Immunomodulatory role of the extracellular matrix protein tenascin-C in neuroinflammation

Wiemann, Susanne; Reinhard, Jacqueline; Faissner, Andréas

doi:10.1042/bst20190081

Cited by 28 publications

(34 citation statements)

References 101 publications

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“…Our investigations of immunized WT and Tnc deficient mice lead to the assumption that Tnc promotes immunomodulatory processes of the neurotoxic M1-subtype in turns of higher activity. This is in line with previous reports that Tnc supports the activity of M1-microglia ( 36 , 111 ).…”

Section: Discussionsupporting

confidence: 93%

“…In regard to the temporal induction, Tnc expression levels were enhanced 3 days post injury and returned to normal levels 7 and 14 days after the induction of brain laser lesion ( 73 ). In the CNS, Tnc is re-expressed under pathological conditions and represents an important component of the glial scar ( 11 , 25 , 36 , 74 – 76 ). In Alzheimer's disease, Tnc immunoreactivity is highly associated with amyloid-β plaques ( 20 ).…”

Section: Discussionmentioning

confidence: 99%

“…Studies reported that Tnc is involved in the pathogenesis of CNS autoimmunity and astrocytes are a main Tnc source ( 24 , 29 , 30 , 34 – 36 ). Astrocytes are the major glial cells in the optic nerve head and provide neurotrophic as well as mechanical support for RGC axons.…”

Section: Discussionmentioning

confidence: 99%

“…Tnc is a key regulator of the immune system and plays an important role during neuroinflammation and glial response ( 34 – 36 ). Moreover, expression of Tnc by astrocytes is regulated by cytokines secreted by microglia ( 37 , 38 ).…”

Section: Introductionmentioning

confidence: 99%

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Loss of the Extracellular Matrix Molecule Tenascin-C Leads to Absence of Reactive Gliosis and Promotes Anti-inflammatory Cytokine Expression in an Autoimmune Glaucoma Mouse Model

et al. 2020

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Previous studies demonstrated that retinal damage correlates with a massive remodeling of extracellular matrix (ECM) molecules and reactive gliosis. However, the functional significance of the ECM in retinal neurodegeneration is still unknown. In the present study, we used an intraocular pressure (IOP) independent experimental autoimmune glaucoma (EAG) mouse model to examine the role of the ECM glycoprotein tenascin-C (Tnc). Wild type (WT ONA) and Tnc knockout (KO ONA) mice were immunized with an optic nerve antigen (ONA) homogenate and control groups (CO) obtained sodium chloride (WT CO, KO CO). IOP was measured weekly and electroretinographies were recorded at the end of the study. Ten weeks after immunization, we analyzed retinal ganglion cells (RGCs), glial cells, and the expression of different cytokines in retina and optic nerve tissue in all four groups. IOP and retinal function were comparable in all groups. Although RGC loss was less severe in KO ONA, WT as well as KO mice displayed a significant cell loss after immunization. Compared to KO ONA, less βIII-tubulin + axons, and downregulated oligodendrocyte markers were noted in WT ONA optic nerves. In retina and optic nerve, we found an enhanced GFAP + staining area of astrocytes in immunized WT. A significantly higher number of retinal Iba1 + microglia was found in WT ONA, while a lower number of Iba1 + cells was observed in KO ONA. Furthermore, an increased expression of the glial markers Gfap, Iba1, Nos2 , and Cd68 was detected in retinal and optic nerve tissue of WT ONA, whereas comparable levels were observed in KO ONA. In addition, pro-inflammatory Tnfa expression was upregulated in WT ONA, but downregulated in KO ONA. Vice versa, a significantly increased anti-inflammatory Tgfb1 expression was measured in KO ONA animals. We conclude that Tnc plays an important role in glial and inflammatory response during retinal neurodegeneration. Our results provide evidence that Tnc is involved in glaucomatous damage by regulating retinal glial activation and cytokine release. Thus, this transgenic EAG mouse model for the first time offers the possibility to investigate IOP-independent glaucomatous damage in direct relation to ECM remodeling.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Loss of the Extracellular Matrix Molecule Tenascin-C Leads to Absence of Reactive Gliosis and Promotes Anti-inflammatory Cytokine Expression in an Autoimmune Glaucoma Mouse Model

et al. 2020

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“…Fortunately, progress has been seen in studies on glioma, among which TNC has shown promise and may play a critical role in glioma pathology. TNC has been revealed to be associated with various aspects of neuron biology, such as the promotion and repression of synapses, neuroinflammation, and neural stem cell and glial progenitor cell proliferation and differentiation (Gottschling et al 2019;Wiemann et al 2019;Faissner et al 2017). In particular, a few findings indicate that TNC might be involved in glioma pathogenesis; however, these findings are far from conclusive.…”

Section: Discussionmentioning

confidence: 99%

Tenascin C Promotes Glioma Cell Malignant Behavior and Inhibits Chemosensitivity to Paclitaxel via Activation of the PI3K/AKT Signaling Pathway

Zhang

et al. 2021

J Mol Neurosci

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The present study aimed to detect the effect of tenascin C (TNC) on cell function and chemosensitivity to paclitaxel and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling in glioma cells.Human glioma cells U87, LN-229, T98G and U251 and normal human astrocytes were obtained, in which TNC expression was detected. The U87 cells and U251 cells were chosen and infected with lentivirus of control overexpression, TNC overexpression, control knockdown, and TNC knockdown for functional experiments. Rescue experiments were then performed to evaluate the effect of PI3K/AKT activator 740 Y-P on cell function and chemosensitivity to paclitaxel in TNC knockdown U251 cells. TNC mRNA and protein expression was elevated in glioma cells, including U87, LN-229, U251 and T98G cells, compared to normal human astrocytes. In U87 and U251 cells, TNC promoted proliferation while inhibiting apoptosis. In addition, TNC upregulated PI3K and p-AKT protein expression in U87 and U251 cells. As for chemosensitivity, TNC increased relative viability in U251 cells treated with 400 ng/mL and 800 ng/mL paclitaxel. In terms of stemness, TNC increased the sphere number per 1000 cells, CD44+CD133+ cell percentage and 1/stem cell frequency (assessed by extreme limiting dilution analysis) in U251 cells. In rescue experiments, 740 Y-P reduced the effect of TNC on proliferation, apoptosis, chemosensitivity to paclitaxel, and stemness in U251 cells. TNC acts as an oncogenic factor by promoting cancer cell proliferation and stemness while inhibiting apoptosis and chemosensitivity to paclitaxel in glioma via modulation of PI3K/AKT signaling.

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Tenascin-C preserves microglia surveillance and restricts leukocyte and, more specifically, T cell infiltration of the ischemic brain

Manrique-Castano

Dzyubenko

Borbor

et al. 2021

Brain, Behavior, and Immunity

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Immunomodulatory role of the extracellular matrix protein tenascin-C in neuroinflammation

Cited by 28 publications

References 101 publications

Loss of the Extracellular Matrix Molecule Tenascin-C Leads to Absence of Reactive Gliosis and Promotes Anti-inflammatory Cytokine Expression in an Autoimmune Glaucoma Mouse Model

Loss of the Extracellular Matrix Molecule Tenascin-C Leads to Absence of Reactive Gliosis and Promotes Anti-inflammatory Cytokine Expression in an Autoimmune Glaucoma Mouse Model

Tenascin C Promotes Glioma Cell Malignant Behavior and Inhibits Chemosensitivity to Paclitaxel via Activation of the PI3K/AKT Signaling Pathway

Tenascin-C preserves microglia surveillance and restricts leukocyte and, more specifically, T cell infiltration of the ischemic brain

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