SARS-CoV-2 spike protein-ACE2 interaction increases carbohydrate sulfotransferases and reduces N-acetylgalactosamine-4-sulfatase by p38 MAPK
作者机构：Jesse Brown VA Medical Center and University of Illinois at ChicagoChicagoIL 60612USA
出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)
年 卷 期：2024年第9卷第3期
页 面：1174-1185页
核心收录：
学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
基 金：Jesse Brown Veterans Affairs Medical Center Chicago IL USA
摘 要：Immunostaining in lungs of patients who died with CovID-19 infection showed increased intensity and distribution of chondroitin sulfate and decline in N-acetylgalactostamine-4-sulfatase(Arylsulfatase B;ARSB).To explain these findings,human small airway epithelial cells were exposed to the SARS-CoV-2 spike protein receptor binding domain(SPRBD)and transcriptional mechanisms were ***-p38 MAPK and phospho-SMAD3 increased following exposure to the SPRBD,and their inhibition suppressed the promoter activation of the carbohydrate sulfotransferases CHST15 and CHST11,which contributed to chondroitin sulfate *** in ARSB was mediated by phospho-38 MAPK-induced N-terminal Rb phosphorylation and an associated increase in Rb-E2F1 binding and decline in E2F1 binding to the ARSB *** increases in chondroitin sulfotransferases were inhibited when treated with phospho-p38-MAPK inhibitors,SMAD3(SIS3)inhibitors,as well as antihistamine desloratadine and antibiotic *** the mouse model of carrageenan-induced systemic inflammation,increases in phosphop38 MAPK and expression of CHST15 and CHST11 and declines in DNA-E2F binding and ARSB expression occurred in the lung,similar to theobserved effects in this SPRBD model of COVID-19 *** accumulation of chondroitin sulfates is associated with fibrotic lung conditions and diffuse alveolar damage,increased attention to p38-MAPK inhibition may be beneficial in amelioratingCovid-19infections.
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