Role of non-Smad signaling pathways in transforming growth factor beta (TGFβ)-induced expression of chondroitin sulfate proteoglycans (CSPGs) by reactive astrocytes

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dc.contributor.authorJahan, Naima
dc.contributor.examiningcommitteeHombach-klonisch, Sabine (Human Anatomy and Cell Science) Karimi, Soheila (Physiology)en_US
dc.contributor.supervisorHannila, Sari (Human Anatomy and Cell Science)en_US
dc.date.accessioned2013-12-11T20:19:29Z
dc.date.available2013-12-11T20:19:29Z
dc.date.issued2013-12-11
dc.degree.disciplineHuman Anatomy and Cell Scienceen_US
dc.degree.levelMaster of Science (M.Sc.)en_US
dc.description.abstractChondroitin 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.en_US
dc.description.noteFebruary 2014en_US
dc.identifier.urihttp://hdl.handle.net/1993/22301
dc.language.isoengen_US
dc.rightsopen accessen_US
dc.subjecttransforming growth factor betaen_US
dc.subjectTGFβen_US
dc.subjectchondroitin sulfate proteoglycansen_US
dc.subjectCSPGsen_US
dc.subjectastrogliosisen_US
dc.titleRole of non-Smad signaling pathways in transforming growth factor beta (TGFβ)-induced expression of chondroitin sulfate proteoglycans (CSPGs) by reactive astrocytesen_US
dc.typemaster thesisen_US
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