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Therapeutic effects of selective p300 histone acetyl-transferase inhibitor on liver fibrosis

Authors
 Hyunsik Kim  ;  Soo-Yeon Park  ;  Soo Yeon Lee  ;  Jae-Hwan Kwon  ;  Seunghee Byun  ;  Mi Jeong Kim  ;  Sungryul Yu  ;  Jung-Yoon Yoo  ;  Ho-Geun Yoon  
Citation
 BMB REPORTS, Vol.56(2) : 114-119, 2023-02 
Journal Title
BMB REPORTS
ISSN
 1976-6696 
Issue Date
2023-02
MeSH
Animals ; Diet, High-Fat ; Disease Models, Animal ; Histones* / metabolism ; Liver / metabolism ; Liver Cirrhosis* ; Mice ; Subst
Abstract
Liver fibrosis is caused by chronic liver damage and results in the aberrant accumulation of extracellular matrix during disease progression. Despite the identification of the HAT enzyme p300 as a major factor for liver fibrosis, the development of therapeutic agents targeting the regulation of p300 has not been reported. We validated a novel p300 inhibitor (A6) on the improvement of liver fibrosis using two mouse models, mice on a choline-deficient high-fat diet and thioacetamide-treated mice. We demonstrated that pathological hall-marks of liver fibrosis were significantly diminished by A6 treatment through Masson's trichrome and Sirius red staining on liver tissue and found that A6 treatment reduced the expression of matricellular protein genes. We further showed that A6 treatment improved liver fibrosis by reducing the stability of p300 protein via disruption of p300 binding to AKT. Our findings suggest that targeting p300 through the specific inhibitor A6 has potential as a major therapeutic avenue for treating liver fibrosis. [BMB Reports 2023; 56(2): 114-119].
Files in This Item:
T202301602.pdf Download
DOI
10.5483/BMBRep.2022-0188
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Park, Soo Yeon(박수연) ORCID logo https://orcid.org/0000-0003-3743-9554
Yoo, Jung Yoon(유정윤) ORCID logo https://orcid.org/0000-0001-9366-3863
Yoon, Ho Geun(윤호근) ORCID logo https://orcid.org/0000-0003-2718-3372
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/193693
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