PMID- 37494836
OWN - NLM
STAT- MEDLINE
DCOM- 20230927
LR  - 20230927
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 123
DP  - 2023 Oct
TI  - Human umbilical cord-derived mesenchymal stromal cells alleviate liver cirrhosis 
      through the Hippo/YAP/Id1 pathway and macrophage-dependent mechanism.
PG  - 110456
LID - S1567-5769(23)00779-8 [pii]
LID - 10.1016/j.intimp.2023.110456 [doi]
AB  - BACKGROUND: Few effective anti-fibrotic therapies are currently available for 
      liver cirrhosis. Mesenchymal stromal cells (MSCs) ameliorate liver fibrosis and 
      contribute to liver regeneration after cirrhosis, attracting much attention as a 
      potential therapeutic strategy for the disease. However, the underlying molecular 
      mechanism of their therapeutic effect is still unclear. Here, we investigated the 
      effect of human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs) in 
      treating liver cirrhosis and their underlying mechanisms. METHODS: We used carbon 
      tetrachloride (CCl(4))-induced mice as liver cirrhosis models and treated them 
      with hUC-MSCs via tail vein injection. We assessed the changes in liver function, 
      inflammation, and fibrosis by histopathology and serum biochemistry and explored 
      the mechanism of hUC-MSCs by RNA sequencing (RNA-seq) using liver tissues. In 
      addition, we investigated the effects of hUC-MSCs on hepatic stellate cells (HSC) 
      and macrophages by in vitro co-culture experiments. RESULTS: We found that 
      hUC-MSCs considerably improved liver function and attenuated liver inflammation 
      and fibrosis in CCl(4)-injured mice. We also showed that these cells exerted 
      therapeutic effects by regulating the Hippo/YAP/Id1 axis in vivo. Our in vitro 
      experiments demonstrated that hUC-MSCs inhibit HSC activation by regulating the 
      Hippo/YAP signaling pathway and targeting Id1. Moreover, hUC-MSCs also alleviated 
      liver inflammation by promoting the transformation of macrophages to an 
      anti-inflammatory phenotype. CONCLUSIONS: Our study reveals that hUC-MSCs relieve 
      liver cirrhosis in mice through the Hippo/YAP/Id1 pathway and 
      macrophage-dependent mechanisms, providing a theoretical basis for the future use 
      of these cells as a potential therapeutic strategy for patients with liver 
      cirrhosis.
CI  - Copyright (c) 2023. Published by Elsevier B.V.
FAU - Yao, Lichao
AU  - Yao L
AD  - Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan 
      430060, People's Republic of China.
FAU - Hu, Xue
AU  - Hu X
AD  - Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan 
      430060, People's Republic of China.
FAU - Yuan, Mengqin
AU  - Yuan M
AD  - Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan 
      430060, People's Republic of China.
FAU - Liu, Pingji
AU  - Liu P
AD  - Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan 
      430060, People's Republic of China.
FAU - Zhang, Qiuling
AU  - Zhang Q
AD  - Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan 
      430060, People's Republic of China.
FAU - Wang, Zheng
AU  - Wang Z
AD  - Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan 
      430060, People's Republic of China.
FAU - Chen, Ping
AU  - Chen P
AD  - Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan 
      430060, People's Republic of China.
FAU - Xiong, Zhiyu
AU  - Xiong Z
AD  - Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan 
      430060, People's Republic of China.
FAU - Wu, Lun
AU  - Wu L
AD  - Experiment Center of Medicine, Sinopharm Dongfeng General Hospital, Hubei 
      University of Medicine, Shiyan 442008, People's Republic of China. Electronic 
      address: wulun0909@163.com.
FAU - Dai, Kai
AU  - Dai K
AD  - Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan 
      430060, People's Republic of China. Electronic address: daikai@whu.edu.cn.
FAU - Jiang, Yingan
AU  - Jiang Y
AD  - Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan 
      430060, People's Republic of China. Electronic address: jiangya_cn@aliyun.com.
LA  - eng
PT  - Journal Article
DEP - 20230724
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (YAP-Signaling Proteins)
RN  - 0 (Inhibitor of Differentiation Protein 1)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Mice
MH  - Fibrosis
MH  - Inflammation/metabolism
MH  - Liver Cirrhosis/chemically induced/therapy/metabolism
MH  - Macrophages/metabolism
MH  - *Mesenchymal Stem Cell Transplantation
MH  - *Mesenchymal Stem Cells/metabolism
MH  - Umbilical Cord
MH  - Hippo Signaling Pathway
MH  - YAP-Signaling Proteins/metabolism
MH  - Inhibitor of Differentiation Protein 1/metabolism
OTO - NOTNLM
OT  - Hepatic stellate cells
OT  - Hippo/YAP
OT  - Human umbilical cord-derived mesenchymal stromal cells
OT  - Liver cirrhosis
OT  - Macrophages
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/07/27 01:09
MHDA- 2023/09/22 06:42
CRDT- 2023/07/26 18:04
PHST- 2023/04/13 00:00 [received]
PHST- 2023/05/28 00:00 [revised]
PHST- 2023/06/02 00:00 [accepted]
PHST- 2023/09/22 06:42 [medline]
PHST- 2023/07/27 01:09 [pubmed]
PHST- 2023/07/26 18:04 [entrez]
AID - S1567-5769(23)00779-8 [pii]
AID - 10.1016/j.intimp.2023.110456 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2023 Oct;123:110456. doi: 10.1016/j.intimp.2023.110456. Epub 
      2023 Jul 24.