FLI1 and ERG protein degradation is regulated via Cathepsin B lysosomal pathway in human dermal microvascular endothelial cells.
Cathepsin B
ERG
FLI1
endothelial cells
scleroderma
Journal
Microcirculation (New York, N.Y. : 1994)
ISSN: 1549-8719
Titre abrégé: Microcirculation
Pays: United States
ID NLM: 9434935
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
27
05
2020
revised:
11
07
2020
accepted:
16
09
2020
pubmed:
27
9
2020
medline:
9
11
2021
entrez:
26
9
2020
Statut:
ppublish
Résumé
Friend leukemia integration 1 and erythroblast transformation-specific, important regulators of endothelial cell homeostasis, are reduced in microvascular endothelial cells in scleroderma patients, and their deficiency has been implicated in disease pathogenesis. The goal of this study was to identify the mechanisms involved in the protein turnover of friend leukemia integration 1 and erythroblast transformation-specific in microvascular endothelial cells. The effects of lysosome and proteosome inhibitors on friend leukemia integration 1 and erythroblast transformation-specific levels were assessed by Western blotting and capillary morphogenesis. The effect of scleroderma and control sera on the levels of friend leukemia integration 1 and erythroblast transformation-specific was examined. The reduction in the protein levels of friend leukemia integration 1 and erythroblast transformation-specific in response to interferon α or Poly:(IC) was reversed by blocking either lysosomal (leupeptin and Cathepsin B inhibitor) or proteosomal degradation (MG132). MG132, leupeptin or CTSB-(i) also counteracted the anti-angiogenic effects of Poly:(IC) or interferon α. Scleroderma sera reduced protein levels of friend leukemia integration 1 and erythroblast transformation-specific in comparison to control sera. Treatment with CTSB(i) increased the levels of friend leukemia integration 1 and erythroblast transformation-specific in a majority of serum-treated samples. Inhibition of cathepsin B was effective in reversing the reduction of friend leukemia integration 1 and erythroblast transformation-specific protein levels after treatment with interferon α or scleroderma sera, suggesting that targeting cathepsin B may have a beneficial effect in SSc vascular disease.
Identifiants
pubmed: 32979864
doi: 10.1111/micc.12660
pmc: PMC7988617
doi:
Substances chimiques
ERG protein, human
0
FLI1 protein, human
0
Proto-Oncogene Protein c-fli-1
0
Transcriptional Regulator ERG
0
CTSB protein, human
EC 3.4.22.1
Cathepsin B
EC 3.4.22.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12660Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR044883
Pays : United States
Informations de copyright
© 2020 The Authors. Microcirculation published by John Wiley & Sons Ltd.
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