PMID- 32894933 OWN - NLM STAT- MEDLINE DCOM- 20201105 LR - 20201105 IS - 0393-974X (Print) IS - 0393-974X (Linking) VI - 34 IP - 4 DP - 2020 Jul-Aug TI - MiR-424 Inhibits neuronal apoptosis in rats with cerebral infarction through regulating TGF-beta1/Smad3 signaling pathway. PG - 1285-1296 LID - 10.23812/20-176-A [doi] AB - It has been reported that micro ribonucleic acid (miR)-424 is an important molecule in cerebral ischemia. However, the precise mechanism of action and biological effects of miR-424 remain to be further explored. miR-424 mimic and miR-424 inhibitor were injected via the caudal vein in rats, and the effect of miR-424 expression on brain tissue damage induced by middle cerebral artery occlusion (MCAO) was detected. The miR-424 mimic-induced changes in genomic levels were detected via the gene chip assay, and the signaling pathways regulated by miR-424 and its potential targets were explored combined with target prediction. Then the effect of miR-424 mimic on apoptosis of PC12 cells induced by oxygen-glucose deprivation (OGD) was determined using Annexin V/PI assay. Finally, drosophila mothers against decapentaplegic protein 7 (Smad7) was overexpressed to further verify the mechanism of action of miR-424 mimic. Compared with that in the sham group, the expression of miR-424 in brain tissues significantly declined in the model group. The results of 2,3,5-triphenyltetrazolium chloride (TTC) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay revealed that the miR-424 mimic obviously reduced the cerebral infarction area and apoptosis level of brain tissues, while the miR-424 inhibitor obviously increased the cerebral infarction area and apoptosis level of brain tissues. It was found, using bioinformatics and KEGG enrichment analysis, that differentially expressed genes induced by miR-424 were significantly enriched in the transforming growth factor-beta (TGF-beta) signaling pathway. According to the results of reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting, the miR-424 mimic could evidently lower the expression of Smad7, thus activating the TGF-beta1/Smad3 signaling pathway. Overexpression of Smad7 could weaken the protective effect of miR-424 mimic on ischemic-hypoxic cells. Increasing the expression of miR-424 can inhibit Smad7 to activate the TGF-beta1/Smad3 signaling pathway, thereby exerting a protective effect against the brain tissue damage induced by MCAO. CI - Copyright 2020 Biolife Sas. www.biolifesas.org. FAU - Gui, S H AU - Gui SH AD - Department of Neurology, Affiliated Hospital of Jiangnan University/The Third People's Hospital of Wuxi, Wuxi, China. FAU - Wang, Y M AU - Wang YM AD - Department of Neurology, Affiliated Hospital of Jiangnan University/The Third People's Hospital of Wuxi, Wuxi, China. FAU - Fan, C Y AU - Fan CY AD - Department of Neurology, Affiliated Hospital of Jiangnan University/The Third People's Hospital of Wuxi, Wuxi, China. FAU - Han, L K AU - Han LK AD - Department of Neurology, Affiliated Hospital of Jiangnan University/The Third People's Hospital of Wuxi, Wuxi, China. FAU - Wang, T G AU - Wang TG AD - Department of Neurology, Affiliated Hospital of Jiangnan University/The Third People's Hospital of Wuxi, Wuxi, China. FAU - Di, M Q AU - Di MQ AD - Department of Neurology, Affiliated Hospital of Jiangnan University/The Third People's Hospital of Wuxi, Wuxi, China. FAU - Gu, J Q AU - Gu JQ AD - Department of Neurology, Affiliated Hospital of Jiangnan University/The Third People's Hospital of Wuxi, Wuxi, China. LA - eng PT - Journal Article PL - Italy TA - J Biol Regul Homeost Agents JT - Journal of biological regulators and homeostatic agents JID - 8809253 RN - 0 (MicroRNAs) RN - 0 (Smad3 Protein) RN - 0 (Smad3 protein, rat) RN - 0 (Transforming Growth Factor beta1) SB - IM MH - Animals MH - Apoptosis MH - MicroRNAs/genetics MH - Neurons MH - Rats MH - Rats, Sprague-Dawley MH - *Signal Transduction MH - Smad3 Protein MH - Transforming Growth Factor beta1/genetics OTO - NOTNLM OT - TGF-beta1/Smad3 signaling pathway OT - apoptosis OT - cerebral infarction OT - miR-424 OT - neurons EDAT- 2020/09/09 06:00 MHDA- 2020/11/06 06:00 CRDT- 2020/09/08 04:19 PHST- 2020/09/08 04:19 [entrez] PHST- 2020/09/09 06:00 [pubmed] PHST- 2020/11/06 06:00 [medline] AID - 36 [pii] AID - 10.23812/20-176-A [doi] PST - ppublish SO - J Biol Regul Homeost Agents. 2020 Jul-Aug;34(4):1285-1296. doi: 10.23812/20-176-A.