PMID- 34919217
OWN - NLM
STAT- MEDLINE
DCOM- 20220322
LR  - 20220322
IS  - 2284-0729 (Electronic)
IS  - 1128-3602 (Linking)
VI  - 25
IP  - 23
DP  - 2021 Dec
TI  - A study on the mechanism of PP2A in the recovery of SCI in rats through 
      downregulation of MMP-9 via MAPK signaling pathway.
PG  - 7195-7203
LID - 27411 [pii]
LID - 10.26355/eurrev_202112_27411 [doi]
AB  - OBJECTIVE: The aim of this study was to investigate the mechanism of action of 
      protein phosphatase 2A (PP2A) in the recovery of spinal cord injury (SCI) in rats 
      by downregulating matrix metalloproteinase 9 (MMP-9) via the mitogen-activated 
      protein kinase (MAPK) signaling pathway. MATERIALS AND METHODS: A model of SCI 
      was first successfully established in rats. A total of three groups were set, 
      including: sham operation group (A group), SCI group (B group) and PP2A group (C 
      group). The Basso, Beattie and Bresnahan (BBB) motor function score and inclined 
      plane test were adopted to evaluate the motor ability and limb muscle strength of 
      rats in each group. The water content in spinal cord tissues was detected as 
      well. Quantitative Polymerase Chain Reaction (qPCR) assay was performed to 
      analyze the messenger ribonucleic acid (mRNA) expression levels of MAPK, MMP-2, 
      and MMP-9 in spinal cord tissues. The expressions of inflammatory factors tumor 
      necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and IL-6 in each group of rats 
      were determined via enzyme-linked immunosorbent assay (ELISA). Western blotting 
      (WB) was employed to measure the protein expression levels of MAPK, MMP-2 and 
      MMP-9 in each group of rats. Additionally, the apoptosis of nerve cells in spinal 
      cord tissues was analyzed through terminal deoxynucleotidyl transferase-mediated 
      dUTP nick end labeling (TUNEL) assay. RESULTS: The BBB score was 8.8 points in C 
      group at 5 d after operation, which was significantly different from that in B 
      group (p<0.05). The slope in B and C groups was clearly lower than that in A 
      group at each time point (p<0.001). Meanwhile, it was significantly higher in C 
      group than that in B group at 5, 7 and 9 d (p<0.05). The edema rate rose notably 
      in B group compared with A group (p<0.001). However, spinal cord edema was 
      remarkably relieved after treatment with FRY720 (p<0.01), suggesting that PP2A 
      agonist could treat SCI in rats. The levels of cytokines TNF-alpha, IL-1beta and IL-6 
      were markedly higher in B group than those in A group (p<0.01). However, they 
      were significantly reduced after treatment with PP2A agonist (p<0.01). In 
      comparison with A group, B group exhibited remarkably decreased mRNA expression 
      of MAPK and elevated mRNA expressions of MMP-2 and MMP-9 (p<0.01). However, C 
      group exhibited an upregulated mRNA expression of MAPK (p<0.05), a downregulated 
      mRNA expression of MMP-9 (p<0.01), and an undifferentiated mRNA expression of 
      MMP-2 (p>0.05). Compared with B group, the protein expression level of MAPK 
      significantly increased (p<0.05), while that of MMP-9 evidently decreased in C 
      group (p<0.05). Besides, no statistically significant difference was observed in 
      the protein expression level of MMP-2 between C group and B group (p>0.05). 
      Compared with that in A group, the apoptosis rate significantly increased in B 
      group (p<0.001). In addition, the apoptosis rate was significantly lower in C 
      group than that in B group, showing a statistically significant difference 
      (p<0.01). CONCLUSIONS: PP2A downregulates MMP-9 through the MAPK signaling 
      pathway, thereby conducing to the recovery of SCI in rats.
FAU - Luo, L
AU  - Luo L
AD  - Department of Orthopaedic Hand Surgery, The Affiliated Hospital of Traditional 
      Chinese Medicine of Southwest Medical University, Luzhou, China. 
      hjmdoc1980@163.com.
FAU - Yang, J-X
AU  - Yang JX
FAU - Luo, T
AU  - Luo T
FAU - Liu, D
AU  - Liu D
FAU - Wu, G-H
AU  - Wu GH
FAU - He, J-M
AU  - He JM
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 (RNA, Messenger)
RN  - EC 3.1.3.16 (Protein Phosphatase 2)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.24 (Mmp2 protein, rat)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - EC 3.4.24.35 (Mmp9 protein, rat)
SB  - IM
MH  - Animals
MH  - Apoptosis/genetics
MH  - Disease Models, Animal
MH  - Down-Regulation
MH  - Inflammation/genetics/physiopathology
MH  - MAP Kinase Signaling System/*genetics
MH  - Male
MH  - Matrix Metalloproteinase 2/genetics
MH  - Matrix Metalloproteinase 9/*genetics
MH  - Muscle Strength/physiology
MH  - Protein Phosphatase 2/*metabolism
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Spinal Cord Injuries/genetics/*physiopathology
EDAT- 2021/12/18 06:00
MHDA- 2022/03/23 06:00
CRDT- 2021/12/17 12:25
PHST- 2021/12/17 12:25 [entrez]
PHST- 2021/12/18 06:00 [pubmed]
PHST- 2022/03/23 06:00 [medline]
AID - 27411 [pii]
AID - 10.26355/eurrev_202112_27411 [doi]
PST - ppublish
SO  - Eur Rev Med Pharmacol Sci. 2021 Dec;25(23):7195-7203. doi: 
      10.26355/eurrev_202112_27411.