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1.
Gen Comp Endocrinol ; 351: 114480, 2024 05 15.
Article in English | MEDLINE | ID: mdl-38401858

ABSTRACT

Neuropeptide Y is known to be directly or indirectly involved in immune regulation. The immune effects of NPY include immune cell transport, helper T cell differentiation, cytokine secretion, staining and killer cell activity, phagocytosis and production of reactive oxygen species. In this study, we investigated the immunoprotective effect of synthetic NPY on largemouth bass larvae. For the first time, the dose and time effects of NPY injection on largemouth bass was explored, and then Poly I:C and LPS infection was carried out in juvenile largemouth bass, respectively, after the injection of NPY. The results showed that NPY could reduce the inflammatory response by inhibiting the expression of il-1ß, tgf-ß, ifn-γ and other immune factors in head kidney, spleen and brain, and alleviate the immune stress caused by strong inflammatory response in the early stage of infection. Meanwhile, NPY injection ameliorated the intestinal tissue damage caused by infection. This study provides a new way to protect juvenile fish and improve its innate immunity.


Subject(s)
Bass , Animals , Bass/genetics , Neuropeptide Y/pharmacology , Neuropeptide Y/metabolism , Immunity, Innate , Gene Expression
2.
Neuroendocrinology ; 114(4): 365-385, 2024.
Article in English | MEDLINE | ID: mdl-38142691

ABSTRACT

INTRODUCTION: The perception of hunger is a complex physiological process that requires precise coordination between the central and peripheral tissues. METHODS: In this study, tilapia fasted for 24 h was chosen to establish a hunger model to study the mechanism of homeostasis recovery under the joint regulation of the central nervous system (CNS) and peripheral tissues. RESULTS: The gastric and intestinal contents of tilapia were predominantly depleted after a fasting period of 9 h and 24 h, respectively. The serum glucose level significantly decreased at the 9-h and 24-h fasting, respectively, and the glucokinase-dependent glucosensing mechanism in the liver was identified as well as the significant activation of phospho-AMPK. However, fasting for 24 h did not activate glucosensing mechanisms and AMPK signaling pathways in the hypothalamus. On the other hand, significant reductions were observed in the mRNA levels of the lipid synthesis-related genes fas and accα, and the serum triglyceride levels as well. The mRNA levels of npy, agrp, pomc, and cart in the hypothalamus fluctuated during the fasting period without significant differences. With in situ hybridization npy signals upregulated in the ventral zone of posterior periventricular nucleus after 24-h fasting, pomc signals enhanced in the lateral tuberal nucleus. Based on the serum metabolomic analysis, the levels of branched-chain amino acids, butyrate, and short-chain acylcarnitine decreased, while those of medium- and long-chain acylcarnitine increased. CONCLUSION: Fasting for 24 h resulted in changes in npy and pomc signals within the hypothalamus and triggered the glucosensing mechanism in the liver of tilapia. This study is beneficial for elucidating the response of neuropeptides in the CNS to the changes of nutritional factors when hungry.


Subject(s)
Carnitine/analogs & derivatives , Neuropeptide Y , Neuropeptides , Neuropeptide Y/metabolism , Hunger , Pro-Opiomelanocortin/metabolism , AMP-Activated Protein Kinases/metabolism , Neuropeptides/metabolism , Hypothalamus/metabolism , Fasting , Agouti-Related Protein/metabolism , RNA, Messenger/metabolism
3.
Fish Shellfish Immunol ; 141: 109072, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37709180

ABSTRACT

Neuropeptide Y (NPY), an important neurotransmitter, is widely distributed in the nervous systems of vertebrates. Multiple functions of NPY in mammals include the regulation of brain activity, emotion, stress response, feeding, digestion, metabolism and immune function. In the present study, we used synthetic NPY to immerse juvenile tilapia, thus firstly exploring the dose and time effect of this immersion. The results showed that the expression level of y8b and serum glucose increased after NPY immersion. When juvenile tilapia was challenged with Streptococcus agalactiae (S. agalactiae), no matter before or after the administration of NPY-immersion, it was found that NPY immersion could inhibit the expression of il-1ß induced by S. agalactiae in telencephalon, hypothalamus, spleen and head kidney, and then promote the expression of il-10. In addition, NPY-immersion could reduce the activity of serum SOD but increase that of lysozyme, and ameliorate tissue damage in the head kidney and spleen of juvenile tilapia caused by S. agalactiae infection. This study firstly proposes the potential of NPY to be an immune protect factor in juvenile fish, and the results can provide a reference for the application of immersion administration in the immune protection of juvenile fish.

