Extracellular Vesicle-Associated Neutrophil Elastase Activates Hepatic Stellate Cells and Promotes Liver Fibrogenesis via ERK1/2 Pathway DOI Creative Commons

Regina Oshins,

Zachary Greenberg,

Yunling Tai

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 21, 2024

Liver fibrosis associated with increased mortality is caused by activation of hepatic stellate cells and excessive production accumulation extracellular matrix in response to fibrotic insults. It has been shown that addition liver inflammation, systemic inflammation also contributes fibrogenesis. A deeper understanding mechanisms control intra- extra-hepatic essential develop novel clinical strategies against this disease. Extracellular vesicles (EV) have recognized as immune mediators facilitate cells. In inflammatory diseases, activated neutrophils release neutrophil elastase (NE) bound EV, which identified a significant contributor promoting cell activation. Here, we aimed explore the role derived plasma EV-associated NE fibrogenesis its potential mechanisms. We show induces activation, proliferation migration ERK1/2 signaling pathway. This effect did not occur through EV without surface NE, Sivelestat, inhibitor, inhibited pathway mediated NE. Moreover, found increases deposition collagen1 α-smooth muscle actin mouse model (Mdr2

Language: Английский

Extracellular Vesicle-Associated Neutrophil Elastase Activates Hepatic Stellate Cells and Promotes Liver Fibrogenesis via ERK1/2 Pathway DOI Creative Commons

Regina Oshins,

Zachary Greenberg,

Yunling Tai

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 21, 2024

Liver fibrosis associated with increased mortality is caused by activation of hepatic stellate cells and excessive production accumulation extracellular matrix in response to fibrotic insults. It has been shown that addition liver inflammation, systemic inflammation also contributes fibrogenesis. A deeper understanding mechanisms control intra- extra-hepatic essential develop novel clinical strategies against this disease. Extracellular vesicles (EV) have recognized as immune mediators facilitate cells. In inflammatory diseases, activated neutrophils release neutrophil elastase (NE) bound EV, which identified a significant contributor promoting cell activation. Here, we aimed explore the role derived plasma EV-associated NE fibrogenesis its potential mechanisms. We show induces activation, proliferation migration ERK1/2 signaling pathway. This effect did not occur through EV without surface NE, Sivelestat, inhibitor, inhibited pathway mediated NE. Moreover, found increases deposition collagen1 α-smooth muscle actin mouse model (Mdr2

Language: Английский

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