Department of Internal Clinic, Botucatu Medicine School, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil.
Department of Internal Clinic, Botucatu Medicine School, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil.
Mol Cell Endocrinol. 2020 Sep 15;515:110917. doi: 10.1016/j.mce.2020.110917. Epub 2020 Jun 25.
Obesity patients are more susceptible to develop COVID-19 severe outcome due to the role of angiotensin-converting enzyme 2 (ACE2) in the viral infection. ACE2 is regulated in the human cells by different genes associated with increased (TLR3, HAT1, HDAC2, KDM5B, SIRT1, RAB1A, FURIN and ADAM10) or decreased (TRIB3) virus replication. RNA-seq data revealed 14857 genes expressed in human subcutaneous adipocytes, including genes mentioned above. Irisin treatment increased by 3-fold the levels of TRIB3 transcript and decreased the levels of other genes. The decrease in FURIN and ADAM10 expression enriched diverse biological processes, including extracellular structure organization. Our results, in human subcutaneous adipocytes cell culture, indicate a positive effect of irisin on the expression of multiple genes related to viral infection by SARS-CoV-2; furthermore, translatable for other tissues and organs targeted by the novel coronavirus and present, thus, promising approaches for the treatment of COVID-19 infection as therapeutic strategy to decrease ACE2 regulatory genes.
肥胖患者由于血管紧张素转换酶 2（ACE2）在病毒感染中的作用，更容易发展为 COVID-19 重症。ACE2 在人类细胞中的表达受到与病毒复制增加（TLR3、HAT1、HDAC2、KDM5B、SIRT1、RAB1A、FURIN 和 ADAM10）或减少（TRIB3）相关的不同基因的调节。RNA-seq 数据显示，人类皮下脂肪细胞中表达了 14857 个基因，包括上述基因。鸢尾素处理使 TRIB3 转录本的水平增加了 3 倍，并降低了其他基因的水平。FURIN 和 ADAM10 表达的减少富集了多种生物学过程，包括细胞外结构组织。我们的研究结果表明，在人类皮下脂肪细胞培养物中，鸢尾素对与 SARS-CoV-2 感染相关的多个基因的表达有积极影响；此外，这些结果在其他被新型冠状病毒靶向的组织和器官中具有可翻译性，因此，为 COVID-19 感染的治疗提供了有希望的策略，可作为降低 ACE2 调节基因的治疗方法。
