Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 6 de 6
Filtrar
1.
Hum Cell ; 37(4): 972-985, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38656742

RESUMEN

Acute coronary artery blockage leads to acute myocardial infarction (AMI). Cardiomyocytes are terminally differentiated cells that rarely divide. Treatments preventing cardiomyocyte loss during AMI have a high therapeutic benefit. Accumulating evidence shows that microRNAs (miRNAs) may play an essential role in cardiovascular diseases. This study aims to explore the biological function and underlying regulatory molecular mechanism of miR-322-5p on myocardial infarction (MI). This study's miR-322-5p is downregulated in MI-injured hearts according to integrative bioinformatics and experimental analyses. In the MI rat model, miR-322-5p overexpression partially eliminated MI-induced changes in myocardial enzymes and oxidative stress markers, improved MI-caused impairment on cardiac functions, inhibited myocardial apoptosis, attenuated MI-caused alterations in TGF-ß, p-Smad2, p-Smad4, and Smad7 protein levels. In oxygen-glucose deprivation (OGD)-injured H9c2 cells, miR-322-5p overexpression partially rescued OGD-inhibited cell viability and attenuated OGD-caused alterations in the TGF-ß/Smad signaling. miR-322-5p directly targeted Smurf2 and inhibited Smurf2 expression. In OGD-injured H9c2 cells, Smurf2 knockdown exerted similar effects to miR-322-5p overexpression upon cell viability and TGF-ß/Smad signaling; moreover, Smurf2 knockdown partially attenuated miR-322-5p inhibition effects on OGD-injured H9c2 cells. In conclusion, miR-322-5p is downregulated in MI rat heart and OGD-stimulated rat cardiomyocytes; the miR-322-5p/Smurf2 axis improves OGD-inhibited cardiomyocyte cell viability and MI-induced cardiac injuries and dysfunction through the TGF-ß/Smad signaling.


Asunto(s)
MicroARNs , Infarto del Miocardio , Miocitos Cardíacos , Transducción de Señal , Factor de Crecimiento Transformador beta , Ubiquitina-Proteína Ligasas , MicroARNs/genética , MicroARNs/metabolismo , MicroARNs/fisiología , Infarto del Miocardio/genética , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Animales , Transducción de Señal/genética , Transducción de Señal/fisiología , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/fisiología , Factor de Crecimiento Transformador beta/metabolismo , Ratas , Miocitos Cardíacos/metabolismo , Modelos Animales de Enfermedad , Proteína Smad2/metabolismo , Proteína Smad2/genética , Expresión Génica/genética , Masculino , Regulación hacia Abajo/genética , Ratas Sprague-Dawley , Apoptosis/genética , Proteínas Smad/metabolismo , Glucosa/metabolismo , Proteína Smad4/metabolismo , Proteína Smad4/genética , Terapia Molecular Dirigida , Proteína smad7/metabolismo , Proteína smad7/genética
2.
Naunyn Schmiedebergs Arch Pharmacol ; 396(12): 3797-3807, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37347266

RESUMEN

Acute lung injury (ALI) and sepsis are complicated syndromes that are often left untreated in critically ill patients. 6-Gingerol is a phenolic phytochemical compound that is found in fresh ginger, has pharmacological effects against inflammation. This study explored the roles of 6-gingerol in a mouse model of acute lung injury caused by lipopolysaccharide (LPS) and RAW-264.7 cells inflammation. The LPS-induced animal model underwent histopathological examinations, and RAW-264.7 cells viability was determined by Cell counting Kit-8 (CCk-8) assay. Additionally, qRT-PCR, Immunofluorescence, Western blot, and ELISA were used in vivo and in vitro to identify inflammatory factors and proteins associated with NF-κB and MAPK signaling pathways. In a histological examination 6-gingerol exhibited protective effects. Moreover, 6-gingerol elevated cell viability and downregulated inflammatory factors Interlukin-1ß (IL-1ß), Interlukin-6 (IL-6) and Tumor necrosis factor-α (TNF-α) in LPS-treated RAW-264.7 cells. Furthermore, 6-gingerol decreased phosphorylation of P65, P38 and the level of JNK in NF-κB and MAPK pathways. Importantly, 6-gingerol increased transcript abundance of miR-322-5p which suppressed by LPS and miR-322-5p downregulation negated the protective functions of 6-gingerol. The protective activity of 6-gingerol was mediated by miR-322-5p up-regulation.


