Cathepsin gene expression in abdominal subcutaneous adipose tissue of obese/overweight humans

Xu, Qing; Mariman, E.C.M.; Goossens, Gijs H.; Blaak, Ellen E.; Jocken, Johan W. E.

doi:10.1080/21623945.2020.1775035

Cited by 8 publications

(14 citation statements)

References 27 publications

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“…Interestingly, CTSB and CTSL have been shown to substitute TMPRSS2 for viral entry of the Ebola virus, which affects the vasculature in the brain and in peripheral organs 100 , but their role in SARS-CoV-2 remains unknown. Whereas the expression of CTSB in the brain and in multiple peripheral tissues was previously reported 101–105, 106, 107 , the high expression of CTSB in the brain vasculature endothelium and of CTSL in the peripheral vascular endothelium at both the mRNA and protein levels was not reported to our knowledge, nor was the absence of TMPRSS2. Our own experiments revealed CTSB expression in endothelial cells, neurons, astrocytes, pericytes and microglia within the human brain neurovascular unit and might indeed provide the basis of a potential explanation for some of the putative SARS-CoV-2- mediated effects on the human blood-brain-barrier 30 as well as some of the observed neurovascular symptoms in COVID-19 patients 30, 81 .…”

Section: Discussioncontrasting

confidence: 52%

The human brain vasculature shows a distinct expression pattern of SARS-CoV-2 entry factors

Ghobrial

Charish

Takada

et al. 2020

Preprint

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A large number of hospitalized COVID-19 patients show neurological symptoms such as ischemic- and hemorrhagic stroke as well as encephalitis, and SARS-CoV-2 can directly infect endothelial cells leading to endotheliitis across multiple vascular beds. These findings suggest an involvement of the brain- and peripheral vasculature in COVID-19, but the underlying molecular mechanisms remain obscure. To understand the potential mechanisms underlying SARS-CoV-2 tropism for brain vasculature, we constructed a molecular atlas of the expression patterns of SARS-CoV-2 viral entry-associated genes (receptors and proteases) and SARS-CoV-2 interaction partners in human (and mouse) adult and fetal brain as well as in multiple non-CNS tissues in single-cell RNA-sequencing data across various datasets. We observed a distinct expression pattern of the cathepsins B (CTSB) and -L (CTSL) - which are able to substitute for the ACE2 co-receptor TMPRSS2 - in the human vasculature with CTSB being mainly expressed in the brain vasculature and CTSL predominantly in the peripheral vasculature, and these observations were confirmed at the protein level in the Human Protein Atlas and using immunofluorescence stainings. This expression pattern of SARS-CoV-2 viralentry associated proteases and SARS-CoV-2 interaction partners was also present in endothelial cells and microglia in the fetal brain, suggesting a developmentally establishedSARS-CoV-2 entry machinery in the human vasculature. At both the adult and fetal stages, we detected a distinct pattern of SARS-CoV-2 entry associated genes' transcripts in brain vascular endothelial cells and microglia, providing a potential explanation for an inflammatory response in the brain endothelium upon SARS-CoV-2 infection. Moreover, CTSB was co-expressed in adult and fetal brain endothelial cells with genes and pathways involved in innate immunity and inflammation, angiogenesis, blood-brain-barrier permeability, vascular metabolism, and coagulation, providing a potential explanation for the role of brain endothelial cells in clinically observed (neuro)vascular symptoms in COVID-19 patients. Our study serves as a publicly available single-cell atlas of SARS-CoV-2 related entry factors and interaction partners in human and mouse brain endothelial- and perivascular cells, which can be employed for future studies in clinical samples of COVID-19 patients.

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Section: Discussioncontrasting

confidence: 52%

The human brain vasculature shows a distinct expression pattern of SARS-CoV-2 entry factors

Ghobrial

Charish

Takada

et al. 2020

Preprint

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“…However, a recent study reported that CTSB mRNA expression in SCAT was unrelated with BMI or WHR but negatively correlated with whole-body insulin resistance in middle-aged individuals with obesity (age 52 ± 2 years). 17 This difference may be due to different subject characteristics (age and BMI). CTSL mRNA expression was also upregulated in the omental AT of the OB group in our study and was strongly related to CTSB mRNA expression.…”

Section: Discussionmentioning

confidence: 99%

“…Anthropometric phenotyping was performed according to a previously described method. 17 Peripheral blood was drawn in the morning after fasting for at least 8 hours for laboratory analysis, including fasting glucose levels, lipid profile and fasting insulin levels. Glucose levels, glycosylated hemoglobin (HbA1c) levels and lipid profiles including plasma triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and total cholesterol (TC) llevelswere measured using Auto-biochemical Analyzer (Olympus, Japan) by standard techniques.…”