4.
Front Endocrinol (Lausanne) ; 13: 1023842, 2022.
Article in English | MEDLINE | ID: mdl-36267563

ABSTRACT

Feeding and growth are two closely related and important physiological processes in living organisms. Studies in mammals have provided us with a series of characterizations of neuropeptides and their receptors as well as their roles in appetite control and growth. The central nervous system, especially the hypothalamus, plays an important role in the regulation of appetite. Based on their role in the regulation of feeding, neuropeptides can be classified as orexigenic peptide and anorexigenic peptide. To date, the regulation mechanism of neuropeptide on feeding and growth has been explored mainly from mammalian models, however, as a lower and diverse vertebrate, little is known in fish regarding the knowledge of regulatory roles of neuropeptides and their receptors. In recent years, the development of omics and gene editing technology has accelerated the speed and depth of research on neuropeptides and their receptors. These powerful techniques and tools allow a more precise and comprehensive perspective to explore the functional mechanisms of neuropeptides. This paper reviews the recent advance of omics and gene editing technologies in neuropeptides and receptors and their progresses in the regulation of feeding and growth of fish. The purpose of this review is to contribute to a comparative understanding of the functional mechanisms of neuropeptides in non-mammalians, especially fish.


Subject(s)
Neuropeptide Y , Neuropeptides , Animals , Neuropeptide Y/genetics , Eating/physiology , Gene Editing , Neuropeptides/genetics , Somatostatin , Fishes/genetics , Mammals/genetics
5.
Int Immunopharmacol ; 108: 108742, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35378447

ABSTRACT

BACKGROUND: Interleukin-33 (IL-33) is a member of the interleukin-1 family, which is reported to be important across a range of diseases. However, the mechanisms underlying IL-33/ST2 axis in infectious diseases have not yet been fully addressed. METHODS: We established both lipopolysaccharide (LPS)-induced injuryin T cells and Listeria monocytogenes (Lm) infection model to determine the effect of IL-33 on infectious immunity. RESULTS: The T cell proliferation was inhibited by LPS while IL-33 could reverse the outcome. Further, apoptosis was significantly promoted after serum stimulation (ST)2 knockdown, suggesting IL-33, acting through its receptor ST2, may attenuate the inhibitory effect of LPS on T cells through the apoptotic signaling pathway. In this study, we also identified an IL-33-mediated mechanism of T cell differentiation in pregnant mice infected with Lm. Here, we observed the elevated expression of IL-33 in pregnant mice infected with Lm. Furthermore, we revealed that blocking IL-33 markedly decreased the abortion rate and placental bacterial load, but weakened placental inflammatory repair, by inhibiting Th2 cell-mediated immune responses and relatively intensifying Th1-dominent immunoreaction. CONCLUSIONS: These findings reveal a previously unidentified mechanism underlying IL-33/ST2 axis. IL-33 signaling and targeting T cell-mediated immunity may present a new therapeutic strategy for the treatment of infectious diseases.


Subject(s)
Interleukin-1 Receptor-Like 1 Protein , Interleukin-33 , Listeria , Listeriosis , T-Lymphocytes , Animals , Female , Interleukin-1 Receptor-Like 1 Protein/genetics , Interleukin-33/genetics , Lipopolysaccharides , Listeriosis/immunology , Lymphocyte Activation , Mice , Placenta , Pregnancy , T-Lymphocytes/immunology
6.
Gen Comp Endocrinol ; 316: 113945, 2022 01 15.
Article in English | MEDLINE | ID: mdl-34826429

ABSTRACT

Stress is known as the process of biological responses evoked by internal or external stimuli. The ability to sense, integrate and respond to stress signals is a requisite for life. Temperature and photoperiod are very important environmental factors for animals. In addition, stress signals can also be inputted from peripheral tissue, such as starvation and inflammation. Through afferent pathways, stress signals input to the central nervous system (CNS), where various signals will integrate, and the integrated information will transmit to the peripheral effectors. As the regulators of neural activity, neuropeptides play important roles in these processes. The present review summarizes recent findings about the integration mechanism of stress signals in the CNS, emphasizing on the role of neuropeptides.


