PMID- 34692767
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211026
IS  - 2296-889X (Print)
IS  - 2296-889X (Electronic)
IS  - 2296-889X (Linking)
VI  - 8
DP  - 2021
TI  - Folic Acid Alleviates High Glucose and Fat-Induced Pyroptosis via Inhibition of 
      the Hippo Signal Pathway on H9C2 Cells.
PG  - 698698
LID - 10.3389/fmolb.2021.698698 [doi]
LID - 698698
AB  - Diabetic cardiomyopathy (DCM) is the leading cause of death in diabetic patients. 
      Folic acid has a protective effect on diabetes-induced cardiomyocyte damage. The 
      aim of this study was to explore the effects of folic acid on cardiomyocytes 
      cultured under high glucose and fat (HGF) conditions and type 2 diabetes mellitus 
      (T2DM) mice, and elucidate the underlying mechanisms. Bioinformatics analysis was 
      used to identify the potential drugs through the Drug-Gene Interaction database. 
      H9C2 cardiomyocytes were cultured with 30 mM glucose and 500 nM palmitic acid in 
      the presence or absence of folic acid or YAP1 inhibitor (verteporfin) or YAP1 
      siRNA. The cell viability and lactate dehydrogenase (LDH) release were measured 
      using specific assay kits. Pyroptosis was detected by flow cytometry. The 
      concentrations of IL-1beta and IL-18 in the supernatants were measured by ELISA. The 
      NLRP3, ASC and caspase-1 mRNA levels were detected by qRT-PCR and that the 
      proteins expression of NLRP3, ASC, cleaved caspase-1 (p10), caspase-1, YAP1, 
      p-YAP1, LATS1 and P-LATS1 were detected by Western blotting. C57BL/6 mice were 
      fed with high fat diet (HFD) combined with streptozotocin (STZ) intraperitoneally 
      to establish a T2DM model, folic acid or PBS treatment for 8 weeks by oral 
      gavage, blood glucose and body weight were measured every 4 weeks, mouse heart 
      tissue was used to detect pyroptosis and hippo signaling pathway related protein 
      expression. We identified 427 differentially expressed genes in the cardiac 
      tissues of high fat diet + streptozotocin mice, among the 30 most significantly 
      DEGs, folic acid was predicted to be the most likely therapeutic drug. Folic acid 
      alleviated HGF-induced cell damage in vitro and in vivo by decreasing activation 
      of the Hippo pathway, as indicated by lower LDH release and increased cell 
      viability, and decreased expression of NLRP3, ASC, cleaved caspase-1, IL-1beta, 
      IL-18, p-YAP and p-LATS. Verteporfin or YAP1 siRNA neutralized the protective 
      effect of folic acid by reversing YAP1-induced pyroptosis. Folic acid reduced 
      NLRP3 inflammasome-mediated pyroptosis by down-regulating the Hippo signaling 
      pathway, thereby effectively reducing T2DM-induced damage in H9C2 cells and 
      animals.
CI  - Copyright (c) 2021 Hong, Zha, Wang, Qiao and An.
FAU - Hong, Lei
AU  - Hong L
AD  - Institute of Clinical Medicine Research, Affiliated Suzhou Science and Technology 
      Town Hospital of Nanjing Medical University, Suzhou, China.
FAU - Zha, Yingjie
AU  - Zha Y
AD  - Institute of Clinical Medicine Research, Affiliated Suzhou Science and Technology 
      Town Hospital of Nanjing Medical University, Suzhou, China.
FAU - Wang, Chen
AU  - Wang C
AD  - Department of Anesthesiology, Affiliated Suzhou Science and Technology Town 
      Hospital of Nanjing Medical University, Suzhou, China.
FAU - Qiao, Shigang
AU  - Qiao S
AD  - Department of Anesthesiology, Affiliated Suzhou Science and Technology Town 
      Hospital of Nanjing Medical University, Suzhou, China.
FAU - An, Jianzhong
AU  - An J
AD  - Institute of Clinical Medicine Research, Affiliated Suzhou Science and Technology 
      Town Hospital of Nanjing Medical University, Suzhou, China.
LA  - eng
PT  - Journal Article
DEP - 20211007
PL  - Switzerland
TA  - Front Mol Biosci
JT  - Frontiers in molecular biosciences
JID - 101653173
PMC - PMC8529044
OTO - NOTNLM
OT  - diabetic cardiomyopathy
OT  - folic acid
OT  - hippo signal pathway
OT  - pyroptosis
OT  - type 2 diabetes
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/10/26 06:00
MHDA- 2021/10/26 06:01
PMCR- 2021/01/01
CRDT- 2021/10/25 06:39
PHST- 2021/04/22 00:00 [received]
PHST- 2021/09/17 00:00 [accepted]
PHST- 2021/10/25 06:39 [entrez]
PHST- 2021/10/26 06:00 [pubmed]
PHST- 2021/10/26 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 698698 [pii]
AID - 10.3389/fmolb.2021.698698 [doi]
PST - epublish
SO  - Front Mol Biosci. 2021 Oct 7;8:698698. doi: 10.3389/fmolb.2021.698698. 
      eCollection 2021.