Asunto(s)
Lesión Pulmonar Aguda , MicroARNs , Humanos , Ratones , Animales , FN-kappa B/metabolismo , Lipopolisacáridos/toxicidad , Transducción de Señal , MicroARNs/genética , MicroARNs/metabolismo , Células RAW 264.7 , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/genética , Lesión Pulmonar Aguda/patología
3.
Nefrologia (Engl Ed) ; 43 Suppl 2: 8-20, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37179213

RESUMEN

INTRODUCTION AND OBJECTIVES: Acute kidney injury (AKI) is a common devastating complication characterized by an abrupt loss of renal function. It is of great significance to explore promising biomarkers for AKI treatment. MATERIALS AND METHODS: Here, we established LPS (lipopolysaccharide)-induced AKI mice models and LPS-induced AKI mouse renal tubular epithelial cell model. The severity of AKI was determined by the levels of BUN (blood urea nitrogen) and SCr (serum creatinine), the observation of pathological section as well as the renal tubular injury score. The apoptosis was determined by the measurement of Caspase-3 and Caspase-9 activities, and cell apoptosis assays. qRT-PCR (quantitative real-time PCR) and western blot revealed that miR-322-5p (microRNA-322-5p) was up-regulated in LPS -induced AKI models while Tbx21 (T-box transcription factor 21) was down-regulated in LPS-induced AKI models. Dual-luciferase reporter and RNA pulldown assays detected the interaction of Tbx21 with miR-322-5p. RESULTS: We found that miR-322-5p was overtly over-expressed in the in vitro LPS-induced AKI model and promoted the apoptosis of AKI mouse renal tubular epithelial cells via inhibiting Tbx21, which suppressed the mitochondrial fission and cell apoptosis through MAPK/ERK (mitogen-activated protein kinase/extracellular signal-related kinase) pathway. CONCLUSIONS: We demonstrated that miR-322-5p promotes LPS-induced mouse AKI by regulating Tbx21/MAPK/ERK axis, which might provide new sights for AKI research.


Asunto(s)
Lesión Renal Aguda , MicroARNs , Ratones , Animales , Lipopolisacáridos/efectos adversos , Proteínas Quinasas Activadas por Mitógenos , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/genética , Lesión Renal Aguda/metabolismo , MicroARNs/genética , Células Epiteliales/metabolismo , Células Epiteliales/patología , Factores de Transcripción
4.
Cell Cycle ; 21(24): 2635-2650, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35957539

RESUMEN

Liver injury from any number of causes (e.g. chemical material, drugs and diet, viral infection) is a global health problem, and its mechanism is not clearly understood. MicroRNAs (miRNAs) expression profiling is gaining popularity because miRNAs, as key regulators in gene expression networks, can influence many biological processes and have also shown promise as biomarkers for disease. Previous studies reported the regulation effects of miRNAs in liver injury, whereas function and molecular mechanisms of miR-322-5p were still unclear. Therefore, our study focused on the biological role of miR-322-5p in carbon tetrachloride (CCl4)-induced liver injury proliferation, apoptosis, and cell cycle. A mouse model of CCl4-induced liver injury was established, and the transcriptomes and miRNAs transcriptomes of 2d and 5d liver tissues after injury were sequenced. The expression of miR-322-5p and the cell cycle genes were detected in liver tissues and Hepa1-6 cell line by miRNA RT-PCR, qRT-PCR. The effects of miR-322-5p on liver cell proliferation, cell cycle and apoptosis were evaluated using MTS assays and flow cytometry analysis. The relationship between miR-322-5p and Wee1 was predicted and confirmed by bioinformatics analysis and a dual luciferase reporter assay. Functional experiments, including an MTS assay and flow cytometric analysis, were performed to study the effects of Wee1. MiR-322-5p was upregulated in injury liver tissues, and downregulated miR-322-5p was proved to inhibit proliferation, apoptosis and arrest cell cycle at G2/M in vitro. The dual-luciferase reporter assay results indicated that miR-322-5p has a binding site at position 285 in the Wee1 3´UTR. The effects of miR-322-5p in proliferation and cell cycle regulation can be abolished by Wee1 through rescue experiments. By directly targeting Wee1 influenced the expression of several cell cycle factors, including Cyclin dependent kinase 1 (Cdk1), cyclin B1 (Ccnb1) and Cell division cyclin 25C (Cdc25C). MiR-322-5p may function as a suppressive factor by negatively controlling Wee1, thus, highlighting the potential role of miR-322-5p as a therapeutic target for liver injury.Abbreviations: ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; GSH: Glutathione, γ-glutamyl cysteinel + glycine; CCl4: Carbon tetrachloride; HE: Haematoxylin and eosin; KEGG: Kyoto Encyclopedia of Genes and Genomes.


