Table 3.
Characterization of protein markers of reactive astrogliosis divided by cellular localization.
| Protein Marker | Full Name | Information |
|---|---|---|
| Structural and Membrane Proteins | ||
| CD109 | cluster of differentiation receptor 109 | upregulated in pro-inflammatory astroglial activation, specific for astrocytes, low expression after LPS, high after MCAO |
| CD14 | cluster of differentiation receptor 14 | upregulated in pro-inflammatory astroglial activation |
| CD36 | cluster of differentiation receptor 36 | fatty acid transporter; upregulated in reactive astrocytes |
| CD44 | cluster of differentiation receptor 44 | surface receptor for hyaluronan; responsible for astroglia morphological changes; detected on long, unbranched human astrocytes |
| Cx30 | connexin 30 | transmembrane protein; strongly engaged in inflammatory activation of astrocytes |
| Cx43 | connexin 43 | transmembrane protein channel; engaged in inflammatory reactive astrogliosis |
| EMP1 | epithelial membrane protein | small membrane glycoprotein; regulates cellular proliferation |
| FABP7/BLBP | fatty acid-binding protein/brain lipid-binding protein | expressed in Bergmann and radial glia, and also by injured astrocytes |
| GFAP | glial fibrillary acidic protein | cytoskeleton-building protein; strong increase in expression observed in most pathological conditions including neurodegeneration and injuries; variability in its basal levels between structures |
| nestin | nestin | intermediate filament; expression increases after astrocyte activation by MCAO or stroke but not LPS |
| S1P3 | sphingosine-1 phosphate receptor 3 | cell-membrane protein; overexpressed by astrocytes in neuroinflammation, confirmed in rodents and humans; ability to modulate BBB permeability, activated by MCAO |
| STEAP4 | six transmembrane epithelial antigen of prostate 4 | membrane protein reducing Fe3+ and Cu++ ions; upregulated in inflammation, although not exclusive for astroglia |
| synemin | synemin | intermediate filament; expression increases after astrocyte activation |
| TGM1 | transglutaminase 1 | membrane-bound enzyme; creates mechanical barrier against infectious agents, specific for astrocytes, low expression after LPS, high after MCAO |
| vimentin | vimentin | intermediate filament; expression increases after astrocyte activation, both after MCAO and LPS |
| Secreted Proteins | ||
| C3 | complement component 3 | upregulated in course of neurodegenerative diseases, also expressed by microglia |
| CFB | complement factor B | element of alternate complement pathway activation modulating proliferation and degradation of blood cellular components during inflammation |
| CXCL10 | C-X-C motif chemokine 10 | pro-inflammatory protein; mediates an inflammatory response between neurons and glia |
| LCN2 | lipocalin 2 | secreted protein-binding iron ions; participates in innate immunity and apoptotic mechanisms, strong upregulation during reactive astrogliosis, expressed also by endothelial cells and microglia; colocalizes with GLAST |
| MFG-E8 | milk fat globulin protein E8 | secreted protein; responsible for removal of damaged neurons |
| MT | metallothionein | Metal-binding protein; found overexpressed in neurodegenerative diseases |
| MX1S | interferon-induced GTP-binding protein | acts against viral nucleic acids |
| PK2 | prokineticin-2 | chemokine-like protein; stimulates and promotes shift of astroglia phenotype into immunosuppressive when overexpressed by neurons and astrocytes |
| PTX3 | pentraxin 3 | directly related to the innate immunity response to pathogens; responsible for astroglial support of BBB integrity after ischemic stroke; activates classical complement pathway, specific for astrocytes, low expression after LPS, high after MCAO |
| Serpin A3N | serine protease inhibitor A3N | expression in resting state cells is below detection level; upregulated only in activated astrocytes; colocalizes with GLAST |
| Serpin G1 | plasma protease C1 inhibitor | interferes with C3 and CFB by physical binding influencing the alternate complement activation, increased in LPS activation |
| TIMP1 | tissue inhibitor of metalloproteinase 1 | forms complexes with MMPs irreversibly inactivating them; able to induce reactive astrogliosis; produced by astrocytes in response to pathophysiological threat |
| TN-C | tenascin | extracellular matrix protein; engaged in astroglia development and synaptic plasticity, marker of reactive astrocytes in stroke, neuronal injury or glial scar formation, induced by MCAO |
| TSP-1 | thrombospondin-1 | STAT-3-regulated factor; stimulates synaptogenesis, found upregulated after motor neuron injury along with GFAP |
| Intracellular Proteins | ||
| ALDOC | fructose-bisphosphate aldolase C | glycolytic enzyme; upregulated after spinal or brain injuries |
| ARG1 | arginase 1 | hydrolase; enzyme converting L-arginine in urea cycle, expressed in microglia but also in some astrocytes |
| FABP7 | fatty acid-binding protein | expressed by injured astrocytes and is specific to them |
| GBP2 | guanylate-binding protein 2 | transducer; reduces GTP by hydrolyzation, anti-viral properties |
| HSPB1/HSP27 | heat shock factor-binding protein 1 | chaperones; overexpressed in neurodegenerative diseases |
| HSPB5 | alpha-B crystallin | chaperones; overexpressed in neurodegenerative diseases |
| iNOS | inducible NO synthetase | cytoplasmic enzyme; engaged in cytokine-induced NO production during inflammatory response, strongly upregulated not only in microglia but also in reactive astrocytes |
| MAO-B | monoamine oxidase B | increase is a marker in neurodegenerative conditions affecting neurons releasing monoamines |
| NDRG2 | N-Myc downstream-regulated gene 2 | developmental protein; tumor suppressor and cellular stress-related protein associated with cell proliferation and differentiation; exclusively expressed by astrocytes |
| NFAT | nuclear factor of activated T cells | transcription factor |
| NRF2 | nuclear factor erythroid 2-related factor 2 | transcription factor; regulates gene expression related to oxidative stress and redox reactions; expressed exclusively in astrocytes in course of Parkinson’s disease, but additionally in microglia and neurons in Alzheimer’s disease |
| PTGS2 | prostaglandin G/H synthase 2 | responsible for stimulation of prostaglandin production; expression increased in injury and inflammation-related reactive astrogliosis |
| S100β | protein S100-B | cytosolic Ca++-binding protein; labels cell bodies of small astrocytes with less extended branching; preferentially marks gray matter cells complementing GFAP staining; actively secreted from astrocytes during cellular stress along with downregulation of its expression intracellularly |
| SOX9 | SRY-box transcription factor 9 | almost exclusively expressed by astrocytes in adult human CNS, strong upregulation reported in rodent ALS model |
| SPHK1 | sphingosine kinase-1 | catalyzes phosphorylation of sphingosine activating NFκB signaling and IL-17 secretion |
| STAT3 | signal transducer and activator of transcription 3 | JAK-STAT pathway element; necessary for astroglial differentiation; overexpressed by astroglia in injury-induced inflammation, but expressed by other cells |