Transforming growth factor β-induced expression of chondroitin sulfate proteoglycans is mediated through non-Smad signaling pathways

Jahan, Naima; Hannila, Sari S.

doi:10.1016/j.expneurol.2014.10.023

Cited by 39 publications

(32 citation statements)

References 56 publications

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“…Many studies have demonstrated that TGF‐β1 is a potent inducer of glial scars and their associated neurite outgrowth inhibitor molecules, including CSPG formation . Similar to previous studies, our current data also show a rapid and dramatic increase in TGF‐β1 expression after SCI .…”

Section: Discussionsupporting

confidence: 89%

Neuroprotective Effects of Direct Intrathecal Administration of Granulocyte Colony‐Stimulating Factor in Rats with Spinal Cord Injury

Chen

et al. 2015

CNS Neurosci Ther

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Section: Discussionsupporting

confidence: 89%

Neuroprotective Effects of Direct Intrathecal Administration of Granulocyte Colony‐Stimulating Factor in Rats with Spinal Cord Injury

Chen

et al. 2015

CNS Neurosci Ther

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“…Transforming growth factor β receptor 2 (TGFBR2), which showed a 7–9-fold increase in gene expression from 1 M to 6 M post-SCI, had the most connections in the network, suggesting its important roles in gliosis. This is consistent with previous studies which suggest its ligand, TGF-β, functions as an essential regulatory factor of astrocyte function34 and gliosis by inducing synthesis of chondroitin sulfate proteoglycans35.…”

Section: Discussionsupporting

confidence: 93%

The systematic analysis of coding and long non-coding RNAs in the sub-chronic and chronic stages of spinal cord injury

Duran

Yan

Zheng

et al. 2017

Sci Rep

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Spinal cord injury (SCI) remains one of the most debilitating neurological disorders and the majority of SCI patients are in the chronic phase. Previous studies of SCI have usually focused on few genes and pathways at a time. In particular, the biological roles of long non-coding RNAs (lncRNAs) have never been characterized in SCI. Our study is the first to comprehensively investigate alterations in the expression of both coding and long non-coding genes in the sub-chronic and chronic stages of SCI using RNA-Sequencing. Through pathway analysis and network construction, the functions of differentially expressed genes were analyzed systematically. Furthermore, we predicted the potential regulatory function of non-coding transcripts, revealed enriched motifs of transcription factors in the upstream regulatory regions of differentially expressed lncRNAs, and identified differentially expressed lncRNAs homologous to human genomic regions which contain single-nucleotide polymorphisms associated with diseases. Overall, these results revealed critical pathways and networks that exhibit sustained alterations at the sub-chronic and chronic stages of SCI, highlighting the temporal regulation of pathological processes including astrogliosis. This study also provided an unprecedented resource and a new catalogue of lncRNAs potentially involved in the regulation and progression of SCI.

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“…Here, increased proliferation and migration of cultured spinal astrocytes in response to growth factor stimulation in vitro could be prevented with rapamycin, and systemic rapamycin treatment was able to reduce astrocyte reactivity and migration of GFAP‐positive astrocytes into the injury epicentre following ischemic SCI in vivo. Jahan and Hannila () demonstrated that TGFβ treatment of rat cortical astrocytes resulted in hypertrophy and the production of the CSPGs neurocan, brevican, and aggrecan in vitro, and that CSPG production in response to TGFβ was inhibited by rapamycin. Thus, rapamycin treatment may also be effective in preventing CSPG production by hypertrophic, reactive astrocytes through inhibition of TGFβ and mTor signalling.…”

Section: Discussionmentioning

confidence: 99%

Combinatorial tissue engineering partially restores function after spinal cord injury

Hakim

Rodysill

Chen

et al. 2019

J Tissue Eng Regen Med

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Hydrogel scaffolds provide a beneficial microenvironment in transected rat spinal cord. A combinatorial biomaterials‐based strategy provided a microenvironment that facilitated regeneration while reducing foreign body reaction to the three‐dimensional spinal cord construct. We used poly lactic‐co‐glycolic acid microspheres to provide sustained release of rapamycin from Schwann cell (SC)‐loaded, positively charged oligo‐polyethylene glycol fumarate scaffolds. The biological activity and dose‐release characteristics of rapamycin from microspheres alone and from microspheres embedded in the scaffold were determined in vitro. Three dose formulations of rapamycin were compared with controls in 53 rats. We observed a dose‐dependent reduction in the fibrotic reaction to the scaffold and improved functional recovery over 6 weeks. Recovery was replicated in a second cohort of 28 animals that included retransection injury. Immunohistochemical and stereological analysis demonstrated that blood vessel number, surface area, vessel diameter, basement membrane collagen, and microvessel phenotype within the regenerated tissue was dependent on the presence of SCs and rapamycin. TRITC‐dextran injection demonstrated enhanced perfusion into scaffold channels. Rapamycin also increased the number of descending regenerated axons, as assessed by Fast Blue retrograde axonal tracing. These results demonstrate that normalization of the neovasculature was associated with enhanced axonal regeneration and improved function after spinal cord transection.

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Transforming growth factor β-induced expression of chondroitin sulfate proteoglycans is mediated through non-Smad signaling pathways

Cited by 39 publications

References 56 publications

Neuroprotective Effects of Direct Intrathecal Administration of Granulocyte Colony‐Stimulating Factor in Rats with Spinal Cord Injury

Neuroprotective Effects of Direct Intrathecal Administration of Granulocyte Colony‐Stimulating Factor in Rats with Spinal Cord Injury

The systematic analysis of coding and long non-coding RNAs in the sub-chronic and chronic stages of spinal cord injury

Combinatorial tissue engineering partially restores function after spinal cord injury

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