Endothelial p300 Promotes Portal Hypertension and Hepatic Fibrosis Through C-C Motif Chemokine Ligand 2-Mediated Angiocrine Signaling.

ABSTRACT:

Background and aims

During liver fibrosis, liver sinusoidal endothelial cells (LSECs) release angiocrine signals to recruit inflammatory cells into the liver. p300, a master regulator of gene transcription, is associated with pathological inflammatory response. Therefore, we examined how endothelial p300 regulates angiocrine signaling and inflammation related to portal hypertension and fibrogenesis.

Approach and results

CCl₄ or partial inferior vena cava ligation (pIVCL) was used to induce liver injury. Mice with LSEC-specific p300 deletion (p300^LSECΔ/Δ ) or C-C motif chemokine ligand 2 (Ccl2) deficiency, nuclear factor kappa B (NFκB)-p50 knockout mice, and bromodomain containing 4 (BRD4) inhibitors in wild-type mice were used to investigate mechanisms

SUBMITTER: Gao J 

PROVIDER: S-EPMC8102654 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature