Chondroitin 6‐sulphate synthesis is up‐regulated in injured CNS, induced by injury‐related cytokines and enhanced in axon‐growth inhibitory glia

Properzi, Francesca; Carulli, Daniela; Asher, Richard; Muir, Elizabeth M.; Camargo, Luiz Miguel; Kuppevelt, Toin H. Van; Dam, Gerdy B. ten; Furukawa, Yôko; Mikami, Tadishima; Sugahara, Kazuyuki; Toida, Toshihiko; Geller, Herbert M.; Fawcett, James W.

doi:10.1111/j.1460-9568.2005.03876.x

Cited by 174 publications

(176 citation statements)

References 71 publications

Supporting

Mentioning

166

Contrasting

Order By: Relevance

“…During neural development, CSPGs regulate axon growth and pathfinding (Snow et al, 1990;Jhaveri, 1993). After injury in the adult, they are enriched in scar tissues (McKeon et al, 1991;Levine, 1994;Lemons et al, 1999;Properzi et al, 2005), in which they contribute to hampering axon regeneration (Davies et al, 1997;Moon et al, 2001;Bradbury et al, 2002;Grimpe and Silver, 2002;Jones and Tuszynski, 2002) or compensatory sprouting (Tropea et al, 2003). In addition, several studies have highlighted their role in controlling structural plasticity in the absence of injury (Brakebusch et al, 2002;Pizzorusso et al, 2002;Miyata et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Degradation of Chondroitin Sulfate Proteoglycans Induces Sprouting of Intact Purkinje Axons in the Cerebellum of the Adult Rat

Corvetti¹,

Rossi²

2005

J. Neurosci.

124

View full text Add to dashboard Cite

Chondroitin sulfate proteoglycans are major constituents of the extracellular matrix and form perineuronal nets. Information regarding the growth-inhibitory activity of these molecules after injury is rapidly expanding. However, less is known about their physiological role in the adult undamaged CNS. Here, we investigated the function of chondroitin sulfate proteoglycans in maintaining the proper structure of Purkinje axons in the cerebellum of adult rats. To this end, we examined the morphology and distribution of intracortical Purkinje neurites after intraparenchymal injection of chondroitinase ABC. Staining with the lectin Wisteria floribunda agglutinin or 2B6 antibodies showed that this treatment efficiently removed chondroitin sulfate proteoglycans from wide areas of the cerebellar cortex. In the same sites, there was a profuse outgrowth of terminal branches from the Purkinje infraganglionic plexus, which invaded the deeper regions of the granular layer. In contrast, myelinated axon segments were not affected and maintained their normal relationship with oligodendroglial sheaths. Purkinje axon sprouting was first evident at 4 d and increased further at 7 d after enzyme application. Within 42 d, the expression pattern of chondroitin sulfate proteoglycans gradually recovered, whereas axonal modifications progressively regressed. Our results show that, in the absence of injury or novel external stimuli, degradation of chondroitin sulfate proteoglycans is sufficient to induce Purkinje axon sprouting but not the formation of long-lasting synaptic contacts. Together with other growth-inhibitory molecules, such as myelin-associated proteins, chondroitin sulfate proteoglycans restrict structural plasticity of intact Purkinje axons to maintain normal wiring patterns in the adult cerebellar cortex.

show abstract

Section: Introductionmentioning

confidence: 99%

Degradation of Chondroitin Sulfate Proteoglycans Induces Sprouting of Intact Purkinje Axons in the Cerebellum of the Adult Rat

Corvetti¹,

Rossi²

2005

J. Neurosci.

124

View full text Add to dashboard Cite

show abstract

“…CSPGs are composed of a protein core with associated chondroitin sulfate glycosaminoglycan (CS-GAG) side chains. In vitro, CS-GAG chains inhibit neurite outgrowth and repel axons (Asher et al, 2000;Properzi et al, 2005;Silver and Miller, 2004;Wang et al, 2008), as well as bind various growth factors and cytokines (Hirose et al, 2001). In vivo, removal of GAG chains with chondroitinase ABC following injury permits axonal sprouting (Bradbury et al, 2002), suggesting a primary functional role for GAG chains.…”

Section: Introductionmentioning

confidence: 99%

“…It has been proposed that the sulfation pattern on the GAGs confers specific biological activity on axonal growth, either inhibiting (Gilbert et al, 2005;Properzi et al, 2005;Wang et al, 2008) or promoting (Gama et al, 2006;Lin et al, 2011) growth. The majority of CS-GAG sulfation in the mammalian central nervous system is found as disaccharides with a sulfate group on the 4 or 6 position of GalNAc (Ishii and Maeda, 2008;Kitagawa et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Alterations in sulfated chondroitin glycosaminoglycans following controlled cortical impact injury in mice

Katagiri

Susarla

et al. 2012

J of Comparative Neurology

Self Cite

View full text Add to dashboard Cite

Chondroitin sulfate proteoglycans (CSPGs) play a pivotal role in many neuronal growth mechanisms including axon guidance and the modulation of repair processes following injury to the spinal cord or brain. Many actions of CSPGs in the central nervous system (CNS) are governed by the specific sulfation pattern on the glycosaminoglycan (GAG) chains attached to CSPG core proteins. To elucidate the role of CSPGs and sulfated GAG chains following traumatic brain injury (TBI), controlled cortical impact injury of mild to moderate severity was performed over the left sensory motor cortex in mice. Using immunoblotting and immunostaining, we found that TBI resulted in an increase in the CSPGs neurocan and NG2 expression in a tight band surrounding the injury core, which overlapped with the presence of 4-sulfated CS GAGs but not with 6-sulfated GAGs. This increase was observed as early as 7 days post injury (dpi), and persisted up to 28 dpi. Labeling with markers against microglia/macrophages, NG2 + cells, fibroblasts and astrocytes showed that these cells were all localized in the area, suggesting multiple origins of chondroitin-4-sultate increase. TBI also caused a decrease in the expression of aggrecan and phosphacan in the pericontusional cortex with a concomitant reduction in the number of perineuronal nets. In summary, we describe a dual response in CSPGs where they may be actively involved in complex repair processes following TBI. INDEXING TERMSChondroitin sulfate proteoglycan; traumatic brain injury; extracellular matrix; perineuronal nets

show abstract

“…[20][21][22][23] The balance of chondroitin sulfation is tightly controlled through spatial and temporal expression of distinct chondroitin sulfotransferase genes. 21,24,25 Moreover, this tightly controlled chondroitin sulfation balance has been shown to be disturbed in human disease and malignancies. [26][27][28][29][30][31] Carbohydrate sulfotransferase 11/Chondroitin-4-sulfotransferase-1 (CHST11/C4ST-1; subsequently named C4ST-1) catalyzes the transfer of sulfate to the C-4 position of CS disaccharides, thus creating chondroitin-4-sulfate (C4S) as one of its products.…”

Section: Introductionmentioning

confidence: 99%

C4ST-1/CHST11-controlled chondroitin sulfation interferes with oncogenic HRAS signaling in Costello syndrome

et al. 2012

View full text Add to dashboard Cite

Costello syndrome is a pediatric genetic disorder linked to oncogenic germline mutations in the HRAS gene. The disease is characterized by multiple developmental abnormalities, as well as predisposition to malignancies. Our recent observation that heart tissue from patients with Costello syndrome showed a loss of the glycosaminoglycan chondroitin-4-sulfate (C4S) inspired our present study aimed to explore a functional involvement of the chondroitin sulfate (CS) biosynthesis gene Carbohydrate sulfotransferase 11/Chondroitin-4-sulfotransferase-1 (CHST11/C4ST-1), as well as an impaired chondroitin sulfation balance, as a downstream mediator of oncogenic HRAS in Costello syndrome. Here we demonstrate a loss of C4S, as well as a reduction in C4ST-1 mRNA and protein expression, in primary fibroblasts from Costello syndrome patients. We go on to show that expression of oncogenic HRAS in normal fibroblasts can repress C4ST-1 expression, whereas interference with oncogenic HRAS signaling in Costello syndrome fibroblasts elevated C4ST-1 expression, thus identifying C4ST-1 as a negatively regulated target gene of HRAS signaling. Importantly, we show that forced expression of C4ST-1 in Costello fibroblasts could rescue the proliferation and elastogenesis defects associated with oncogenic HRAS signaling in these cells. Our results indicate reduced C4ST-1 expression and chondroitin sulfation imbalance mediating the effects of oncogenic HRAS signaling in the pathogenesis of Costello syndrome. Thus, our work identifies C4ST-1-dependent chondroitin sulfation as a downstream vulnerability in oncogenic RAS signaling, which might be pharmacologically exploited in future treatments of not only Costello syndrome and other RASopathies, but also human cancers associated with activating RAS mutations.

show abstract

Chondroitin 6‐sulphate synthesis is up‐regulated in injured CNS, induced by injury‐related cytokines and enhanced in axon‐growth inhibitory glia

Cited by 174 publications

References 71 publications

Degradation of Chondroitin Sulfate Proteoglycans Induces Sprouting of Intact Purkinje Axons in the Cerebellum of the Adult Rat

Degradation of Chondroitin Sulfate Proteoglycans Induces Sprouting of Intact Purkinje Axons in the Cerebellum of the Adult Rat

Alterations in sulfated chondroitin glycosaminoglycans following controlled cortical impact injury in mice

C4ST-1/CHST11-controlled chondroitin sulfation interferes with oncogenic HRAS signaling in Costello syndrome

Contact Info

Product

Resources

About