一二三四区视频,亚洲少妇熟女色,日本久热无码视频网,欧美国产日韩大尺度,亚洲a视频,久久少妇一区二区,日韩999无码视频,刺激久久久久久久,啊啊啊啊不要啊在线

ChemicalBook >> journal list >> MedComm >>article

MedComm

IF: 10.7
Download PDF

Cellular senescence primes liver fibrosis regression through Notch-EZH2

Published:21 August 2023 DOI: 10.1002/mco2.346 PMID: 37614965
Ping Song, Juan-Li Duan, Jian Ding, Jing-Jing Liu, Zhi-Qiang Fang, Hao Xu, Zhi-Wen Li, Wei Du, Ming Xu, Yu-Wei Ling, Fei He, Kai-Shan Tao, Lin Wang

Abstract

Cellular senescence plays a pivotal role in wound healing. At the initiation of liver fibrosis regression, accumulated senescent cells were detected and genes of senescence were upregulated. Flow cytometry combined with single-cell RNA sequencing analyses revealed that most of senescent cells were liver nonparenchymal cells. Removing senescent cells by dasatinib and quercetin (DQ), alleviated hepatic cellular senescence, impeded fibrosis regression, and disrupted liver sinusoids. Clearance of senescent cells not only decreased senescent macrophages but also shrank the proportion of anti-inflammatory M2 macrophages through apoptotic pathway. Subsequently, macrophages were depleted by clodronate, which diminished hepatic senescent cells and impaired fibrosis regression. Mechanistically, the change of the epigenetic regulator enhancer of zeste homolog2 (EZH2) accompanied with the emergence of hepatic senescent cells while liver fibrosis regressed. Blocking EZH2 signaling by EPZ6438 reduced hepatic senescent cells and macrophages, decelerating liver fibrosis regression. Moreover, the promoter region of EZH2 was transcriptionally suppressed by Notch-Hes1 (hairy and enhancer of split 1) signaling. Disruption of Notch in macrophages using Lyz2 (lysozyme 2) Cre-RBP-J (recombination signal binding protein Jκ) f/f transgenic mice, enhanced hepatic cellular senescence, and facilitated fibrosis regression by upregulating EZH2 and blocking EZH2 abrogated the above effects caused by Notch deficiency. Ultimately, adopting Notch inhibitor Ly3039478 or exosome-mediated RBP-J decoy oligodeoxynucleotides accelerated liver fibrosis regression by augmenting hepatic cellular senescence.

Substances (5)

Materials Related products
Procduct Name CAS Molecular Formula Supplier Price
Tazemetostat 1403254-99-8 C34H44N4O4 241 suppliers $9.00-$2062.50
Tazemetostat 1403254-99-8 C34H44N4O4 241 suppliers $9.00-$2062.50
Tazemetostat 1403254-99-8 C34H44N4O4 241 suppliers $9.00-$2062.50
Tazemetostat 1403254-99-8 C34H44N4O4 241 suppliers $9.00-$2062.50

Similar articles

IF:6.7

Pharmacokinetics and anti-liver fibrosis characteristics of amygdalin: Key role of the deglycosylated metabolite prunasin

Phytomedicine Congcong Zhang , Dingqi Zhang ,etc Published: 1 May 2022
IF:5.3

Cellular and molecular pharmacology of oxaliplatin.

Molecular Cancer Therapeutics Eric Raymond, Sandrine Faivre,etc Published: 1 January 2002
IF:6.1

Systemic tumor regression with synergy therapy: radiotherapy and CAR-T

Cell Death Discovery Ma, Xingyu,etc Published: 22 November 2024
连平县| 富川| 宣汉县| 凤台县| 峨山| 昌邑市| 大邑县| 旬阳县| 磐安县| 阳山县| 鄂托克前旗| 云浮市| 景泰县| 宕昌县| 东源县| 安国市| 南华县| 龙南县| 永昌县| 恩施市| 金塔县| 呈贡县| 林西县| 凤凰县| 嘉义县| 启东市| 厦门市| 云南省| 孝感市| 临城县| 沁水县| 仪征市| 宣化县| 霍邱县| 长沙县| 南漳县| 济源市| 平原县| 樟树市| 德庆县| 星子县|