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 >> Advanced Science >>article
Advanced Science

Advanced Science

IF: 14.3
Download PDF

Suppressing Mesenchymal Stromal Cell Ferroptosis Via Targeting a Metabolism-Epigenetics Axis Corrects their Poor Retention and Insufficient Healing Benefits in the Injured Liver Milieu

Published:19 February 2023 DOI: PMID: 36808838
Guangyu Hu, Zhe Cui, Xiyao Chen, Fangfang Sun, Tongzheng Li, Congye Li, Ling Zhang, Xiong Guo, Hang Zhao, Yunlong Xia, Wenjun Yan, Wei Yi, Miaomiao Fan, Rongjin Yang, Shan Wang, Ling Tao, Fuyang Zhang

Abstract

Mesenchymal stromal cell (MSC) implantation is a promising option for liver repair, but their poor retention in the injured liver milieu critically blunts therapeutic effects. The aim is to clarify the mechanisms underlying massive MSC loss post-implantation and establish corresponding improvement strategies. MSC loss primarily occurs within the initial hours after implantation into the injured liver milieu or under reactive oxygen species (ROS) stress. Surprisingly, ferroptosis is identified as the culprit for rapid depletion. In ferroptosis- or ROS-provoking MSCs, branched-chain amino acid transaminase-1 (BCAT1) is dramatically decreased, and its downregulation renders MSC susceptible to ferroptosis via suppressing the transcription of glutathione peroxidase-4 (GPX4), a vital ferroptosis defensing enzyme. BCAT1 downregulation impedes GPX4 transcription via a rapid-responsive metabolism-epigenetics coordinating mechanism, involving α-ketoglutarate accumulation, histone 3 lysine 9 trimethylation loss, and early growth response protein-1 upregulation. Approaches to suppress ferroptosis (e.g., incorporating ferroptosis inhibitors in injection solvent and overexpressing BCAT1) significantly improve MSC retention and liver-protective effects post-implantation. This study provides the first evidence indicating that excessive MSC ferroptosis is the nonnegligible culprit for their rapid depletion and insufficient therapeutic efficacy after implantation into the injured liver milieu. Strategies suppressing MSC ferroptosis are conducive to optimizing MSC-based therapy.

Substances (42)

Materials Related products
Procduct Name CAS Molecular Formula Supplier Price
Gabapentin 60142-96-3 C9H17NO2 855 suppliers $9.35-$775.00
Gabapentin 60142-96-3 C9H17NO2 855 suppliers $9.35-$775.00
Gabapentin 60142-96-3 C9H17NO2 855 suppliers $9.35-$775.00
Gabapentin 60142-96-3 C9H17NO2 855 suppliers $9.35-$775.00
2-[1-[4-[2-(4-Chlorophenoxy)acetyl]-1-piperazinyl]ethyl]-3-(2-ethoxyphenyl)-4(3H)-Quinazolinone 571203-78-6 C30H31ClN4O4 283 suppliers $16.00-$2691.10
2-[1-[4-[2-(4-Chlorophenoxy)acetyl]-1-piperazinyl]ethyl]-3-(2-ethoxyphenyl)-4(3H)-Quinazolinone 571203-78-6 C30H31ClN4O4 283 suppliers $16.00-$2691.10
2-[1-[4-[2-(4-Chlorophenoxy)acetyl]-1-piperazinyl]ethyl]-3-(2-ethoxyphenyl)-4(3H)-Quinazolinone 571203-78-6 C30H31ClN4O4 283 suppliers $16.00-$2691.10
2-[1-[4-[2-(4-Chlorophenoxy)acetyl]-1-piperazinyl]ethyl]-3-(2-ethoxyphenyl)-4(3H)-Quinazolinone 571203-78-6 C30H31ClN4O4 283 suppliers $16.00-$2691.10
Necrostatin-1 4311-88-0 C13H13N3OS 258 suppliers $12.00-$2008.00
Necrostatin-1 4311-88-0 C13H13N3OS 258 suppliers $12.00-$2008.00
抚松县| 江津市| 乌兰察布市| 白朗县| 保靖县| 珲春市| 拉萨市| 南岸区| 长春市| 新郑市| 托克逊县| 当阳市| 翁牛特旗| 祥云县| 义马市| 光山县| 宁陵县| 阳山县| 江门市| 星子县| 舟山市| 夏邑县| 东丰县| 汾西县| 涞源县| 龙陵县| 新田县| 尚志市| 建水县| 顺昌县| 平谷区| 保靖县| 北京市| 资兴市| 皮山县| 临安市| 九寨沟县| 海城市| 古丈县| 军事| 文登市|