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Endothelial p300 Promotes Portal Hypertension and Hepatic Fibrosis Through C‐C Motif Chemokine Ligand 2–Mediated Angiocrine Signaling by Gao, Jinhang; Wei, Bo; Liu, Mengfei; Hirsova, Petra; Sehrawat, Tejasav S.; Cao, Sheng; Hu, Xiao; Xue, Fei; Yaqoob, Usman; Kang, Ningling; Cui, Huarui; Pomerantz, William C.K.; Kostallari, Enis; Shah, Vijay H. is a Medicine article available to read on EtoBox.

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## 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 CCl~4~ 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 of inflammation regulation. Leukocytes were analyzed by mass cytometry by time‐of‐flight. Epigenetic histone marks were modified by CRISPR endonuclease‐deficient CRISPR‐associated 9‐fused with the Krüppel associated box domain (CRISPR‐dCas9‐KRAB)–mediated epigenome editing. Portal pressure and liver fibrosis were reduced in p300 ^LSECΔ/Δ^ mice compared to p300 ^fl/fl^ mice following liver injury. Accumulation of macrophages

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Author

Gao, Jinhang; Wei, Bo; Liu, Mengfei; Hirsova, Petra; Sehrawat, Tejasav S.; Cao, Sheng; Hu, Xiao; Xue, Fei; Yaqoob, Usman; Kang, Ningling; Cui, Huarui; Pomerantz, William C.K.; Kostallari, Enis; Shah, Vijay H.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Published

2020

Language

EN

Field

Medicine (Health Sciences)