PMID- 31162246
OWN - NLM
STAT- MEDLINE
DCOM- 20200518
LR  - 20211204
IS  - 1533-4023 (Electronic)
IS  - 0160-2446 (Linking)
VI  - 73
IP  - 6
DP  - 2019 Jun
TI  - Puerarin Decreases Collagen Secretion in AngII-Induced Atrial Fibroblasts Through 
      Inhibiting Autophagy Via the JNK-Akt-mTOR Signaling Pathway.
PG  - 373-382
LID - 10.1097/FJC.0000000000000672 [doi]
AB  - Puerarin is used to treat cardiovascular diseases due to its anti-inflammatory 
      and antifibrotic effects. However, its mechanism of action in atrial fibroblasts 
      is unknown. In this study, we investigated the autophagy pathway and molecular 
      changes in angiotensin II (AngII)-stimulated atrial fibroblasts in response to 
      puerarin treatment. Atrial fibroblasts were cultured and then subjected to 
      stimulation with AngII and puerarin or other chemical drugs (3-MA, CQ, and 
      SP600125). Quantitative real-time polymerase chain reaction and Western blot 
      experiments were used to quantify the expression levels of mRNA and protein. 
      mCherry-GFP-LC3 adenovirus was applied to reflect the autophagic flux. The 
      results showed aggravating levels of autophagy and collagen deposit in the 
      presence of AngII. Puerarin inhibited autophagy and decreased collagen secretion 
      in a dose-dependent manner in atrial fibroblasts. Furthermore, phosphorylation of 
      JNK was down-regulated in response to puerarin, whereas phosphorylation of Akt 
      and mammalian target of rapamycin (mTOR) was upregulated. Interestingly, reduced 
      autophagy and collagen secretion were observed when the JNK signaling pathway was 
      blocked using SP600125. We also observed upregulation of Akt and mTOR 
      phosphorylation in the presence of SP600125. These results suggest that puerarin 
      exerts its antifibrotic effect in atrial fibroblasts partly through the 
      inhibition of autophagy. Furthermore, the mechanism of action of puerarin in 
      fibroblast autophagy seems to be mediated partly through JNK-Akt-mTOR signaling.
FAU - Xu, Xudong
AU  - Xu X
AD  - Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School 
      of Medicine, Hangzhou, China.
FAU - Jiang, Ruhong
AU  - Jiang R
FAU - Chen, Mengmeng
AU  - Chen M
FAU - Dong, Mengmeng
AU  - Dong M
FAU - Liu, Qiang
AU  - Liu Q
FAU - Cheng, Hui
AU  - Cheng H
FAU - Zhou, Kuangshi
AU  - Zhou K
FAU - Chen, Laite
AU  - Chen L
FAU - Li, Miaomiao
AU  - Li M
FAU - Jiang, Chenyang
AU  - Jiang C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cardiovasc Pharmacol
JT  - Journal of cardiovascular pharmacology
JID - 7902492
RN  - 0 (Cardiovascular Agents)
RN  - 0 (Isoflavones)
RN  - 11128-99-7 (Angiotensin II)
RN  - 9007-34-5 (Collagen)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - Z9W8997416 (puerarin)
SB  - IM
MH  - Angiotensin II/*toxicity
MH  - Animals
MH  - Autophagy/*drug effects
MH  - Cardiovascular Agents/*pharmacology
MH  - Cells, Cultured
MH  - Collagen/genetics/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Fibroblasts/*drug effects/enzymology/pathology
MH  - Fibrosis
MH  - Heart Atria/*drug effects/enzymology/pathology
MH  - Isoflavones/*pharmacology
MH  - JNK Mitogen-Activated Protein Kinases/*metabolism
MH  - Mice
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Time Factors
EDAT- 2019/06/05 06:00
MHDA- 2020/05/19 06:00
CRDT- 2019/06/05 06:00
PHST- 2019/06/05 06:00 [entrez]
PHST- 2019/06/05 06:00 [pubmed]
PHST- 2020/05/19 06:00 [medline]
AID - 00005344-201906000-00005 [pii]
AID - 10.1097/FJC.0000000000000672 [doi]
PST - ppublish
SO  - J Cardiovasc Pharmacol. 2019 Jun;73(6):373-382. doi: 
      10.1097/FJC.0000000000000672.