Subject(s)
Neuropeptides , Animals , Central Nervous System/metabolism , Neuropeptides/metabolism , Temperature
7.
Peptides ; 138: 170505, 2021 04.
Article in English | MEDLINE | ID: mdl-33539872

ABSTRACT

Neuropeptide Y is known to stimulate food intake in fish. In this study, we investigated tilapia NPY (tNPY) both for its effects on the growth of tilapia (Oreochromis niloticus, GIFT) in low fish meal and for its thermal stability. Three diets were formulated containing 0, 3 and 10 % fish meal (NF, LF and HF). From these diets, six experimental diets were prepared by spraying either tNPY solution (0.3 µg/g feed) or distilled water (DW) onto the surface of formulated feeds (NF + DW, NF + tNPY, LF + DW, LF + tNPY, HF + DW and HF + tNPY). Tilapia were fed the six experimental diets for 8 weeks. Fish in the NF + tNPY, LF + tNPY and HF + tNPY groups showed increasing trends in the weight gain rate and specific growth rate compared to its corresponding control group. The feed coefficient of group HF + tNPY was significantly lower than that of the control group. The growth performance of the LF + tNPY approached that of the HF + DW group. The mRNA levels of npy in NF + tNPY were significantly higher than those in NF + DW. A field experiment in which tNPY was sprayed in feeds by the vacuum spray method with doses of 0, 0.2 and 0.4 µg/g feed was performed for three months, and the FBW of tilapia receiving tNPY at 0.2 and 0.4 µg/g feed was higher than that of the control group although not significantly. The bioactivity of tNPY was confirmed by its ability to reduce cAMP levels and activate the ERK1/2 pathway. These results demonstrated that tNPY could promote tilapia growth with oral administration low fish meal diets.


Subject(s)
Animal Feed , Neuropeptide Y/genetics , Tilapia/growth & development , Weight Gain/genetics , Animals , Diet , Neuropeptide Y/metabolism , Tilapia/metabolism
8.
Virol J ; 17(1): 126, 2020 08 24.
Article in English | MEDLINE | ID: mdl-32831096

ABSTRACT

BACKGROUND: The incidence of Japanese encephalitis (JE) has been dramatically reduced in China after sufficient vaccine coverage. The live-attenuated Japanese encephalitis virus (JEV) vaccine SA14-14-2 is believed to have strongly contribute to this decrease. Another vaccine that seems to have decreased in importance is an inactivated vaccine based on the JEV P3 strain, which is considered to be modifiable, such as being transformed into a DNA vaccine to improve its immunogenicity. METHODS: In this study, the protective efficacy induced by the Japanese encephalitis DNA vaccine candidate pV-JP3ME encoding the premembrane (prM) and envelope (E) proteins of the P3 strain was assessed in BALB/c mice. The prM/E genes of the JEV P3 strain were subcloned into the vector pVAX1 (pV) to construct pV-JP3ME. RESULTS: The plasmid DNA was immunized into BALB/c mice, and high titers of IgG antibody and neutralizing antibody (nAb) against JEV were detected. The key cytokines in splenocytes were secreted upon stimulation with JEV antigens. Finally, complete protective efficacy was generated after challenge with the JEV P3 strain in the mice. CONCLUSIONS: The DNA vaccine pV-JP3ME based on the JEV P3 strain in this study can induce specific humoral immune and cytokine responses and provide complete protection against JEV in mice.


