PMID- 31081106
OWN - NLM
STAT- MEDLINE
DCOM- 20200909
LR  - 20200909
IS  - 2284-0729 (Electronic)
IS  - 1128-3602 (Linking)
VI  - 23
IP  - 8
DP  - 2019 Apr
TI  - MiR-34a affects hepatocyte proliferation during hepatocyte regeneration through 
      regulating Notch/HIF-1alpha signaling pathway.
PG  - 3503-3511
LID - 17716 [pii]
LID - 10.26355/eurrev_201904_17716 [doi]
AB  - OBJECTIVE: To explore the influences of micro ribonucleic acid (miR)-34a on liver 
      function and hepatocyte proliferation during hepatocyte regeneration in rats and 
      its mechanism. MATERIALS AND METHODS: A total of 80 Sprague-Dawley rats were 
      randomly divided into 4 groups: Sham-2 d group (2 days after hepatectomy), 
      Sham-10 d group (10 days after hepatectomy), miR-34a siRNA-2d group (miR-34a 
      knockdown + 2 days after hepatectomy) and miR-34a siRNA-10 d group (miR-34a 
      knockdown + 10 days after hepatectomy), with 20 rats in each group. Serum levels 
      of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate 
      dehydrogenase (LDH) were detected at 2 d and 10 d after the operation. The rat 
      liver was harvested for calculating the liver/body weight ratio. In addition, the 
      deoxyribonucleic acid (DNA) content in rat hepatocytes was detected via Feulgen 
      staining. The pathological changes in rat liver were detected via 
      hematoxylin-eosin (H&E) staining. Moreover, the hepatocyte apoptosis in each 
      group was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick 
      end labeling (TUNEL) staining. Expression levels of proliferating cell nuclear 
      antigen (PCNA), Notch1 intracellular domain (NICD), and hypoxia-inducible 
      factor-1alpha (HIF-1alpha) in liver tissues of each group were detected via 
      immunohistochemistry and Western blotting. RESULTS: No significant differences in 
      the liver/body weight ratio, serum levels of ALT, AST, LDH, pathological 
      structure of the liver, hepatocyte apoptosis level, and PCNA expression in 
      hepatocytes were found between miR-34a siRNA-2 d group and Sham-2 d group. 
      However, the expression levels of NICD and HIF-1alpha in the liver significantly 
      increased in miR-34a siRNA-2 d group compared with those in Sham-2 d group 
      (p<0.05). On the contrary, compared with those in Sham-10 d group, the liver 
      function and hepatocyte regeneration level significantly increased in miR-34a 
      siRNA-10 d group. Increased liver/body weight ratio, remarkable decline in serum 
      levels of ALT, AST, and LDH, significant alleviation of pathological injury of 
      liver tissues, decreased the apoptosis level and upregulated PCNA protein were 
      observed in miR-34a siRNA-10 d group than those of Sham-10 d group. The 
      Notch/HIF-1alpha signaling pathway was also significantly activated. CONCLUSIONS: 
      MiR-34a knockdown can significantly enhance the liver function and hepatocyte 
      regeneration ability in rats at 10 d after hepatectomy through activating the 
      Notch/HIF-1alpha signaling pathway.
FAU - Mai, E-H
AU  - Mai EH
AD  - Department of Hepatobiliary Surgery, Luoyang Central Hospital, Luoyang, China. 
      maierhui6912457@126.com.
FAU - Lei, T
AU  - Lei T
FAU - Li, S-Q
AU  - Li SQ
FAU - Hu, P-G
AU  - Hu PG
FAU - Xu, T
AU  - Xu T
FAU - Jia, F-X
AU  - Jia FX
FAU - Zha, Z-M
AU  - Zha ZM
FAU - Zhang, S-J
AU  - Zhang SJ
FAU - Ding, F-H
AU  - Ding FH
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 (Hif1a protein, rat)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (MIRN34 microRNA, rat)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Notch)
SB  - IM
MH  - Animals
MH  - Cell Proliferation/genetics
MH  - Disease Models, Animal
MH  - Gene Knockdown Techniques
MH  - Hepatectomy/*adverse effects
MH  - Hepatocytes/*physiology
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
MH  - Liver/cytology/physiology/surgery
MH  - Liver Function Tests
MH  - Liver Neoplasms/surgery
MH  - Liver Regeneration/*genetics
MH  - MicroRNAs/genetics/*metabolism
MH  - RNA, Small Interfering/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Notch/metabolism
MH  - Signal Transduction/*genetics
EDAT- 2019/05/14 06:00
MHDA- 2020/09/10 06:00
CRDT- 2019/05/14 06:00
PHST- 2019/05/14 06:00 [entrez]
PHST- 2019/05/14 06:00 [pubmed]
PHST- 2020/09/10 06:00 [medline]
AID - 17716 [pii]
AID - 10.26355/eurrev_201904_17716 [doi]
PST - ppublish
SO  - Eur Rev Med Pharmacol Sci. 2019 Apr;23(8):3503-3511. doi: 
      10.26355/eurrev_201904_17716.