Role and mechanism of miR-4472 targeting PIN1 in regulating the NF-κB/STAT3 signaling pathway in a rat model of hypoxic-ischemic encephalopathy
10.3760/cma.j.cn341190-20240117-00068
- VernacularTitle:miR-4472靶向PIN1调控NF-κB/STAT3信号通路在缺氧缺血性脑病大鼠模型中的作用及机制研究
- Author:
Yufeng ZHANG
1
;
Wen ZHU
;
Jue LIU
;
Qinlai YING
;
Weijie YU
Author Information
1. 嘉兴市第二医院儿科，嘉兴 314000
- Keywords:
Hypoxia-ischemia, brain;
MicroRNAs;
Proline;
Isomerases;
NF-kappa B;
Activating transcription factor 3
- From:
Chinese Journal of Primary Medicine and Pharmacy
2024;31(10):1473-1478
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the role and mechanism of microRNA (miR)-4472 targeting PIN1 in regulating the nuclear factor kappa B (NF-κB)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in a rat model of hypoxic-ischemic encephalopathy (HIE).Methods:Between January 2022 and January 2024, sixty Sprague-Dawley rats were randomly assigned to six groups at The Second Hospital of Jiaxing using a random number table method: a normal control group, an HIE model group, an inhibition control group, a miR-4472 inhibition group, a miR-4472 inhibition + interference control group, and a miR-4472 inhibition + PIN1 interference group, with ten rats in each group. There was no significant difference in body mass among the six groups (all P > 0.05). Rat models of HIE were established using the Rice-Vannucci method. Behavioral performance was assessed using the Morris water maze test, while neurological function was evaluated using the Longa scoring method. Apoptosis was detected using the TUNEL assay, and the expression of NF-κB and STAT3 protein was measured using Western blot analysis. Results:Compared with the HIE model group, the miR-4472 inhibition group and the miR-4472 inhibition + interference control group showed a shortened escape latency, while the miR-4472 inhibition + PIN1 interference group exhibited an extended escape latency (all P < 0.05). The number of platform crossings in the miR-4472 inhibition + PIN1 interference group [(2.13 ± 0.54) times] was significantly lower than that in the HIE model group [(3.56 ± 0.71) times], the inhibition control group [(3.61 ± 0.87) times], the miR-4472 inhibition group [(5.47 ± 1.29) times], and the miR-4472 inhibition + interference control group [(5.58 ± 1.32) times] ( t = 5.07, 4.57, 7.55, 7.65, all P < 0.05). The Longa score in the miR-4472 inhibition + PIN1 interference group [(3.03 ± 0.30) points] was significantly lower than that in the HIE model group [(2.45 ± 0.54) points], the inhibition control group [(2.38 ± 0.69) points], the miR-4472 inhibition group [(1.27 ± 0.46) points], and the miR-4472 inhibition + interference control group [(1.29 ± 0.51) points] ( t = 2.97, 2.73, 10.13, 9.30, all P < 0.05). The apoptosis rate of hippocampal neurons in the miR-4472 inhibition + PIN1 interference group [(25.34 ± 6.16)%] was significantly lower than that in the HIE model group [(18.42 ± 5.46)%], the inhibition control group [(17.95 ± 4.38)%], the miR-4472 inhibition group [(8.89 ± 2.10)%], and the miR-4472 inhibition + interference control group [(9.13 ± 2.57)%] ( t = 2.97, 2.73, 10.13, 9.30, all P < 0.05). Compared with the HIE model group, the miR-4472 inhibition group and the miR-4472 inhibition + interference control group exhibited decreased gray values of NF-κB and STAT3 protein, while the miR-4472 inhibition + PIN1 interference group showed increased gray values of NF-κB and STAT3 protein (all P < 0.05). Conclusion:miR-4472 targets and regulates PIN1, which contributes to HIE injury through the activation of the NF-κB/STAT3 signaling pathway.