Subject(s)
Antibodies, Viral/blood , Encephalitis, Japanese/prevention & control , Japanese Encephalitis Vaccines/immunology , Vaccines, DNA/immunology , Animals , China , Chlorocebus aethiops , Cytokines/immunology , Encephalitis Virus, Japanese/classification , Encephalitis Virus, Japanese/genetics , Encephalitis Virus, Japanese/immunology , Encephalitis, Japanese/immunology , Female , Immunization , Japanese Encephalitis Vaccines/administration & dosage , Mice , Mice, Inbred BALB C , Plasmids/genetics , Specific Pathogen-Free Organisms , Vaccines, Inactivated/administration & dosage , Vaccines, Inactivated/immunology , Vero Cells
9.
Pancreas ; 49(7): 960-966, 2020 08.
Article in English | MEDLINE | ID: mdl-32658081

ABSTRACT

OBJECTIVES: The aim of this study was to investigate the changes of pancreatic microvascular vasomotion and blood distribution pattern in acute pancreatitis (AP), and whether Angiotensin (Ang)-(1-7) treatment could restore pancreatic microcirculation profiles. METHODS: Mice were randomly separated into control, AP, and Ang-(1-7)-treated AP (A-AP) group. Acute pancreatitis was induced in mice by intraperitoneal injection of cerulein and lipopolysaccharide. Pancreatitis was confirmed by histopathology, serum amylase, and high-sensitive C-reactive protein. Pancreatic microvascular vasomotion and blood distribution pattern in AP progression were assessed by laser Doppler. Meanwhile, ultrastructural changes of pancreatic microcirculation, including microvascular cavity and wall and endothelial mitochondria, were evaluated by transmission electron microscopy. RESULTS: Acute pancreatitis mice exhibited pathological pancreatic injuries with lower blood distribution pattern and decreased average blood perfusion, relative velocity, effective frequency, and amplitude of microvascular vasomotion. The pancreatic pathological injuries in Ang-(1-7)-treated mice were significantly alleviated. Consistently, Ang-(1-7) treatment led to a restoration in pancreatic microcirculation profiles. Furthermore, non-Ang-(1-7)-treated mice showed an irregular microvascular wall, narrow cavity, and swelling mitochondria, and these ultrastructural impairments were reversed by Ang-(1-7) administration. CONCLUSIONS: Pancreatic microcirculation profiles are abnormal in the progression of AP. Angiotensin-(1-7) administration could restore functional status of pancreatic microcirculation.


Subject(s)
Angiotensin I/pharmacology , Microcirculation/drug effects , Pancreas/blood supply , Pancreatitis/prevention & control , Peptide Fragments/pharmacology , Animals , Ceruletide , Endothelium, Vascular/cytology , Endothelium, Vascular/drug effects , Endothelium, Vascular/ultrastructure , Lipopolysaccharides , Male , Mice, Inbred C57BL , Microcirculation/physiology , Microscopy, Electron, Transmission , Pancreatitis/chemically induced , Pancreatitis/physiopathology
10.
Infect Genet Evol ; 85: 104443, 2020 11.
Article in English | MEDLINE | ID: mdl-32619637

ABSTRACT

Japanese encephalitis virus (JEV) is the causal pathogen of Japanese encephalitis (JE), which has become a severe public health problem and is one of the most rapidly spreading mosquito-borne diseases worldwide. Currently, there is no specific treatment for JEV. A vaccine would be an effective measure for reducing morbidity and mortality. Although the live attenuated vaccine SA14-14-2 has been approved in some countries, it is still necessary to develop safer, more effective, and less costly vaccines. In this study, a DNA vaccine candidate, pV-SA14ME, expressing the prM/E proteins of SA14-14-2 was inoculated into BALB/c mice via intramuscular electroporation, and the immunogenicity and degree of protection were evaluated. We found that administration of 50 µg pV-SA14ME via electroporation via three immunizations could induce persistent humoral and cellular immune responses and effectively protect mice against lethal JEV challenge. This study provides a basis for the subsequent promotion and use of the vaccine and lays the foundation for its further use in swine and humans.


