The Potential Role of Osteopontin and Furin in Worsening Disease Outcomes in COVID-19 Patients with Pre-Existing Diabetes

Cells

AlexanderG. Obukhov¹  Yvonne Adu-Agyeiwaah²  MariaB. Grant² 

[1] Department of Anatomy, Cell Biology & Physiology, The Indiana University School of Medicine, Indiana University, Indianapolis, IN 46202, USA;Department of Ophthalmology and Visual Sciences, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA;

关键词: coronavirus;    osteopontin;    furin;    diabetes;    ACE2;   

DOI  :  10.3390/cells9112528

来源: DOAJ

【 摘 要 】

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the ongoing coronavirus disease 2019 (COVID-19) pandemic, with more than 50 million cases reported globally. Findings have consistently identified an increased severity of SARS-CoV-2 infection in individuals with diabetes. Osteopontin, a cytokine-like matrix-associated phosphoglycoprotein, is elevated in diabetes and drives the expression of furin, a proprotein convertase implicated in the proteolytic processing and activation of several precursors, including chemokines, growth factors, hormones, adhesion molecules, and receptors. Elevated serum furin is a signature of diabetes mellitus progression and is associated with a dysmetabolic phenotype and increased risk of diabetes-linked premature mortality. Additionally, furin plays an important role in enhancing the infectivity of SARS-CoV-2 by promoting its entry and replication in the host cell. Here, we hypothesize that diabetes-induced osteopontin and furin protein upregulation results in worse outcomes in diabetic patients with SARS-CoV-2 infection owing to the roles of these protein in promoting viral infection and increasing metabolic dysfunction. Thus, targeting the osteopontin-furin axis may be a plausible strategy for reducing mortality in SARS-CoV-2 patients with diabetes.

【 授权许可】

Unknown