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甘露聚糖结合凝集素相关丝氨酸蛋白酶处于补体和凝血级联反应的交叉点——以新冠肺炎为例

MASPs at the crossroad between the complement and the coagulation cascades - the case for COVID-19.

作者信息

Bumiller-Bini Valéria, de Freitas Oliveira-Toré Camila, Carvalho Tamyres Mingorance, Kretzschmar Gabriela Canalli, Gonçalves Letícia Boslooper, Alencar Nina de Moura, Gasparetto Filho Miguel Angelo, Beltrame Marcia Holsbach, Winter Boldt Angelica Beate

机构信息

Universidade Federal do Paraná (UFPR), Departamento de Genética, Laboratório de Genética Molecular Humana, Curitiba, PR, Brazil.

Universidade Federal do Paraná (UFPR), Departamento de Genética, Programa de Pós-Graduação em Genética, Curitiba, PR, Brazil.

出版信息

Genet Mol Biol. 2021 Mar 17;44(1 Suppl 1):e20200199. doi: 10.1590/1678-4685-GMB-2020-0199. eCollection 2021.

Abstract

Components of the complement system and atypical parameters of coagulation were reported in COVID-19 patients, as well as the exacerbation of the inflammation and coagulation activity. Mannose binding lectin (MBL)- associated serine proteases (MASPs) play an important role in viral recognition and subsequent activation of the lectin pathway of the complement system and blood coagulation, connecting both processes. Genetic variants of MASP1 and MASP2 genes are further associated with different levels and functional efficiency of their encoded proteins, modulating susceptibility and severity to diseases. Our review highlights the possible role of MASPs in SARS-COV-2 binding and activation of the lectin pathway and blood coagulation cascades, as well as their associations with comorbidities of COVID-19. MASP-1 and/or MASP-2 present an increased expression in patients with COVID-19 risk factors: diabetes, arterial hypertension and cardiovascular disease, chronic kidney disease, chronic obstructive pulmonary disease, and cerebrovascular disease. Based also on the positive results of COVID-19 patients with anti-MASP-2 antibody, we propose the use of MASPs as a possible biomarker of the progression of COVID-19 and the investigation of new treatment strategies taking into consideration the dual role of MASPs, including MASP inhibitors as promising therapeutic targets against COVID-19.

摘要

在新冠病毒肺炎(COVID-19)患者中报告了补体系统的成分和非典型凝血参数,以及炎症和凝血活性的加剧。甘露糖结合凝集素(MBL)相关丝氨酸蛋白酶(MASP)在病毒识别以及随后补体系统凝集素途径和血液凝固的激活中起重要作用,将这两个过程联系起来。MASP1和MASP2基因的遗传变异进一步与其编码蛋白的不同水平和功能效率相关,调节对疾病的易感性和严重程度。我们的综述强调了MASP在严重急性呼吸综合征冠状病毒2(SARS-CoV-2)结合以及凝集素途径和凝血级联反应激活中的可能作用,以及它们与COVID-19合并症的关联。MASP-1和/或MASP-2在具有COVID-19风险因素的患者中表达增加,这些风险因素包括糖尿病、动脉高血压和心血管疾病、慢性肾病、慢性阻塞性肺疾病和脑血管疾病。同样基于COVID-19患者抗MASP-2抗体的阳性结果,我们建议将MASP用作COVID-19进展的可能生物标志物,并考虑到MASP的双重作用研究新的治疗策略,包括将MASP抑制剂作为对抗COVID-19的有前景的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28e0/7982787/e36ad28fae7a/1415-4757-GMB-44-1-s1-e20200199-gf1.jpg

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