Inhibition of SphK1/S1P Signaling Pathway Alleviates Fibrosis and Inflammation of Rat Myocardium after Myocardial Infarction. 2022

Xiaokui Wu, and Junwei Xu, and Xiangyu Li, and Jian Dai, and Linlin Wang
Department of Cardiology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing Chest Hospital, Nanjing, China.

The sphingosine kinase 1 (SphK1)/sphingosine-1-phosphate (S1P) signaling pathway is involved in fibrosis and inflammatory responses of myocardial tissue after myocardial infarction (MI). The purpose of our study was to explore the role of SphK1/S1P signaling pathway in myocardial injury after MI. We used Sprague-Dawley (SD) rats to make MI models and detected the changes of SphK1 and S1P in rats at 1, 7, and 14 days after MI. SphK1 inhibitor PF543 was used to treat MI rats, and we detected the changes in myocardial function and structure in rats by cardiac function test, 2,3,5-triphenyl tetrazolium staining, and histological staining. In addition, we used H2O2 to induce H9c2 cell injury to investigate the effect of PF543 on the viability of myocardial cells. Myocardial tissue lesions and fibrosis were observed at 7 and 14 days after MI, and the expressions of SphK1 and S1P in the injured myocardial tissues increased significantly in day 7 and day 14 in comparison to the control group. After treatment of MI rats with PF543, the structure of rat myocardial tissue was significantly improved and the degree of fibrosis was reduced. After MI, the expression of α-SMA and collagen I in the myocardium of rats was significantly increased while PF543 decreased their expression. PF543 also improved the cardiac function of MI rats and reduced the expression of IL-1β, IL-6, and TNF-α in the serum. PF543 also increased the viability of H9c2 cells in vitro. The inhibition of the SphK1/S1P signaling pathway contributed to the relief of myocardial injury in MI rats. PF543 improved the myocardial structure and function of MI rats and reduced the level of fibrosis and inflammation in MI rats.

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
D008246 Lysophospholipids Derivatives of PHOSPHATIDIC ACIDS that lack one of its fatty acyl chains due to its hydrolytic removal. Lysophosphatidic Acids,Lysophospholipid,Acids, Lysophosphatidic
D009203 Myocardial Infarction NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION). Cardiovascular Stroke,Heart Attack,Myocardial Infarct,Cardiovascular Strokes,Heart Attacks,Infarct, Myocardial,Infarction, Myocardial,Infarctions, Myocardial,Infarcts, Myocardial,Myocardial Infarctions,Myocardial Infarcts,Stroke, Cardiovascular,Strokes, Cardiovascular
D009206 Myocardium The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow. Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D005355 Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Cirrhosis,Fibroses
D006861 Hydrogen Peroxide A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. Hydrogen Peroxide (H2O2),Hydroperoxide,Oxydol,Perhydrol,Superoxol,Peroxide, Hydrogen
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
D013110 Sphingosine An amino alcohol with a long unsaturated hydrocarbon chain. Sphingosine and its derivative sphinganine are the major bases of the sphingolipids in mammals. (Dorland, 28th ed) 4-Sphingenine,4 Sphingenine
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
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

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