Comparative Profiling of TG2 and Its Effectors in Human Relapsing Remitting and Progressive Multiple Sclerosis
Multiple Sclerosis (MS) is a chronic CNS autoimmune disease characterized by immune-mediated demyelination, axon loss, and disability. Dysregulation of transglutaminase-2 (TG2) has been implicated in disease initiation and progression. Herein, TG2 expression in post-mortem human brain tissue from Re...
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MDPI AG
2022-05-01
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| author | Damien D. Pearse Andrew B. Hefley Alejo A. Morales Mousumi Ghosh |
| author_facet | Damien D. Pearse Andrew B. Hefley Alejo A. Morales Mousumi Ghosh |
| author_sort | Damien D. Pearse |
| collection | DOAJ |
| description | Multiple Sclerosis (MS) is a chronic CNS autoimmune disease characterized by immune-mediated demyelination, axon loss, and disability. Dysregulation of transglutaminase-2 (TG2) has been implicated in disease initiation and progression. Herein, TG2 expression in post-mortem human brain tissue from Relapsing Remitting MS (RRMS) or Progressive MS (PMS) individuals were examined and correlated with the presence of TG2 binding partners and effectors implicated in the processes of inflammation, scar formation, and the antagonism of repair. Tissues from Relapsing-Remitting Multiple Sclerosis (RRMS; <i>n</i> = 6), Progressive Multiple Sclerosis (PMS; <i>n</i> = 5), and non-MS control (<i>n</i> = 6) patients underwent immunohistochemistry for TG2, PLA2, COX-2, FN, CSPG, and HSPG. TG2 was strongly upregulated in active RRMS and PMS lesions, within blood vessels and the perivascular tissue of sclerotic plaques. TG2 colocalization was observed with GFAP+ astrocytes and ECM, including FN, HSPG, and CSPG, which also increased in either RRMS or PMS lesions. Although TG2 was not colocalized with inflammatory mediators COX-2 and PLA2, or the macrophage-microglia marker Iba1, its increased expression correlated with their elevation in active RRMS and PMS lesions. In summary, the correlation of strong TG2 induction in either RRMS or PMS with some of its binding partners but not others implicates potentially different roles for TG2 in disparate MS forms that may warrant further investigation. |
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| language | English |
| last_indexed | 2024-03-10T00:21:25Z |
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| spelling | doaj.art-08e5e3b7c8c34aa29819d7cd7af226ca2023-11-23T15:41:23ZengMDPI AGBiomedicines2227-90592022-05-01106124110.3390/biomedicines10061241Comparative Profiling of TG2 and Its Effectors in Human Relapsing Remitting and Progressive Multiple SclerosisDamien D. Pearse0Andrew B. Hefley1Alejo A. Morales2Mousumi Ghosh3The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USAThe Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USAThe Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USAThe Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USAMultiple Sclerosis (MS) is a chronic CNS autoimmune disease characterized by immune-mediated demyelination, axon loss, and disability. Dysregulation of transglutaminase-2 (TG2) has been implicated in disease initiation and progression. Herein, TG2 expression in post-mortem human brain tissue from Relapsing Remitting MS (RRMS) or Progressive MS (PMS) individuals were examined and correlated with the presence of TG2 binding partners and effectors implicated in the processes of inflammation, scar formation, and the antagonism of repair. Tissues from Relapsing-Remitting Multiple Sclerosis (RRMS; <i>n</i> = 6), Progressive Multiple Sclerosis (PMS; <i>n</i> = 5), and non-MS control (<i>n</i> = 6) patients underwent immunohistochemistry for TG2, PLA2, COX-2, FN, CSPG, and HSPG. TG2 was strongly upregulated in active RRMS and PMS lesions, within blood vessels and the perivascular tissue of sclerotic plaques. TG2 colocalization was observed with GFAP+ astrocytes and ECM, including FN, HSPG, and CSPG, which also increased in either RRMS or PMS lesions. Although TG2 was not colocalized with inflammatory mediators COX-2 and PLA2, or the macrophage-microglia marker Iba1, its increased expression correlated with their elevation in active RRMS and PMS lesions. In summary, the correlation of strong TG2 induction in either RRMS or PMS with some of its binding partners but not others implicates potentially different roles for TG2 in disparate MS forms that may warrant further investigation.https://www.mdpi.com/2227-9059/10/6/1241Multiple SclerosisRelapsing-Remitting Multiple SclerosisProgressive Multiple Sclerosistransglutaminase-2blood–brain barrier disruptionperivascular lesion |
| spellingShingle | Damien D. Pearse Andrew B. Hefley Alejo A. Morales Mousumi Ghosh Comparative Profiling of TG2 and Its Effectors in Human Relapsing Remitting and Progressive Multiple Sclerosis Biomedicines Multiple Sclerosis Relapsing-Remitting Multiple Sclerosis Progressive Multiple Sclerosis transglutaminase-2 blood–brain barrier disruption perivascular lesion |
| title | Comparative Profiling of TG2 and Its Effectors in Human Relapsing Remitting and Progressive Multiple Sclerosis |
| title_full | Comparative Profiling of TG2 and Its Effectors in Human Relapsing Remitting and Progressive Multiple Sclerosis |
| title_fullStr | Comparative Profiling of TG2 and Its Effectors in Human Relapsing Remitting and Progressive Multiple Sclerosis |
| title_full_unstemmed | Comparative Profiling of TG2 and Its Effectors in Human Relapsing Remitting and Progressive Multiple Sclerosis |
| title_short | Comparative Profiling of TG2 and Its Effectors in Human Relapsing Remitting and Progressive Multiple Sclerosis |
| title_sort | comparative profiling of tg2 and its effectors in human relapsing remitting and progressive multiple sclerosis |
| topic | Multiple Sclerosis Relapsing-Remitting Multiple Sclerosis Progressive Multiple Sclerosis transglutaminase-2 blood–brain barrier disruption perivascular lesion |
| url | https://www.mdpi.com/2227-9059/10/6/1241 |
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