RESUMEN
Septic cardiomyopathy (SCM) is one of the most serious complications of sepsis. The present study investigated the role and mechanism of upstream stimulatory factor 2 (USF2) in SCM. Serum samples were extracted from SCM patients and healthy individuals. A murine model of sepsis was induced by caecal ligation and puncture (CLP) surgery. Myocardial injury was examined by echocardiography and HE staining. ELISA assay evaluated myocardial markers (CK-MB, cTnI) and inflammatory cytokines (TNF-α, IL-1ß, IL-18). Primary mouse cardiomyocytes were treated with lipopolysaccharide (LPS) to simulate sepsis in vitro. RT-qPCR and Western blot were used for analyzing gene and protein levels. CCK-8 assay assessed cell viability. NLRP3 was detected by immunofluorescence. ChIP, RIP and dual luciferase reporter assays were conducted to validate the molecular associations. USF2 was increased in serum from SCM patients, septic mice and primary cardiomyocytes. USF2 silencing improved the survival of septic mice and attenuated sepsis-induced myocardial pyroptosis and inflammation in vitro and in vivo. Mechanistically, USF2 could directly bind to the promoter of miR-206 to transcriptionally inhibit its expression. Moreover, RhoB was confirmed as a target of miR-206 and could promote ROCK activation and NLRP3 inflammasome formation. Moreover, overexpression of RhoB remarkably reversed the protection against LPS-induced inflammation and pyroptosis mediated by USF2 deletion or miR-206 overexpression in cardiomyocytes. The above findings elucidated that USF2 knockdown exerted a cardioprotective effect on sepsis by decreasing pyroptosis and inflammation via miR-206/RhoB/ROCK pathway, suggesting that USF2 may be a novel drug target in SCM.
RESUMEN
Immune cell infiltration plays a key role in acute kidney injury (AKI) to chronic kidney disease (CKD) progression. T lymphocytes, neutrophils, monocytes/macrophages and other immune cells regulate inflammation, tissue remodelling and repair. To determine the kinetics of accumulation of various immune cell populations, we established an animal model combining parabiosis and separation surgery to explore the fate and lifespan of peripheral leucocytes that migrate to the kidney. We found that peripheral T lymphocytes could survive for a long time (more than 14 days), whereas peripheral neutrophils survived for a short time in both healthy and ischaemia-induced damaged kidneys. Nearly half of the peripheral-derived macrophages disappeared after 14 days in normal kidneys, while their existing time in the inflammatory kidneys was prolonged. A fraction of F4/80high macrophages were renewed from the circulating monocyte pool. In addition, we found that after renal ischaemia reperfusion, neutrophils increased significantly in the early phase, and T lymphocytes mainly accumulated in the late stage, whereas macrophages infiltrated throughout AKI-CKD progression and were sustained longer in injured as opposed to normal kidneys. In conclusion, peripheral-derived macrophages, T lymphocytes and neutrophils exhibit different lifespans in the kidney, which may play different roles during AKI-CKD progression.
Asunto(s)
Lesión Renal Aguda/etiología , Lesión Renal Aguda/metabolismo , Sistema Inmunológico/citología , Sistema Inmunológico/fisiología , Isquemia/complicaciones , Riñón/inmunología , Longevidad , Parabiosis , Lesión Renal Aguda/patología , Animales , Biomarcadores , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Expresión Génica , Inmunohistoquímica , Linfocitos/inmunología , Linfocitos/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismo , Masculino , Ratones , Neutrófilos/inmunología , Neutrófilos/metabolismoRESUMEN
Via the employment of a mixed-ligand method, a novel Pb(II)-coordination polymer with the chemical formula of [Pb(pdc)(bdc)]·2DMF (1, H2bdc = 1,4-benzenedicarboxylic acid and H2pdc = 3,5-pyridinedicarboxylic acid) has been produced via reaction of Pb(NO3)2 with the two organic linkers in a mixed solvent of DMF and water. Complex 1 has high photocatalytic degradation efficiency for methylene blue and rhodamine B under ultraviolet light irradiation. The mechanism of photocatalysis was hypothesized and verified in detail by the r photocatalysis reaction in the existence of the hydroxyl radical scavenger mannitol. Furthermore, the influence of the inflammatory response in the severe burns rats was evaluated. Firstly, the inflammatory response levels were assessed by measuring the content of IL-6 and TNF-α in the plasma after treated with compound. Next, the real time RT-PCR was carried out to determine the signaling pathway of NF-κB relative expression in inflammatory cells.