RESUMO
Diabetic nephropathy (DN) accompanied by cardiac fibrosis (CF) increases the mortality rate among people with diabetes. This study sought to explore the molecular mechanism of long non-coding RNA X inactive specific transcript (lncRNA XIST) in CF in DN mice. The animal model of DN was established by streptozocin (STZ). The levels of lncRNA XIST, microRNA (miR)-106a-5p, and RUNX family transcription factor 1 (RUNX1) were determined by quantitative real-time polymerase chain reaction (qRT-PCR), followed by biochemical analysis, hematoxylin & eosin and Masson staining, echocardiography, and quantification of collagen I, collagen III, α-smooth muscle actin (α-SMA), and transforming growth factor-ß1 (TGF-ß1) levels through qRT-PCR and Western blot assay. The subcellular localization of lncRNA XIST was analyzed by nuclear/cytoplasmic fractionation assay and the bindings of miR-106a-5p to lncRNA XIST and RUNX1 were confirmed by RNA immunoprecipitation and dual-luciferase assays. Functional rescue experiments were performed to validate the role of miR-106a-5p/RUNX1 in CF in DN mice. lncRNA XIST and RUNX1 were elevated while miR-106a-5p was decreased in STZ mice. lncRNA XIST inhibition reduced myocardial injury and collagen deposition, along with decreased levels of fasting blood glucose, serum creatinine, blood urea nitrogen, and urinary microalbumin, collagen I, collagen III, α-SMA, and TGF-ß1. lncRNA XIST competitively bound to miR-106a-5p to promote RUNX1 transcription. miR-106a-5p downregulation or RUXN1 upregulation reversed the protective role of lncRNA XIST inhibition in STZ mice. lncRNA XIST competitively bound to miR-106a-5p to promote RUNX1 transcription, thereby aggravating renal dysfunction and CF in DN mice.
Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , MicroRNAs , RNA Longo não Codificante , Animais , Camundongos , MicroRNAs/metabolismo , Nefropatias Diabéticas/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fator de Crescimento Transformador beta1 , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Fibrose , Proliferação de Células/genéticaRESUMO
BACKGROUND: Diabetic nephropathy (DN) remains the most prevalent cause of end-stage renal disease. Nuclear receptor subfamily 4 group A member 2 (NR4A2) is a nuclear receptor with unique physiological characteristics. OBJECTIVE: This study explored the molecular mechanism of NR4A2 in renal and cardiac functions of DN rats. METHODS: A rat model of DN was established by intraperitoneal injection of streptozocin. NR4A2, histone deacetylase 11 (HDAC11), and sprouty 1 (SPRY1) expressions were detected. The fasting blood glucose (FBG), urinary albumin (UAlb), serum creatinine (Cr), and blood urea nitrogen (BUN) were determined. The pathological injury of renal and myocardial tissues was evaluated. The mitral early to late diastolic flow velocity ratio (E/A ratio), left ventricular ejection fraction (LVEF), left ventricular systolic function (LVSF), left ventricular internal dimension systole (LVIDs), and left ventricular internal diameter diastole (LVIDd) were tested, and the levels of serum cardiac troponin I (cTnI) and creatine kinase-MB (CK-MB) were examined. The enrichment of NR4A2 in HDAC11 promoter and enrichment of H3K27 acetylation in SPRY1 promoter were measured. RESULTS: NR4A2 and SPRY1 were downregulated while HDAC11 was upregulated in renal and myocardial tissues of DN rats. NR4A2 overexpression reduced FBG, UAlb, Cr, and BUN, alleviated pathological injury of renal and myocardial tissues, elevated the E/A ratio, LVEF, and LVFS, but reduced LVIDs, and decreased serum cTnI and CK-MB. NR4A2 depressed HDAC11 expression by binding to the HDAC11 promoter. HDAC11 repressed SPRY1 transcription by suppressing the H3K27ac level. HDAC11 overexpression or SPRY1 inhibition reversed the alleviating effect of NR4A2 overexpression on DN rats. CONCLUSION: NR4A2 was poorly expressed in DN rats. NR4A2 overexpression suppressed HDAC11 expression by binding to the HDAC11 promoter and enhanced SPRY1 transcription by enhancing H3K27 acetylation, thereby alleviating the renal and myocardial injury of DN rats.
