PMID- 36464837
OWN - NLM
STAT- MEDLINE
DCOM- 20230412
LR  - 20230417
IS  - 1098-2299 (Electronic)
IS  - 0272-4391 (Linking)
VI  - 84
IP  - 2
DP  - 2023 Apr
TI  - Anlotinib improves bile duct ligature-induced liver fibrosis in rats via 
      antiangiogenesis regulated by VEGFR2/mTOR pathway.
PG  - 143-155
LID - 10.1002/ddr.22019 [doi]
AB  - Cholestasis is a main clinical feature of biliary atresia (BA), which leads to 
      liver fibrosis (LF). The focus of BA treatment is preventing and slowing the 
      progress of LF. This study reports the improvement effect of anlotinib on common 
      bile duct ligature (BDL)-induced LF in young rats. The BDL young rats were 
      treated with anlotinib and the serum levels of aspartate aminotransferase, 
      alanine aminotransferase, albumin, and total bilirubin were determined. 
      Histological staining was performed and pathological changes in liver tissue were 
      observed. The expression levels of alpha-SMA, collagen I, CD31, TGF-beta1, 
      phospho-VEGFR2, phospho-4E/BP1, and phospho-S6K1 were determined. The results 
      showed that anlotinib significantly improved the liver function and 
      histopathological injury of BDL rats, inhibited the deposition of collagen and 
      hepatocyte apoptosis, and downregulated the protein expression of alpha-SMA and 
      collagen I. Furthermore, anlotinib treatment significantly inhibited 
      microvascular formation in the liver and downregulated the expression level of 
      phospho-VEGFR2, thereby suggesting that the antifibrosis effect of anlotinib may 
      be achieved by antiangiogenesis. In addition, anlotinib downregulated the 
      expression of phospho-S6K1 and upregulated the expression of phospho-4E/BP1, two 
      downstream proteins of the mammalian target of rapamycin (mTOR) pathway. MHY1485, 
      an agonist of mTOR, significantly reversed the inhibitory effect of anlotinib on 
      angiogenesis and LF but did not influence the effect of anlotinib on the 
      downregulation of phospho-VEGFR2 expression. Together, the above-mentioned 
      results suggest that the effect of anlotinib on BDL-induced LF involves at least 
      antiangiogenesis regulated by the VEGFR2/mTOR signaling pathway.
CI  - (c) 2022 Wiley Periodicals LLC.
FAU - Lei, Jun
AU  - Lei J
AD  - Department of General Surgery, Jiangxi Provincial Children's Hospital, Nanchang, 
      Jiangxi, P.R. China.
FAU - Li, Qing
AU  - Li Q
AD  - Rehabilitation Center, Jiangxi Provincial Children's Hospital, Nanchang, Jiangxi, 
      P.R. China.
FAU - Xu, Hongyan
AU  - Xu H
AD  - Department of Pathology, Jiangxi Provincial Children's Hospital, Nanchang, 
      Jiangxi, P.R. China.
FAU - Luo, Ming
AU  - Luo M
AD  - Department of General Surgery, Jiangxi Provincial Children's Hospital, Nanchang, 
      Jiangxi, P.R. China.
FAU - Liu, Zhiwen
AU  - Liu Z
AD  - Department of neonatal surgery, Jiangxi Provincial Children's Hospital, Nanchang, 
      Jiangxi, P.R. China.
FAU - Xiang, Deng
AU  - Xiang D
AD  - Department of General Surgery, Jiangxi Provincial Children's Hospital, Nanchang, 
      Jiangxi, P.R. China.
FAU - Chen, Peiqun
AU  - Chen P
AUID- ORCID: 0000-0001-7216-028X
AD  - Department of General Surgery, Jiangxi Provincial Children's Hospital, Nanchang, 
      Jiangxi, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221204
PL  - United States
TA  - Drug Dev Res
JT  - Drug development research
JID - 8204468
RN  - 0 (anlotinib)
RN  - 9007-34-5 (Collagen)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.1.1 (mTOR protein, rat)
SB  - IM
MH  - Rats
MH  - Animals
MH  - *Bile Ducts/surgery/metabolism
MH  - *Liver
MH  - Liver Cirrhosis/drug therapy/pathology
MH  - Collagen/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Mammals/metabolism
OTO - NOTNLM
OT  - VEGFR2
OT  - angiogenesis
OT  - anlotinib
OT  - biliary atresia
OT  - liver fibrosis
OT  - mTOR
EDAT- 2022/12/06 06:00
MHDA- 2023/04/12 06:42
CRDT- 2022/12/05 00:43
PHST- 2022/10/31 00:00 [revised]
PHST- 2022/05/21 00:00 [received]
PHST- 2022/11/18 00:00 [accepted]
PHST- 2023/04/12 06:42 [medline]
PHST- 2022/12/06 06:00 [pubmed]
PHST- 2022/12/05 00:43 [entrez]
AID - 10.1002/ddr.22019 [doi]
PST - ppublish
SO  - Drug Dev Res. 2023 Apr;84(2):143-155. doi: 10.1002/ddr.22019. Epub 2022 Dec 4.