Dataset Information

Identification of the proteins secreted by normal and cirrhotic LSECs

ABSTRACT: Normal and cirrhotic LSECs can influence hepatic stellate cells (HSCs) differently. This project aims to determine the set of proteins secreted by LSECs from healthy and cirrhotic livers, and identify the protein(s) that promote HSC activation.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Liver, Cell Culture, Endothelial Cell

DISEASE(S): Liver Cirrhosis

SUBMITTER: Ana Maretti-Mira

LAB HEAD: Laurie D. DeLeve

PROVIDER: PXD009010 | Pride | 2018-11-06

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

Items per page:

1 - 5 of 12

Publications

Incomplete Differentiation of Engrafted Bone Marrow Endothelial Progenitor Cells Initiates Hepatic Fibrosis in the Rat.

Maretti-Mira Ana C AC Wang Xiangdong X Wang Lei L DeLeve Laurie D LD

Hepatology (Baltimore, Md.) 20190207 3

Normal liver sinusoidal endothelial cells (LSECs) promote quiescence of hepatic stellate cells (HSCs). Prior to fibrosis, LSECs undergo capillarization, which is permissive for HSC activation, the proximate event in hepatic fibrosis. The aims of this study were to elucidate the nature of and mechanisms leading to capillarization and to determine how LSECs promote HSC quiescence and why "capillarized LSECs" lose control of HSC activation. The contribution of bone marrow (BM) endothelial progenito ...[more]

PMID: 30141211

Similar Datasets

Project description:Background & Aims: NOTCH signaling in liver sinusoidal endothelial cells (LSECs) regulates liver fibrosis, a pathological feature of chronic liver diseases. POFUT1 is an essential regulator of NOTCH signaling. Here, we investigated the role of LSECs-expressed POFUT1 in liver fibrosis. Methods: Endothelial-specific Pofut1 knockout mice were generated and subjected to experimental liver fibrosis by chronic carbon tetrachloride exposure or by common bile duct ligation. Liver samples were assessed by ELISA, histology, electron microscopy, immunostaining and RNA in situ hybridization. LSECs and hepatic stellate cells (HSCs) were isolated for gene expression analysis by RNA-seq, qPCR, and Western blotting. Signaling crosstalk between LSECs and HSCs was investigated by treating HSCs with supernatant from LSECs cultures. Liver single-cell RNA-seq data sets from cirrhotic patients and healthy individuals were analyzed to evaluate the clinical relevance of gene expression changes observed in mouse studies. Results: POFUT1 loss promoted injury-induced LSECs capillarization and HSC activation, leading to aggravated liver fibrosis. RNA-seq analysis revealed that POFUT1 deficiency upregulated fibrinogen expression in LSECs. Consistently, fibrinogen was elevated in LSECs of cirrhotic patients. HSCs treated with supernatant from LSECs of Pofut1 null mice showed exacerbated activation compared to treatment with supernatant from control LSECs, and this effect was attenuated by knockdown of fibrinogen or by pharmacological inhibition of fibrinogen receptor signaling, altogether suggesting that LSEC-derived fibrinogen induced the activation of HSCs. Mechanistically, POFUT1 loss augmented fibrinogen expression by enhancing NOTCH/HES1/STAT3 signaling. Conclusions: Endothelial POFUT1 prevents injury-induced liver fibrosis by repressing the expression of fibrinogen which function as a profibrotic paracrine signal to activate HSCs. Therapies targeting the POFUT1/NOTCH/HES1/STAT3/fibrinogen axis offer a promising strategy for the prevention and treatment of fibrotic liver diseases.

			Action	DRS
	Wang_TAA_1_1027.mgf	Mgf
	Wang_TAA_1_1027.mzid	Mzid
	Wang_TAA_1_1027.raw	Raw
	Wang_TAA_2_1027.mgf	Mgf
	Wang_TAA_2_1027.mzid	Mzid