Asunto(s)
Enfermedad Hepática Crónica Inducida por Sustancias y Drogas , MicroARNs , Ratones , Animales , Regulación Neoplásica de la Expresión Génica , Tetracloruro de Carbono/toxicidad , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/genética , Línea Celular Tumoral , Proliferación Celular/genética , Ciclo Celular/genética , Apoptosis/genética , MicroARNs/genética , MicroARNs/metabolismo , División Celular
5.
Open Med (Wars) ; 17(1): 907-914, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35647304

RESUMEN

This study aimed to determine whether microRNA-322-5p regulates seizure and seizure damage by targeting the TLR4/TRAF6/NF-κB-associated inflammatory signaling pathway. In a pilocarpine-induced epileptic rat model, the expressions of miR-322-5p, TLR4, NF-κB, TRAF6, IRF5, IL-1ß, and GABA were assessed by a quantitative polymerase chain reaction and western blotting. Tunel detects hippocampal neuron apoptosis. The results showed that the expression of miR-322-5p significantly decreased in status epilepticus (SE) rats. The reduction of miR-322-5p was accompanied by increased levels of pro-inflammatory cytokines, an increased NF-κB expression, and reduced γ-aminobutyric acid (GABA) levels. Exogenous miR-322-5p reduced the expression of inflammatory molecules and increased the GABA levels in SE rats, and also reduced hippocampal neuronal cell apoptosis caused by epilepsy. In conclusion, the miR-322-5p significantly inhibited the TLR4/TRAF6/NF-κB-associated inflammation and reduced neuronal apoptosis, suggesting that its induction may be of potential interest for novel antiseizure medications.

6.
Yonsei Med J ; 63(3): 282-291, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35184431

RESUMEN

PURPOSE: As the population ages, the incidence of clinical dementia has been rising around the world. It has been reported that microRNAs act as key diagnostic biomarkers and targets for various neurological conditions, including dementia. MiR-322-5p has been revealed to play an important role in multiple diseases. In this study, we aimed to investigate the role and regulatory mechanism of miR-322-5p in vascular dementia. MATERIALS AND METHODS: In this study, neonatal rat neurons (NRNs) were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) to induce cell injury. The animals were subjected to permanent bilateral occlusion of the carotid arteries (2-vessel occlusion, 2VO) to induce the model of chronic brain hypoperfusion. RESULTS: MiR-322-5p expression was significantly downregulated in the neurons exposed to OGD/R and the hippocampi of 2VO rats. Overexpression of miR-322-5p ameliorated cell apoptosis and the inflammatory response in vitro. In a mechanistic study, miR-322-5p was confirmed to directly target and negatively regulate tetraspanin 5 (TSPAN5) in cultured NRNs. Moreover, overexpression of TSPAN5 could counteract the effects of miR-322-5p overexpression on cell apoptosis and the inflammatory response in OGD/R-treated neurons. More importantly, miR-322-5p improved cognitive ability and inhibited inflammatory production in 2VO rats. CONCLUSION: Overall, the results suggest that miR-322-5p alleviates vascular dementia development by targeting TSPAN5. This discovery may provide a potential therapeutic target for dementia.


Asunto(s)
Isquemia Encefálica , Demencia Vascular , MicroARNs , Daño por Reperfusión , Animales , Apoptosis/genética , Cognición , Demencia Vascular/genética , Glucosa/farmacología , MicroARNs/metabolismo , Ratas , Daño por Reperfusión/metabolismo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA