Fibroblast growth factor 5 overexpression ameliorated lipopolysaccharide-induced apoptosis of hepatocytes through regulation of the phosphoinositide-3-kinase/protein kinase B pathway. 2022

Shengyu Cui, and Yuhua Li, and Xutao Zhang, and Bing Wu, and Ming Li, and Jixian Gao, and Lin Xu, and Hao Xia
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.

BACKGROUND Sepsis is a systemic inflammatory syndrome induced by several infectious agents. Multiple organs are affected by sepsis, including the liver, which plays an important role in metabolism and immune homeostasis. Fibroblast growth factors (FGFs) participate in several biological processes, although the role of FGF5 in sepsis is unclear. METHODS In this study, lipopolysaccharide (LPS) was administrated to mice to establish a sepsis-induced liver injury. A similar in vitro study was conducted using L-02 hepatocytes. Western blot and immunohistochemistry staining were performed to evaluate the FGF5 expression level in liver tissues and cells. Inflammatory cell infiltrations, cleaved-caspase-3 expressions, reactive oxygen species and levels of inflammatory cytokines were detected by immunofluorescence, dihydroethidium staining, and reverse transcription quantitative polymerase chain reaction analysis, respectively. Flow cytometry was used to detect the apoptosis level of cells. In addition, ribonucleic acid (RNA)-sequencing was applied to explore the possible mechanism by which FGF5 exerted effects. RESULTS LPS administration caused FGF5 down-regulation in the mouse liver as well as in L-02 hepatocytes. Additionally, with FGF5 overexpression, liver injury and the level of hepatocyte apoptosis were ameliorated. Further, RNA sequencing performed in hepatocytes revealed the phosphoinositide-3-kinase/protein kinase B (PI3K/AKT) pathway as a possible pathway regulated by FGF5 . This was supported using an inhibitor of the PI3K/AKT pathway, which abrogated the protective effect of FGF5 in LPS-induced hepatocyte injury. CONCLUSIONS The anti-apoptotic effect of FGF5 on hepatocytes suffering from LPS has been demonstrated and was dependent on the activation of the PI3K/AKT signaling pathway.

UI MeSH Term Description Entries
D008070 Lipopolysaccharides Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed) Lipopolysaccharide,Lipoglycans
D010716 Phosphatidylinositols Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to the hexahydroxy alcohol, myo-inositol. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid, myo-inositol, and 2 moles of fatty acids. Inositide Phospholipid,Inositol Phosphoglyceride,Inositol Phosphoglycerides,Inositol Phospholipid,Phosphoinositide,Phosphoinositides,PtdIns,Inositide Phospholipids,Inositol Phospholipids,Phosphatidyl Inositol,Phosphatidylinositol,Inositol, Phosphatidyl,Phosphoglyceride, Inositol,Phosphoglycerides, Inositol,Phospholipid, Inositide,Phospholipid, Inositol,Phospholipids, Inositide,Phospholipids, Inositol
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
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D051057 Proto-Oncogene Proteins c-akt Protein-serine-threonine kinases that contain PLECKSTRIN HOMOLOGY DOMAINS and are activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. They play a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells. akt Proto-Oncogene Protein,c-akt Protein,AKT1 Protein Kinase,AKT2 Protein Kinase,AKT3 Protein Kinase,Akt-alpha Protein,Akt-beta Protein,Akt-gamma Protein,Protein Kinase B,Protein Kinase B alpha,Protein Kinase B beta,Protein Kinase B gamma,Protein-Serine-Threonine Kinase (Rac),Proto-Oncogene Protein Akt,Proto-Oncogene Protein RAC,Proto-Oncogene Proteins c-akt1,Proto-Oncogene Proteins c-akt2,Proto-Oncogene Proteins c-akt3,RAC-PK Protein,Rac Protein Kinase,Rac-PK alpha Protein,Rac-PK beta Protein,Related to A and C-Protein,c-akt Proto-Oncogene Protein,Akt alpha Protein,Akt beta Protein,Akt gamma Protein,Akt, Proto-Oncogene Protein,Protein, akt Proto-Oncogene,Protein, c-akt Proto-Oncogene,Proteins c-akt1, Proto-Oncogene,Proteins c-akt2, Proto-Oncogene,Proteins c-akt3, Proto-Oncogene,Proto Oncogene Protein Akt,Proto Oncogene Protein RAC,Proto Oncogene Proteins c akt,Proto Oncogene Proteins c akt1,Proto Oncogene Proteins c akt2,Proto Oncogene Proteins c akt3,Proto-Oncogene Protein, akt,Proto-Oncogene Protein, c-akt,RAC PK Protein,RAC, Proto-Oncogene Protein,Rac PK alpha Protein,Rac PK beta Protein,Related to A and C Protein,akt Proto Oncogene Protein,alpha Protein, Rac-PK,c akt Proto Oncogene Protein,c-akt, Proto-Oncogene Proteins,c-akt1, Proto-Oncogene Proteins,c-akt2, Proto-Oncogene Proteins,c-akt3, Proto-Oncogene Proteins
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D051521 Fibroblast Growth Factor 5 A fibroblast growth factor that may play a role in regulation of HAIR FOLLICLE phenotype. Spontaneous mutation of the gene for this protein results in a strain of MICE with abnormally long hair, referred to as angora mice.
D018805 Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by HYPOTENSION despite adequate fluid infusion, it is called SEPTIC SHOCK. Bloodstream Infection,Pyaemia,Pyemia,Pyohemia,Blood Poisoning,Poisoning, Blood,Septicemia,Severe Sepsis,Blood Poisonings,Bloodstream Infections,Infection, Bloodstream,Poisonings, Blood,Pyaemias,Pyemias,Pyohemias,Sepsis, Severe,Septicemias
D019869 Phosphatidylinositol 3-Kinases Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell. PI-3 Kinase,Phosphatidylinositol-3-OH Kinase,PtdIns 3-Kinase,PI 3-Kinase,PI-3K,PI3 Kinases,PI3-Kinase,Phosphoinositide 3 Kinases,Phosphoinositide 3-Hydroxykinase,PtdIns 3-Kinases,3-Hydroxykinase, Phosphoinositide,Kinase, PI-3,Kinase, Phosphatidylinositol-3-OH,Kinases, PI3,Kinases, Phosphoinositide 3,PI 3 Kinase,PI3 Kinase,Phosphatidylinositol 3 Kinases,Phosphatidylinositol 3 OH Kinase,Phosphoinositide 3 Hydroxykinase,PtdIns 3 Kinase,PtdIns 3 Kinases
D022781 Hepatocytes The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules. Hepatic Cells,Cell, Hepatic,Cells, Hepatic,Hepatic Cell,Hepatocyte

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