PMID- 31486509
OWN - NLM
STAT- MEDLINE
DCOM- 20201207
LR  - 20201214
IS  - 2284-0729 (Electronic)
IS  - 1128-3602 (Linking)
VI  - 23
IP  - 16
DP  - 2019 Aug
TI  - Effect of miR-26a targeting GSK-3beta/beta-catenin signaling pathway on myocardial 
      apoptosis in rats with myocardial ischemia-reperfusion.
PG  - 7073-7082
LID - 18751 [pii]
LID - 10.26355/eurrev_201908_18751 [doi]
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of micro ribonucleic 
      acid (miR)-26a on myocardial ischemia-reperfusion (I/R) injury in rats and to 
      explore its potential mechanism. Our findings might help to provide references 
      for clinical prevention and treatment of myocardial I/R. MATERIALS AND METHODS: A 
      total of 60 male Sprague-Dawley (SD) rats were randomly divided into three groups 
      using a random number table, including: Control group (n=20), I/R group (n=20) 
      and I/R + miR-26a siRNA group (n=20). I/R model was established via 
      recanalization after ligation of left anterior descending coronary artery (LAD). 
      The model of miR-26a knockdown was established in rats of I/R + miR-26a siRNA 
      group via tail intravenous injection of miR-26a siRNA. Ejection fraction (EF%) 
      and fractional shortening (FS%) of rats in each group were detected via 
      echocardiography. The infarction area of each group was detected via 
      2,3,5-triphenyltetrazolium chloride (TTC) assay. Subsequently, morphological 
      changes in myocardial cells of each group were detected via hematoxylin-eosin 
      (H&E) staining. Myocardial apoptosis level was measured via terminal 
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. At 
      the same time, the expression levels of pro-apoptotic proteins Bcl-2 associated X 
      protein (Bax) and cleaved (C)-caspase3 in myocardial tissues of the three groups 
      were determined using Western blotting. Finally, the effects of miR-26a knockdown 
      on the expressions of glycogen synthase kinase (GSK)-3beta/beta-catenin signaling 
      pathway-related proteins were detected via Western blotting and 
      immunohistochemistry. RESULTS: The expression of miR-26a in myocardial tissues of 
      I/R group increased significantly when compared with that in Control group 
      (p<0.05). Knockdown of miR-26a significantly improved cardiac insufficiency 
      caused by I/R, which also obviously increased both EF% and FS% in rats (p<0.05). 
      In addition, knockdown of miR-26a significantly inhibited myocardial infarction 
      caused by I/R injury, and reduced infarction area from (43.08+/-2.43) to 
      (21.54+/-1.82) (p<0.05). The results of H&E staining revealed that in I/R + miR-26a 
      siRNA group, myofilaments were arranged more orderly, the degree of degradation 
      and necrosis was significantly lower, and cellular edema was significantly 
      alleviated when compared with I/R group. Subsequent TUNEL staining demonstrated 
      that rats in I/R + miR-26a siRNA group showed a remarkably lower level of 
      myocardial apoptosis than I/R group (p<0.05). Meanwhile, the protein expression 
      levels of Bax and C-caspase3 were remarkably declined in I/R + miR-26a siRNA 
      group (p<0.05). Furthermore, the results of Western blotting showed that miR-26a 
      siRNA could significantly reverse the inhibition of GSK-3beta/beta-catenin signaling 
      pathway induced by I/R injury (p<0.05). CONCLUSIONS: Knockdown of miR-26a could 
      significantly improve I/R-induced myocardial injury and promote cardiac function 
      in rats. The possible underlying mechanism might be related to targeted 
      regulation of miR-26a on GSK-3beta/beta-catenin signaling pathway. Therefore, miR-26a 
      was expected to be a new therapeutic target for myocardial I/R injury.
FAU - Gong, D-D
AU  - Gong DD
AD  - Department of Cardiology, Dalian Municipal Central Hospital, Dalian, China. 
      jxddoc@163.com.
FAU - Yu, J
AU  - Yu J
FAU - Yu, J-C
AU  - Yu JC
FAU - Jiang, X-D
AU  - Jiang XD
LA  - eng
PT  - Journal Article
PL  - Italy
TA  - Eur Rev Med Pharmacol Sci
JT  - European review for medical and pharmacological sciences
JID - 9717360
RN  - 0 (MIRN26 microRNA, rat)
RN  - 0 (MicroRNAs)
RN  - 0 (beta Catenin)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Disease Models, Animal
MH  - Echocardiography
MH  - Glycogen Synthase Kinase 3 beta/*metabolism
MH  - Male
MH  - MicroRNAs/genetics/*metabolism
MH  - Myocardial Reperfusion Injury/diagnostic imaging/*metabolism
MH  - Myocardium/*metabolism/pathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction
MH  - beta Catenin/*metabolism
EDAT- 2019/09/06 06:00
MHDA- 2020/12/15 06:00
CRDT- 2019/09/06 06:00
PHST- 2019/09/06 06:00 [entrez]
PHST- 2019/09/06 06:00 [pubmed]
PHST- 2020/12/15 06:00 [medline]
AID - 18751 [pii]
AID - 10.26355/eurrev_201908_18751 [doi]
PST - ppublish
SO  - Eur Rev Med Pharmacol Sci. 2019 Aug;23(16):7073-7082. doi: 
      10.26355/eurrev_201908_18751.