Pearse Damien D, Hefley Andrew B, Morales Alejo A, Ghosh Mousumi
The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
The Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Biomedicines. 2022 May 26;10(6):1241. doi: 10.3390/biomedicines10061241.
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; = 6), Progressive Multiple Sclerosis (PMS; = 5), and non-MS control ( = 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.
多发性硬化症（MS）是一种慢性中枢神经系统自身免疫性疾病，其特征为免疫介导的脱髓鞘、轴突损失和残疾。转谷氨酰胺酶2（TG2）的失调与疾病的起始和进展有关。在此，研究了复发缓解型MS（RRMS）或进展型MS（PMS）个体的死后人类脑组织中TG2的表达，并将其与参与炎症、瘢痕形成和修复拮抗过程的TG2结合伴侣及效应物的存在情况进行关联分析。来自复发缓解型多发性硬化症（RRMS；n = 6）、进展型多发性硬化症（PMS；n = 5）和非MS对照（n = 6）患者的组织进行了TG2、磷脂酶A2（PLA2）、环氧化酶-2（COX-2）、纤连蛋白（FN）、硫酸软骨素蛋白聚糖（CSPG）和硫酸乙酰肝素蛋白聚糖（HSPG）的免疫组织化学检测。在RRMS和PMS的活动性病变中，以及硬化斑块的血管和血管周围组织中，TG2强烈上调。观察到TG2与GFAP +星形胶质细胞和细胞外基质（包括FN、HSPG和CSPG）共定位，这些物质在RRMS或PMS病变中也增加。尽管TG2未与炎症介质COX-2和PLA2或巨噬细胞-小胶质细胞标志物Iba1共定位，但其表达增加与RRMS和PMS活动性病变中它们的升高相关。总之，RRMS或PMS中强烈的TG2诱导与其一些结合伴侣而非其他伴侣的相关性表明，TG2在不同形式的MS中可能具有不同作用，这值得进一步研究。
