2022
DOI: 10.1016/j.jcmgh.2021.08.004
|View full text |Cite
|
Sign up to set email alerts
|

SYK-3BP2 Pathway Activity in Parenchymal and Myeloid Cells Is a Key Pathogenic Factor in Metabolic Steatohepatitis

Abstract: This work reports that SYK-3BP2 pathway activity enhances the LPS-TLR4 responses in both hepatocytes and resident liver macrophages. This initiates the onset of local inflammation and contributes to liver accumulation of leukocytes. Targeting of 3BP2 or SYK prevents metabolic steatohepatitis features.BACKGROUND & AIMS: Spleen tyrosine kinase (SYK) signaling pathway regulates critical processes in innate immunity, but its role in parenchymal cells remains elusive in chronic liver diseases. We investigate the re… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
1
1
1
1

Citation Types

0
5
0

Year Published

2022
2022
2024
2024

Publication Types

Select...
5
1

Relationship

1
5

Authors

Journals

citations
Cited by 6 publications
(5 citation statements)
references
References 67 publications
0
5
0
Order By: Relevance
“…In the adult population, NASH, the progressive form of MAFLD, is the consequence of abnormal activation of liver conventional immune, endothelial and parenchymal cells by inflammatory mediators from the gut, adipose tissue (AT) and liver. The secretion of inflammatory mediators by hepatocytes, resident macrophages (Kupffer cells) and liver sinusoidal endothelial cells, for example, strongly contributes to the substantial liver accumulation of neutrophils and bone-marrow-derived macrophages [ 19 , 20 ]. However, this pathogenic event is less clear in children.…”
Section: General Information On Pediatric Mafldmentioning
confidence: 99%
“…In the adult population, NASH, the progressive form of MAFLD, is the consequence of abnormal activation of liver conventional immune, endothelial and parenchymal cells by inflammatory mediators from the gut, adipose tissue (AT) and liver. The secretion of inflammatory mediators by hepatocytes, resident macrophages (Kupffer cells) and liver sinusoidal endothelial cells, for example, strongly contributes to the substantial liver accumulation of neutrophils and bone-marrow-derived macrophages [ 19 , 20 ]. However, this pathogenic event is less clear in children.…”
Section: General Information On Pediatric Mafldmentioning
confidence: 99%
“…31 SYK is a cytoplasmic nonreceptor tyrosine kinase, and its overexpression has been detected in balloon hepatocytes containing Mallory−Denk bodies, a hallmark of chronic liver diseases such as metabolism-associated fatty liver diseases and alcoholic liver diseases. 32 Besides, SYK is capable of facilitating liver fibrosis. 33 Specifically, SYK is also confirmed as the hub gene implicated in NASH.…”
Section: Discussionmentioning
confidence: 99%
“…Recently, scientists discovered another SYK-related ITAM-containing adaptor, 3BP2. Both 3BP2 and SYK correlate with severity of steatohepatitis, indicating that functional adaptor protein for SYK could be varied in different tissues [ 24 ].…”
Section: Characterization and Origin Of Syk In Livermentioning
confidence: 99%
“…demonstrated that an ITAM-containing adaptor, 3BP2, is also related with SYK function in steatohepatitis. SYK in myeloid cells strongly suppresses the recruitment of infiltrating neutrophils and macrophages into the liver, and either 3BP2 deficiency or SYK deletion in myeloid cells shows therapeutic effects against liver inflammation, indicating the important position of SYK-3BP2 signaling pathway in the development of liver inflammatory diseases [ 24 ].…”
Section: The Relationship Between Syk and Different Liver Diseasesmentioning
confidence: 99%