Chondroitin sulphate proteoglycans (CSPGs) from the glial scar inhibit axonal regeneration following spinal cord injury. CSPG expression can be induced by transforming growth factor β (TGFβ), which suggests that inhibition of TGFβ may reduce CSPG levels. Astrocytes were treated with cyclic AMP (cAMP), which reduced TGFβ signaling protein Smad2 in astrocytes. However, cAMP-treated astrocytes showed strong neurocan expression following TGFβ treatment, which suggests that TGFβ may mediate CSPG expression through non-Smad pathways. Smad2 or Smad4 were knocked down in astrocytes using siRNA and TGFβ-induced neurocan, brevican and aggrecan expression were still observed, indicating that Smad signaling is not required for CSPG expression. Administration of a PI3K/Akt inhibitor produced significant reductions in neurocan, brevican and aggrecan expression in astrocytes, which suggests that PI3K/Akt pathway mediates CSPG expression. Erk1/2 inhibitor treatment did not reduce CSPG expression significantly. Targeting non-Smad signaling pathways may therefore be effective strategies to reduce CSPG expression following injury.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:MWU.1993/22301 |
| Date | 11 December 2013 |
| Creators | Jahan, Naima |
| Contributors | Hannila, Sari (Human Anatomy and Cell Science), Hombach-klonisch, Sabine (Human Anatomy and Cell Science) Karimi, Soheila (Physiology) |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Detected Language | English |
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