In vivo proliferation, migration and phenotypic changes of Schwann cells in the presence of myelinated fibers

Cheng, Chun; Zochodne, Douglas W.

doi:10.1016/s0306-4522(02)00291-9

Cited by 95 publications

(79 citation statements)

References 36 publications

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“…In the present study, we further found GFAP-positive Schwann cells upregulated in C6st1 expression in the crushed nerve. GFAP expression is characteristic of both immature and non-myelinating Schwann cells (Jessen et al, 1990;Jessen and Mirsky, 2005) and is recapitulated as early as 24 hours after nerve injury (Cheng and Zochodne, 2002). Given an association of GFAP expression with Schwann cell motility, we suggest that enzymatic activity of the upregulated C6st1 yields 6-sulphated chondroitin products that modulate adhesion of Schwann cells to the basal lamina in coordination with the increased cell motility.…”

Section: Discussionmentioning

confidence: 65%

Upregulation of chondroitin 6-sulphotransferase-1 facilitates Schwann cell migration during axonal growth

Chau

Liu

et al. 2006

Journal of Cell Science

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Cell migration is central to development and post-traumatic regeneration. The differential increase in 6-sulphated chondroitins during axonal growth in both crushed sciatic nerves and brain development suggests that chondroitin 6-sulphotransferase-1 (C6ST-1) is a key enzyme that mediates cell migration in the process. We have cloned the cDNA of the C6ST-1 gene (C6st1) (GenBank accession number AF178689) from crushed sciatic nerves of adult rats and produced ribonucleotide probes accordingly to track signs of 6-sulphated chondroitins at the site of injury. We found C6st1 mRNA expression in Schwann cells emigrating from explants of both sciatic nerve segments and embryonic dorsal root ganglia. Immunocytochemistry indicated pericellular 6-sulphated chondroitin products around C6ST-1-expressing frontier cells. Motility analysis of frontier cells in cultures subjected to staged treatment with chondroitinase ABC indicated that freshly produced 6-sulphated chondroitin moieties facilitated Schwann cell motility, unlike restrictions resulting from proteoglycan interaction with matrix components. Sciatic nerve crush provided further evidence of in vivo upregulation of the C6ST-1 gene in mobile Schwann cells that guided axonal regrowth 1-14 days post crush; downregulation then accompanied declining mobility of Schwann cells as they engaged in the myelination of re-growing axons. These findings are the first to identify upregulated C6st1 gene expression correlating with the motility of Schwann cells that guide growing axons through both developmental and injured environments.

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Section: Discussionmentioning

confidence: 65%

Upregulation of chondroitin 6-sulphotransferase-1 facilitates Schwann cell migration during axonal growth

Chau

Liu

et al. 2006

Journal of Cell Science

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“…In situ hybridization confirmed that the upregulation of miR-221/222 primarily occurred in SCs at 4 days after injury in the proximal stumps of nerve. miR-221/222 upregulation is in agreement with the process of nerve regeneration in that proliferative activity reaches a peak in 4-11 days in the proximal stump of transected sciatic nerves (Cheng and Zochodne, 2002). Primary culture of SCs is thought to be the most accurate model for the physiology of SCs in severely injured and/or denervated peripheral nerves (Woodhoo et al, 2009).…”

Section: Discussionmentioning

confidence: 68%

miR-221/222 promote Schwann cell proliferation and migration by targeting LASS2 following sciatic nerve injury

