Biomaterial Database

FOXC2 Alleviates Myocardial Ischemia-Reperfusion Injury in Rats through Regulating Nrf2/HO-1 Signaling Pathway. 2021

Rui Wang, and Yonggang Wu, and Shoutao Jiang

Department of Cardiology, Guangzhou Hospital of Integrated Chinese and Western Medicine, Guangzhou, China.

OBJECTIVE Myocardial ischemia-reperfusion injury (MIRI) is the leading cause of death in patients with cardiovascular disease. The purpose of this study is to investigate the effect and mechanism of forkhead box C2 (FOXC2) on MIRI in rats. METHODS We made ischemia-reperfusion (I/R) models for rats by performing I/R surgery. After 3 hours, 3 days, and 7 days of reperfusion, we detected the structure and function of rat myocardium by 2, 3, 5-triphenyl tetrazolium chloride staining, echocardiography, lactate dehydrogenase kit, and haematoxylin-eosin staining. The change of FOXC2 expression in myocardial tissue was also detected. Then, we increased the expression of FOXC2 in rats by adenovirus transfection to clarify the effect of FOXC2 on changes of oxidative stress and inflammation of rat myocardium. In addition, we detected the effect of FOXC2 overexpression plasmid on the function of H9c2 cells in vitro. The expression changes of Nrf2/HO-1 in myocardial cells were also detected to clarify the mechanism of action of FOXC2. RESULTS The expression of FOXC2 in I/R rats was significantly lower than that in the sham group. After overexpressing FOXC2 in I/R rats, we found that the expression of SOD1/2 of rat myocardium and inflammatory factors in the serum were significantly reduced. Overexpression of FOXC2 also increased the viability and antioxidant capacity of H9c2 cells. In addition, FOXC2 was found to increase the activity of the Nrf2/HO-1 signaling pathway in myocardial cells, and the inhibition of Nrf2/HO-1 signaling pathway attenuated the protective effect of FOXC2 on myocardial cells. CONCLUSIONS MIRI in rats was accompanied by low expression of FOXC2 in myocardial tissue. Overexpression of FOXC2 reduces the level of inflammation and oxidative stress in myocardial tissue by promoting the Nrf2/HO-1 signaling pathway, thereby alleviating MIRI.

UI	MeSH Term	Description	Entries
D007249	Inflammation	A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.	Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D008297	Male		Males
D005786	Gene Expression Regulation	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.	Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006419	Heme Oxygenase (Decyclizing)	A mixed function oxidase enzyme which during hemoglobin catabolism catalyzes the degradation of heme to ferrous iron, carbon monoxide and biliverdin in the presence of molecular oxygen and reduced NADPH. The enzyme is induced by metals, particularly cobalt.	Haem Oxygenase,Heme Oxygenase,Oxygenase, Haem,Oxygenase, Heme
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000975	Antioxidants	Naturally occurring or synthetic substances that inhibit or retard oxidation reactions. They counteract the damaging effects of oxidation in animal tissues.	Anti-Oxidant,Antioxidant,Antioxidant Activity,Endogenous Antioxidant,Endogenous Antioxidants,Anti-Oxidant Effect,Anti-Oxidant Effects,Anti-Oxidants,Antioxidant Effect,Antioxidant Effects,Activity, Antioxidant,Anti Oxidant,Anti Oxidant Effect,Anti Oxidant Effects,Anti Oxidants,Antioxidant, Endogenous,Antioxidants, Endogenous
D015398	Signal Transduction	The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.	Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D015428	Myocardial Reperfusion Injury	Damage to the MYOCARDIUM resulting from MYOCARDIAL REPERFUSION (restoration of blood flow to ischemic areas of the HEART.) Reperfusion takes place when there is spontaneous thrombolysis, THROMBOLYTIC THERAPY, collateral flow from other coronary vascular beds, or reversal of vasospasm.	Reperfusion Injury, Myocardial,Injury, Myocardial Reperfusion,Myocardial Ischemic Reperfusion Injury,Injuries, Myocardial Reperfusion,Myocardial Reperfusion Injuries,Reperfusion Injuries, Myocardial
D017207	Rats, Sprague-Dawley	A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.	Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D051267	NF-E2-Related Factor 2	A basic-leucine zipper transcription factor that was originally described as a transcriptional regulator controlling expression of the BETA-GLOBIN gene. It may regulate the expression of a wide variety of genes that play a role in protecting cells from oxidative damage.	Nfe2l2 Protein,Nuclear Factor (Erythroid-Derived 2)-Like 2 Protein,Nuclear Factor E2-Related Factor 2,NF E2 Related Factor 2,Nuclear Factor E2 Related Factor 2