Section: Methodsmentioning

confidence: 99%

“…This finding indicates that CTSB expression is related to markers of insulin resistance independent of adiposity, and CTSL has been reported to be related to BMI and WHR (waist/hip ratio). 17 Visceral adipose tissue is believed to play a key role in obesity-related inflammation, 18 , 19 but few studies have focused on cathepsins expression.…”

Section: Introductionmentioning

confidence: 99%

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Elevated CTSL Gene Expression Correlated with Proinflammatory Cytokines in Omental Adipose Tissue of Patients with Obesity

Zhou¹,

Zhu²,

Li³

et al. 2022

DMSO

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Purpose Cathepsin L (CTSL) and B (CTSB) were lysosomal proteases, and their expression and activity contribute to the progression of inflammation in obese rodents. Our aim was to investigate CTSB and CTSL expression in omental adipose tissue (AT) of patients with obesity and to correlate CTSB and CTSL expression with proinflammatory cytokines (CCL-2, IL-6 and IL-1β). Patients and Methods A total of 12 patients without obesity (NOB) and 51 patients with obesity (OB) were involved in this study. Omental AT was collected from all the participants for RNA extraction. Expressions of CTSB, CTSL and proinflammatory cytokines (CCL-2, IL-6 and IL-1β) were qualified with qRT-PCR. BMI (body mass index) and metabolic parameters were measured. Results The mRNA expression levels of both CTSB and CTSL were upregulated in the OB group (t = 2.693, P < 0.05; t = 2.849, P <0.01) and were related to TC levels (Std.β=0.443, P <0.05; Std.β=0.439, P <0.05). However, only the CTSB level was related to BMI (Std.β=0.261, P <0.05). In multiple regression analysis, CTSL was independently associated with CCL-2, IL-6 and IL-1β levels (Std.β=0.352–0.462, P <0.05). Conclusion CTSB and CTSL gene expressions were elevated in the omental AT of OB group. CTSL, but not CTSB, was positively correlated with proinflammatory cytokines independently, suggesting that the dysregulation of CTSL may play a significant role in the inflammatory process.

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“…Such alterations attenuate the maturation of CSTL, causing the accumulation of autophagosomes, and the consequent, suppression of autophagic clearance (Inami et al, 2011;Mizunoe et al, 2017, Mizunoe et al, 2019. Moreover, increased CTSL and decreased CTSB expression at the transcriptional level have been recently observed in abdominal subcutaneous adipose tissue of overweight/obese men and women, but further research is required to establish whether such changes impact protein levels and activity (Xu et al, 2020).…”

Section: Role Of Cathepsins and Autophagy In Obesitymentioning

confidence: 99%

Alterations in Lysosome Homeostasis in Lipid-Related Disorders: Impact on Metabolic Tissues and Immune Cells

Cabrera-Reyes

Parra-Ruiz

Yuseff

et al. 2021

Front. Cell Dev. Biol.

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Lipid-related disorders, which primarily affect metabolic tissues, including adipose tissue and the liver are associated with alterations in lysosome homeostasis. Obesity is one of the more prevalent diseases, which results in energy imbalance within metabolic tissues and lysosome dysfunction. Less frequent diseases include Niemann-Pick type C (NPC) and Gaucher diseases, both of which are known as Lysosomal Storage Diseases (LSDs), where lysosomal dysfunction within metabolic tissues remains to be fully characterized. Adipocytes and hepatocytes share common pathways involved in the lysosome-autophagic axis, which are regulated by the function of cathepsins and CD36, an immuno-metabolic receptor and display alterations in lipid diseases, and thereby impacting metabolic functions. In addition to intrinsic defects observed in metabolic tissues, cells of the immune system, such as B cells can infiltrate adipose and liver tissues, during metabolic imbalance favoring inflammation. Moreover, B cells rely on lysosomes to promote the processing and presentation of extracellular antigens and thus could also present lysosome dysfunction, consequently affecting such functions. On the other hand, growing evidence suggests that cells accumulating lipids display defective inter-organelle membrane contact sites (MCSs) established by lysosomes and other compartments, which contribute to metabolic dysfunctions at the cellular level. Overall, in this review we will discuss recent findings addressing common mechanisms that are involved in lysosome dysregulation in adipocytes and hepatocytes during obesity, NPC, and Gaucher diseases. We will discuss whether these mechanisms may modulate the function of B cells and how inter-organelle contacts, emerging as relevant cellular mechanisms in the control of lipid homeostasis, have an impact on these diseases.

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Cathepsin gene expression in abdominal subcutaneous adipose tissue of obese/overweight humans

Cited by 8 publications

References 27 publications

The human brain vasculature shows a distinct expression pattern of SARS-CoV-2 entry factors

The human brain vasculature shows a distinct expression pattern of SARS-CoV-2 entry factors

Elevated CTSL Gene Expression Correlated with Proinflammatory Cytokines in Omental Adipose Tissue of Patients with Obesity

Alterations in Lysosome Homeostasis in Lipid-Related Disorders: Impact on Metabolic Tissues and Immune Cells

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