Zhou

Wang

et al. 2012

Journal of Cell Science

105

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Summary microRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level. Their roles in regulating the responses of Schwann cells (SCs) to injury stimuli remain unexplored. Here we report dynamic alteration of miRNA expression following rat sciatic nerve injury using microarray analysis. We harvested the proximal nerve stumps and identified 77 miRNAs that showed significant changes at four time points after nerve transection. Subsequently, we analyzed the expression pattern of miRNA, selected one significant profile, and then integrated putative miRNA targets with differentially expressed mRNA yielding 274 potential targets. The 274 targets were mainly involved in cell proliferation, cell locomotion and cellular homeostasis that were known to play important roles in modulating cell phenotype. The upregulation of the miR-221 and miR-222 cluster (miR-221/222) was found to correlate with the injury-induced SC phenotypic modulation. Enhanced expression of miR-221/222 could promote SC proliferation and migration in vitro, whereas silencing their expression resulted in a reduced proliferation and migration. Further studies revealed that longevity assurance homologue 2 (LASS2) was a direct target of miR-221/222 in SCs because miR-221/222 bound directly to the 39-untranslated region of LASS2, thus reducing both mRNA and protein levels of LASS2. Silencing of LASS2 recapitulated the effects of miR-221/222 mimics, whereas enforced knockdown of LASS2 reversed the suppressive effects of miR-221/222 inhibitors. Our findings indicate that injury promotes SC proliferation and migration through the regulation of miR-221/222 by targeting LASS2, and provide new insights into the role of miRNAs in nerve regeneration.

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“…WT and TTR KO mice underwent bilateral nerve crush and were allowed to recover for 5 d. To label dividing cells, 100 g/g body weight of BrdU (5-bromo-2Ј-deoxyuridine, Sigma) was injected intraperitoneally 4 and 2 h before kill. Labeling of proliferating cells was performed 5 d after injury, since at this time point, Schwann cells reach their maximum proliferative activity in injured sciatic nerves (Cheng and Zochodne, 2002). Mice were killed using a lethal anesthesia dosage and the sciatic nerves were collected and processed for immunohistochemistry.…”

Section: Methodsmentioning

confidence: 99%

Transthyretin Internalization by Sensory Neurons Is Megalin Mediated and Necessary for Its Neuritogenic Activity

Fleming¹,

Mar²,

Franquinho³

et al. 2009

J. Neurosci.

103

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Mutated transthyretin (TTR) causes familial amyloid polyneuropathy, a neurodegenerative disorder characterized by TTR deposition in the peripheral nervous system (PNS). The origin/reason for TTR deposition in the nerve is unknown. Here we demonstrate that both endogenous mouse TTR and TTR injected intravenously have access to the mouse sciatic nerve. We previously determined that in the absence of TTR, both neurite outgrowth in vitro and nerve regeneration in vivo were impaired. Reinforcing this finding, we now show that local TTR delivery to the crushed sciatic nerve rescues the regeneration phenotype of TTR knock-out (KO) mice. As the absence of TTR was unrelated to neuronal survival, we further evaluated the Schwann cell and inflammatory response to injury, as well as axonal retrograde transport, in the presence/absence of TTR. Only retrograde transport was impaired in TTR KO mice which, in addition to the neurite outgrowth impairment, might account for the decreased regeneration in this strain. Moreover, we show that in vitro, in dorsal root ganglia neurons, clathrin-dependent megalin-mediated TTR internalization is needed for TTR neuritogenic activity. Supporting this observation, we demonstrate that in vivo, decreased levels of megalin lead to decreased nerve regeneration and that megalin's action as a regeneration enhancer is dependent on TTR. In conclusion, our work unravels the mechanism of TTR action during nerve regeneration. Additionally, TTR presence in the nerve, as is here shown, may underlie its preferential deposition in the PNS of familial amyloid polyneuropathy patients.

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In vivo proliferation, migration and phenotypic changes of Schwann cells in the presence of myelinated fibers

Cited by 95 publications

References 36 publications

Upregulation of chondroitin 6-sulphotransferase-1 facilitates Schwann cell migration during axonal growth

Upregulation of chondroitin 6-sulphotransferase-1 facilitates Schwann cell migration during axonal growth

miR-221/222 promote Schwann cell proliferation and migration by targeting LASS2 following sciatic nerve injury

Transthyretin Internalization by Sensory Neurons Is Megalin Mediated and Necessary for Its Neuritogenic Activity

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