COVID-19 is caused by the SARS-CoV-2 (SC2) virus and is more prevalent and severe in the elderly and patients with comorbid diseases (CM). Because chitinase 3-like-1 (CHI3L1) is induced during aging and CM, the relationships between CHI3L1 and SC2 were investigated. Here we demonstrate that CHI3L1 is a potent stimulator of the SC2 receptor ACE2 and viral spike protein priming proteases (SPP), that ACE2 and SPP are induced during aging and that anti-CHI3L1, kasugamycin and inhibitors of phosphorylation, abrogate these ACE2- and SPP- inductive events. Human studies also demonstrated that the levels of circulating CHI3L1 are increased in the elderly and patients with CM where they correlate with COVID-19 severity. These studies demonstrate that CHI3L1 is a potent stimulator of ACE2 and SPP; that this induction is a major mechanism contributing to the effects of aging during SC2 infection and that CHI3L1 coopts the CHI3L1 axis to augment SC2 infection. CHI3L1 plays a critical role in the pathogenesis of and is an attractive therapeutic target in COVID-19.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805436 | PMC |
| http://dx.doi.org/10.1101/2021.01.05.425478 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Chitinase-3-like-1: a multifaceted player in neuroinflammation and degenerative pathologies with therapeutic implications.
Mol Neurodegener
January 2025
Research Center for Neuroscience, Taipei Medical University, Taipei, Taiwan.
Chitinase-3-like-1 (CHI3L1) is an evolutionarily conserved protein involved in key biological processes, including tissue remodeling, angiogenesis, and neuroinflammation. It has emerged as a significant player in various neurodegenerative diseases and brain disorders. Elevated CHI3L1 levels have been observed in neurological conditions such as traumatic brain injury (TBI), Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Creutzfeldt-Jakob disease (CJD), multiple sclerosis (MS), Neuromyelitis optica (NMO), HIV-associated dementia (HAD), Cerebral ischemic stroke (CIS), and brain tumors.
View Article and Find Full Text PDFSwimming induces a physiological cardioprotection associated with pro-growth anti-inflammatory influences in extra-cardiac organs.
Am J Physiol Regul Integr Comp Physiol
December 2024
Curtin University, Curtin Medical Research Institute (Bentley, WA, AUSTRALIA).
Physical activity improves myocardial structure, function and resilience via complex, incompletely defined mechanisms. We explored effects of 1-2 wks swim training on cardiac and systemic phenotype in young male C57Bl/6 mice. Two wks forced swimming (90 min twice daily) resulted in cardiac hypertrophy (22% increase in heart:body weight, P<0.
View Article and Find Full Text PDFInflammatory Effects and Regulatory Mechanisms of Chitinase-3-like-1 in Multiple Human Body Systems: A Comprehensive Review.
Int J Mol Sci
December 2024
School of Life Sciences, Yunnan University, Kunming 650500, China.
Chitinase-3-like-1 (Chi3l1), also known as YKL-40 or BRP-39, is a highly conserved mammalian chitinase with a chitin-binding ability but no chitinase enzymatic activity. Chi3l1 is secreted by various cell types and induced by several inflammatory cytokines. It can mediate a series of cell biological processes, such as proliferation, apoptosis, migration, differentiation, and polarization.
View Article and Find Full Text PDFCHI3L1 in Multiple Sclerosis-From Bench to Clinic.
Cells
December 2024
Department of Neurology, Medical University of Lodz, Kosciuszki Street 4, 90-419 Lodz, Poland.
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) with a complex and not fully understood etiopathological background involving inflammatory and neurodegenerative processes. CHI3L1 has been implicated in pathological conditions such as inflammation, injury, and neurodegeneration, and is likely to play a role in the physiological development of the CNS. CHI3L1 is primarily produced by CNS macrophages, microglia, and activated astrocytes.
View Article and Find Full Text PDFAberrant Chitinase 3-Like 1 Expression in Basal Cells Contributes to Systemic Sclerosis Fibrosis.
Adv Sci (Weinh)
December 2024
Department of Dermatology, Zhongshan Hospital of Fudan University, Shanghai, 200032, China.
Systemic sclerosis (SSc) is an autoimmune disease characterized by extensive skin and internal organ fibrosis. However, the mechanism underlying fibrosis remains unclear, and effective treatments for halting or reversing fibrosis are lacking. In this study, single-cell RNA sequencing is used to obtain a comprehensive overview of skin cells from patients with SSc and healthy controls.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!