RESUMO
BACKGROUND: Pyogenic liver abscesses are insidious in the early stage. Some cases progress rapidly, and the patient's condition can worsen and even become life-threatening if timely treatment is not provided. Surgery and prolonged antibiotic treatment are often required if the abscess is large and liquefied and becomes separated within the lumen. CASE SUMMARY: We report a case of bacterial liver abscess with a poor outcome following pharmacological treatment, review the literature related to the use of platelet-rich plasma (PRP) in the treatment of hepatic impairment and partial hepatectomy in animals, and discuss the prognostic features of surgical incision and drainage combined with PRP in the treatment of bacterial liver abscesses. This is the first case describing the use of PRP in the treatment of a bacterial liver abscess in humans, providing new ideas for the treatment of this condition. CONCLUSION: This case highlights the importance of surgical treatment for bacterial liver abscesses that are well liquefied and poorly managed medically. PRP may produce antimicrobial effects and promote the regeneration and repair of liver tissue.
RESUMO
Venous congestion and volume overload are important in cardiorenal syndromes, in which multiple regulated factors are involved, including long noncoding RNAs (lncRNAs). To investigate the underlying role of lncRNAs in regulating the development of venous congestion, an Affymetrix microarray associated with peripheral venous congestion was annotated, then a bipartite dynamic lncRNA-mRNA co-expression network was constructed in which nodes indicated lncRNAs or mRNAs. The nodes were connected when the lncRNAs or mRNAs were dynamically coexpressed. Following functional analysis of this network, several dynamic alternative pathways were identified, including the calcium signaling pathway during venous congestion development. Additionally, certain lncRNAs (LINC00523, LINC01210 and RP11-435O5.5) were identified that may potentially dynamically regulate certain proteins, including plasma membrane calcium ATPase (PMCA) and G proteincoupled receptor (GPCR), in the calcium signaling pathway. Particularly, the dynamically regulated switch of LINC00523 from coexpression with PMCA to GPCR may be involved in damage to steady state intracellular calcium. In brief, the current study demonstrated a potential novel mechanism of lncRNA function during venous congestion.
Assuntos
Regulação da Expressão Gênica , Redes Reguladoras de Genes , Hiperemia/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Ontologia Genética , Humanos , Hiperemia/metabolismo , Anotação de Sequência Molecular , Transdução de SinaisRESUMO
Increasing evidence has demonstrated that the activation of heme oxygenase (HO)1 reduces autophagy stimulated by oxidative stress injury, in which the supraphysiological production of reactive oxygen species (ROS) is detected. However, the potential mechanism underlying this effect remains unclear. The present study aimed to investigate the function of HO1 activation in the regulation of autophagy in glomerular mesangial cells subjected to H2O2induced oxidative stress injury. The results demonstrated that the HO1 agonist, hemin, reduces the LC3 protein level, which was enhanced by H2O2 treatment. Furthermore, heminactivated HO1 may function as a regulator of oxidative stressinduced autophagy in a dosedependent manner. Pharmacological activation of cJun Nterminal kinase (JNK) inhibited the effect of hemin, indicating that the JNK signaling pathway is associated with the mechanism of HO1 in impeding excessive autophagy. In addition to successfully alleviating H2O2induced oxidative stress and cellular apoptosis, heminactivated HO1 may provide cytoprotection against rapamycin, a specific autophagy agonist. The present result suggested the inhibitory action of HO1 in the avoidance of a potentially enhanced linkage between autophagy and apoptosis, particularly in the setting of excessive ROS. Therefore, enhancing the intracellular activity of HO1 may assist the crosstalk between oxidative stress, autophagy and apoptosis, and represent a novel therapeutic strategy for renal ischemic disease.