Subject(s)
Encephalitis Virus, Japanese/immunology , Encephalitis, Japanese/immunology , Immunity , Vaccines, DNA/genetics , Vaccines, DNA/immunology , Viral Envelope Proteins/genetics , Viral Envelope Proteins/immunology , Animals , Antibodies, Viral/metabolism , Encephalitis Virus, Japanese/genetics , Encephalitis, Japanese/virology , Female , HEK293 Cells , Humans , Mice, Inbred BALB C , Vaccination , Vaccines, Attenuated , Vaccines, DNA/virology , Viral Envelope Proteins/metabolism
11.
Article in English | MEDLINE | ID: mdl-31849840

ABSTRACT

Background: Myostatin (Mstn), a member of the TGF-ß superfamily, is a negative regulator of skeletal muscle mass in mammals. Precise regulation of Mstn expression is important for somite growth in fish. MicroRNA (miRNA), a type of small non-coding RNA, regulates gene expression at the post-transcriptional level and participates in various physiological functions. A growing amount of evidence has emphasized the importance of miRNA in the development of skeletal muscle. Aims: This study aims to study how miRNAs regulate myostatin b (mstnb) post-transcriptionally in tilapia. Methods/Results: Mstnb 3' UTR sequences were obtained, and the results of tissue distribution showed that mstnb was expressed in several tissues, including brain, white muscle, gut, and adipose tissue. A total of 1,992 miRNAs were predicted to target mstnb in tilapia using bioinformatics, and a dual-luciferase reporter experiment confirmed that miR-181a/b-5p, miR-30-3p, miR-200a, and miR-27a were the target miRNAs of mstnb. Mutagenesis of the miR-181b-5p binding sites of mstnb significantly increased the luciferase signal compared to the wild-type mstnb. In tilapia primary muscle cells, overexpression of miR-181b-5p led to the downregulation of MSTNb expression, and the inhibitory effect of MSTNb on the downstream genes was dismissed, while inhibition of miR-181b-5p could reverse these phenomena. Conclusion: Taken together, our results suggested that miR-181b-5p could promote the growth of skeletal muscle by decreasing the MSTNb protein level in tilapia.

12.
Pancreas ; 47(7): 892-897, 2018 08.
Article in English | MEDLINE | ID: mdl-29912852

ABSTRACT

OBJECTIVES: The aim of this study was to investigate the effects of emodin on attenuating autophagy response in acute pancreatitis (AP) models. METHODS: Acute pancreatitis was induced in Wistar rats by injecting 3% sodium taurocholate into the biliopancreatic duct. Emodin (40 mg/kg per day) was then given intragastrically, administrated 2 hours after AP induction. Rats were killed 24 hours after AP induction. The pancreatic injury was assessed using biochemical and histological approaches. Autophagosomes in pancreatic acinar cells were observed by electron microscopy. The expression levels of microtubule-associated protein 1 light chain 3 (LC3) B/A, beclin-1, and p62/SQSTM1 (p62) were detected by Western blotting, quantitative real-time polymerase chain reaction, and immunohistochemistry in pancreatic tissues. RESULTS: Compared with non-emodin-treated rats, the pathological injuries of the pancreas of emodin-treated rats were significantly alleviated, and autophagy vacuole formation was reduced within pancreatic acinar cells. Administration of emodin led to a reduction in the autophagy-associated protein level of LC3 (B/A) and p62 but not beclin-1. The transcript levels of LC3B, beclin-1, and p62 were decreased in the emodin-treated rats compared with non-emodin-treated rats. CONCLUSIONS: Our data demonstrate that emodin plays a critical role in ameliorating AP, possibly by down-regulating autophagic protein levels.


Subject(s)
Autophagy/drug effects , Emodin/pharmacology , Pancreas/drug effects , Pancreatitis/prevention & control , Acute Disease , Animals , Beclin-1/genetics , Beclin-1/metabolism , Gene Expression/drug effects , Male , Microtubule-Associated Proteins/genetics , Microtubule-Associated Proteins/metabolism , Pancreas/metabolism , Pancreas/pathology , Pancreatitis/chemically induced , Pancreatitis/genetics , Protective Agents/pharmacology , Protein Kinase Inhibitors/pharmacology , Rats, Wistar , Sequestosome-1 Protein/genetics , Sequestosome-1 Protein/metabolism , Taurocholic Acid
13.
Biochem Biophys Res Commun ; 499(2): 285-290, 2018 05 05.
Article in English | MEDLINE | ID: mdl-29574160

ABSTRACT

Compensatory growth (CG) is defined as a phase of accelerated growth when the disadvantageous environment is improved, accompanied by metabolic adjustment. Here, we report that hepatic oxidative phosphorylation (OXPHOS) activity was enhanced during compensatory growth in zebrafish. Mitochondrial metabolism enabled the generation of reactive oxygen species (ROS), which activated the nrf2 (nuclear factor-erythroid 2-related factor 2) signaling pathway, as well as the mTOR signaling pathway. Tempol (a superoxide dismutase mimetic) treatment blocked ROS signaling in the liver as well as CG in zebrafish. These results demonstrated that mitochondrial ROS signaling are essential for the occurrence of compensatory growth in zebrafish.


Subject(s)
Liver/physiology , Reactive Oxygen Species/metabolism , Zebrafish/growth & development , Zebrafish/metabolism , Animals , Cyclic N-Oxides/pharmacology , Feeding Behavior/drug effects , Female , Intestinal Mucosa/metabolism , Intestines/drug effects , Liver/drug effects , Mitochondria, Liver/drug effects , Mitochondria, Liver/metabolism , Muscle Fibers, Skeletal/drug effects , Muscle Fibers, Skeletal/metabolism , Oxidative Phosphorylation/drug effects , Signal Transduction/drug effects , Spin Labels
14.
BMC Complement Altern Med ; 18(1): 52, 2018 Feb 05.
Article in English | MEDLINE | ID: mdl-29402324

ABSTRACT

BACKGROUND: This study was to evaluate the effects of herbal compound 861 (Cpd861) on ski-related novel protein N (SnoN) and transforming growth factor-ß1 (TGF-ß1) /Smad signaling in rats with bile duct ligation (BDL)-induced hepatic fibrosis, and to explore the mechanisms of Cpd861 on hepatic fibrosis. METHODS: Thirty Wistar male rats were randomly divided into three groups: sham operation, BDL, and Cpd861. To induce hepatic fibrosis, BDL and Cpd861 group rats underwent bile duct ligation. Cpd861 at 9 g/kg/d or an equal volume of normal saline was administered intragastrically for 28 days. Liver injury was assessed biochemically and histologically. Protein and mRNA changes for SnoN and TGF-ß1/Smad signaling (TGF-ß1, Smad2, phosphorylated Smad2 [p-Smad2], phosphorylated Smad3 [p-Smad3], fibronectin, and collagen III) were determined by Western blotting and quantitative real-time PCR. RESULTS: BDL rats treated with Cpd861 had significantly alleviated hepatic fibrosis compared to BDL rats not receiving Cpd861 treatment. Moreover, Cpd861 decreased the expression of fibrosis-associated proteins fibronectin and collagen III in liver tissue. Cpd861 administration increased the expression of SnoN protein, did not change SnoN mRNA level, and decreased TGF-ß1, p-Smad2, and p-Smad3 protein expression compared to BDL without Cpd861 treatment. CONCLUSIONS: Cpd861 attenuates hepatic fibrosis by increasing SnoN protein expression and inhibiting the TGF-ß1/Smad signaling pathway.


Subject(s)
Drugs, Chinese Herbal/pharmacology , Liver Cirrhosis/metabolism , Nerve Tissue Proteins/metabolism , Signal Transduction/drug effects , Smad Proteins/metabolism , Transcription Factors/metabolism , Transforming Growth Factor beta1/metabolism , Animals , Bile Ducts/injuries , Bile Ducts/surgery , Disease Models, Animal , Immunohistochemistry , Liver/chemistry , Liver/drug effects , Liver/metabolism , Male , Nerve Tissue Proteins/analysis , Nerve Tissue Proteins/genetics , Rats , Rats, Wistar , Smad Proteins/analysis , Smad Proteins/genetics , Transcription Factors/analysis , Transcription Factors/genetics , Transforming Growth Factor beta1/analysis , Transforming Growth Factor beta1/genetics
15.
Int J Mol Med ; 41(3): 1315-1322, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29286088

ABSTRACT

Arkadia is able to degrade key signaling molecules in the transforming growth factor (TGF)­ß1 signaling pathway; however, the expression of Arkadia in the liver during development and progression of TGF­ß1/Smad signaling­regulated hepatic fibrosis remains to be elucidated. The present study aimed to examine Arkadia expression in the livers of two rat models of hepatic fibrosis induced by bile duct ligation and carbon tetrachloride intoxication, and in human liver samples from patients with hepatic fibrosis. Expression was analyzed by quantitative polymerase chain reaction, immunohistochemistry and western blot analysis. The results indicated that Arkadia was predominantly expressed in the cytoplasm of cholangiocytes and hepatocytes. The protein expression levels of Arkadia were significantly decreased in fibrotic livers, whereas the mRNA expression levels of Arkadia were significantly increased in fibrotic livers compared with in nonfibrotic livers. In conclusion, these data indicated that Arkadia may regulate the pathogenesis and progression of hepatic fibrosis.


Subject(s)
Disease Progression , Liver Cirrhosis/metabolism , Liver Cirrhosis/pathology , Liver/metabolism , Liver/pathology , Nuclear Proteins/metabolism , Ubiquitin-Protein Ligases/metabolism , Adult , Animals , Bile Ducts/pathology , Carbon Tetrachloride , Female , Humans , Ligation , Liver/physiopathology , Liver Cirrhosis/physiopathology , Male , Rats, Wistar , Young Adult
16.
Int J Mol Med ; 41(1): 409-420, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29138810

ABSTRACT

The aim of the present study was to investigate the role of the angiotensin-converting enzyme (ACE)2-angiotensin­(Ang)-(1-7)-Mas axis in the pathogenesis of pancreatitis and the association between this axis and the p38 mitogen-activated protein kinase (p38 MAPK)/nuclear factor (NF-κB) signaling pathway in pancreatic acinar cells. Mouse pancreatic acinar cancer (MPC-83) cells were stimulated with 10 nM caerulein (CAE) to create an in vitro model of acute pancreatitis, and collected for analysis at 2, 6, 12, 24 and 48 h post stimulation. In addition, cells were pretreated with different concentrations of Ang­(1­7), Ang­(1­7) antagonist A779, p38 MAPK inhibitor SB203580 or ACE2 inhibitor DX600 for 30 min, and then stimulated with CAE for 24 h. The ACE2, Mas receptor, p38 MAPK, phosphorylated (p)-p38 MAPK and NF-κB expression levels were evaluated using western blotting and immunofluorescence. p38 MAPK, NF-κB, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-8 and IL-10 mRNA expression levels were assessed using reverse transcription-quantitative polymerase chain reaction. The results of the immunofluorescence assay demonstrated that ACE2 and p38 MAPK were present mainly in the cytoplasm, while the Mas receptor was located mainly in the cell membrane. ACE2, p38 MAPK and p-p38 MAPK protein levels were significantly increased (P<0.05) following stimulation with CAE compared with those in the control group and peaked at 24 h. Mas receptor protein levels were significantly upregulated (P<0.05) between 6 and 24 h, peaking at 12 h. Ang­(1­7) and SB203580 downregulated p-p38 MAPK and NF-κB expression and the mRNA levels of inflammatory factors IL-6, TNF-α and IL-8, but upregulated the mRNA level of inflammatory factor IL-10 compared with those treated with CAE alone. These results were supported by the opposite outcomes observed for cells treated with A779 or DX600. Therefore, it was concluded that the ACE2-Ang­(1­7)-Mas axis significantly inhibits pancreatitis by inhibition of the p38 MAPK/NF-κB signaling pathway.


