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- Title
The Low-Density Lipoprotein Receptor-Related Protein Is a Pro-Survival Receptor in Schwann Cells: Possible Implications in Peripheral Nerve Injury.
- Authors
Campana, W. Marie; Xiaoqing Li; Dragojlovic, Nikola; Janes, Julie; Gaultier, Alban; Gonias, Steven L.
- Abstract
Schwann cells undergo phenotypic modulation in peripheral nerve injury. In the adult rodent, Schwann cells are resistant to death-promoting challenges. The responsible receptors and signaling pathways are incompletely understood. In this study, we demonstrate that low-density lipoprotein receptor-related protein-1 (LRP-1) is expressed in adult sciatic nerve. After crush injury, LRP-1 is lost from the axoplasm and substantially upregulated in Schwann cells. Increased LRP-1 mRNA expression was observed locally at the injury site in multiple forms of sciatic nerve injury, including crush injury, chronic constriction injury, and axotomy. Endogenously produced tumor necrosis factor-α(TNF-α) was mostly responsible for the increase in LRP-1 expression; this activity was reproduced by direct injection of TNF-αinto injured nerves in the TNF-αgene knock-out mouse.TNFreceptor II was primarily involved. TNF-αalso increased LRP-1 mRNA in Schwann cells in primary culture. Silencing of Schwann cell LRP-1 with siRNA decreased phosphorylated Akt and increased activated caspase-3. Equivalent changes in cell signaling were observed in LRP-1-deficient murine embryonic fibroblasts. Schwann cell death was induced in vitro by serum withdrawal or TNF-α, to a greater extent when LRP-1 was silenced. Schwann cell death was induced in vivo by injecting the LRP-1 antagonist, receptor-associated protein, into axotomy sites in adult rats. These results support a model in which LRP-1 functions as a pro-survival receptor in Schwann cells.
- Subjects
CELLS; NERVOUS system injuries; LABORATORY rodents; LIPOPROTEINS; SCIATIC nerve
- Publication
Journal of Neuroscience, 2006, Vol 26, Issue 43, p11197
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.2709-06.2006