, purified TGF beta-1 stimulates type IV collagen mRNA expression in Schwann cells. This subtype of collagen is associated with the process of myelinization. Finally, TGF beta-1 decreases nerve growth factor (NGF) mRNA expression by Schwann cells, an effect which could participate in the maintenance of a distoproximal NGF gradient during nerve regeneration. We propose that neuronal TGF beta plays an essential role as a neuronoglial signal that modulates the response of Schwann cells to injury and participates in the successful regeneration processes observed in the PNS.
与中枢神经系统（CNS）不同，外周神经系统（PNS）具有重要的再生能力，这至少部分依赖于雪旺细胞的特性。损伤后刺激雪旺细胞调整其行为以为PNS再生创造适宜条件的机制仍不清楚。在本研究中，我们报道成年大鼠背根神经节（DRG）神经元在体内损伤后或在体外分离培养时，能够合成转化生长因子β（TGFβ），这是一种多效性生长因子，与伤口愈合过程和致癌作用有关。这种TGFβ初步鉴定为β-1亚型。成年大鼠DRG神经元释放一种具有生物活性的TGFβ形式，它能够引发雪旺细胞的多种反应，包括刺激其增殖。此外，纯化的TGFβ-1可引起雪旺细胞形态改变，减少组织型纤溶酶原激活物（tPA）的分泌，并增强雪旺细胞纤溶酶原激活物抑制剂（PAI）的分泌。这创造了被认为有利于神经突起成功再生的条件。此外，纯化的TGFβ-1刺激雪旺细胞中IV型胶原mRNA的表达。这种胶原亚型与髓鞘形成过程有关。最后，TGFβ-1降低雪旺细胞神经生长因子（NGF）mRNA的表达，这一效应可能参与神经再生过程中远近端NGF梯度的维持。我们提出神经元TGFβ作为一种神经胶质信号发挥着重要作用，它调节雪旺细胞对损伤的反应，并参与PNS中观察到的成功再生过程。