Subject(s)
Inflammation/drug therapy , Peptidyl-Dipeptidase A/genetics , Proto-Oncogene Proteins/genetics , Receptors, G-Protein-Coupled/genetics , p38 Mitogen-Activated Protein Kinases/genetics , Acinar Cells/drug effects , Acinar Cells/pathology , Angiotensin I/antagonists & inhibitors , Angiotensin I/genetics , Angiotensin II/administration & dosage , Angiotensin II/analogs & derivatives , Angiotensin-Converting Enzyme 2 , Animals , Humans , Imidazoles/administration & dosage , Inflammation/genetics , Inflammation/pathology , Mice , NF-kappa B/genetics , Pancreas/drug effects , Pancreas/pathology , Peptide Fragments/administration & dosage , Peptide Fragments/antagonists & inhibitors , Peptide Fragments/genetics , Peptides/administration & dosage , Peptidyl-Dipeptidase A/drug effects , Proto-Oncogene Mas , Proto-Oncogene Proteins/antagonists & inhibitors , Pyridines/administration & dosage , Receptors, G-Protein-Coupled/antagonists & inhibitors , Signal Transduction/drug effects
17.
Mol Med Rep ; 16(3): 3455-3460, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28713987

ABSTRACT

Extensive apoptosis of pancreatic acinar cells frequently occurs in acute pancreatitis (AP), and has been identified to be closely associated with the decrease of pancreatic parenchymal cells and pancreatic damage. The present study aimed to investigate the possible effect of angiotensin (Ang)­(1­7) on caerulein (CAE)­induced pancreatic acinar cell apoptosis. Mouse pancreatic acinar cancer cells (MPC­83) were divided into 4 groups: Control group; CAE group; CAE + Ang­(1­7) group; and CAE + Ang­(1­7) antagonist (A779) group. The control group consisted of normal MPC­83 cells without special treatment. The CAE group was stimulated with 10 nmol/l CAE and harvested at 2, 6, 12, 24 and 48 h. For the CAE + Ang­(1­7) group and CAE + A779 group, the CAE­induced pancreatic acinar cells were mock pretreated or pretreated with different concentrations of Ang­(1­7) or A779 (10­7, 10­6 or 10­5 mol/l) for 30 min. Caspase­3 is a critical executioner of apoptosis, as it is either partly or completely responsible for the proteolytic cleavage of numerous key proteins including the nuclear enzyme poly (ADP­ribose) polymerase. Activation of caspase­3 requires proteolytic processing of its inactive zymogen into activated p17 and p12 fragments. Thus, the present study investigated the apoptotic markers, including cleaved caspase­3, B­cell lymphoma 2 (Bcl­2), Bcl­2­like protein 4 (Bax) and renin­angiotensin system (RAS) pathway related proteins (ACE2 and Mas receptor). The results demonstrated that the cleaved caspase­3 levels were increased in the CAE group (P<0.05), peaking at 24 h, and declined when incubated with Ang­(1­7). Following treatment with Ang­(1­7), levels of the anti­apoptotic protein Bcl­2 rose dramatically in a dose­dependent manner. The ratio of the pro­apoptotic protein Bax to the anti­apoptotic protein Bcl­2 dropped notably, which demonstrated a tendency towards curbing apoptosis. In addition, the cleaved caspase­3 levels, and the ratio of Bax to Bcl­2 in the CAE + A779 group presented a significant rise compared with the CAE group. It was concluded that Ang­(1­7) may possess an inhibitory effect on CAE­induced pancreatic acinar cell apoptosis and that appropriate interventions in RAS may attenuate pancreatic injury during AP.


Subject(s)
Acinar Cells/pathology , Angiotensin I/pharmacology , Apoptosis/drug effects , Ceruletide/toxicity , Pancreas/pathology , Peptide Fragments/pharmacology , Acinar Cells/metabolism , Angiotensin II/analogs & derivatives , Angiotensin II/pharmacology , Angiotensin-Converting Enzyme 2 , Animals , Caspase 3/metabolism , Mice , Peptidyl-Dipeptidase A/metabolism , Proto-Oncogene Mas , Proto-Oncogene Proteins/metabolism , Receptors, G-Protein-Coupled/metabolism , bcl-2-Associated X Protein/metabolism
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