Diabetic or hyperglycaemic conditions stimulate the inflammatory response, excessive accumulation of extracellular matrix, and result in glomerulosclerosis, a scarring process of diabetic nephropathy. c-Jun activation domain-binding protein 1 (JAB1) functions as a regulator of pathways involved in cellular apoptosis and proliferation. The role of JAB1 in diabetic nephropathy was investigated in this study. Firstly, glomerular mesangial cells (GMCs) were treated with high glucose, and high glucose conditions induced up-regulation of JAB1 in the GMCs. Moreover, IL-6, TNF-α, MCP-1, and IL-1β were also elevated in high glucose-induced GMCs. Secondly, silencing of JAB1 reduced the levels of IL-6, TNF-α, MCP-1, and IL-1β in high glucose-induced GMCs. In addition, silencing of JAB1 attenuated the high glucose-induced decrease of superoxide dismutase (SOD) and the increase of reactive oxygen species (ROS) and malondialdehyde (MDA). The increased TGF-β1, collagen I, collagen IV, and fibronectin levels in high glucose-induced GMCs were restored by knockdown of JAB1. Thirdly, angiopoietin-like protein 2 (ANGPTL2) expression was reduced by JAB1. Over-expression of ANGPTL2 weakened the JAB1 silence-induced decrease of IL-6, TNF-α, MCP-1, IL-1β, TGF-β1, collagen I, collagen IV, and fibronectin. In conclusion, silencing of JAB1 reduced extracellular matrix deposition and suppressed inflammation in high glucose-induced GMCs through down-regulation of ANGPTL2.
- MeSH
- angiopoetinu podobné proteiny metabolismus MeSH
- angiopoetinu podobný protein 2 MeSH
- diabetické nefropatie * metabolismus MeSH
- extracelulární matrix metabolismus MeSH
- fibronektiny metabolismus MeSH
- glukosa metabolismus toxicita MeSH
- interleukin-6 MeSH
- kolagen metabolismus MeSH
- lidé MeSH
- mesangiální buňky * metabolismus MeSH
- signální transdukce MeSH
- TNF-alfa metabolismus MeSH
- transformující růstový faktor beta1 metabolismus MeSH
- zánět MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Circulating miRNAs have been proposed as the effective diagnostic biomarkers for muscular fibrosis-associated diseases. However, circulating biomarkers for early diagnosis of contracture muscles are limited in gluteal muscle contracture (GMC) patients. Here we sought to explore the abnormally expressed miRNAs in plasma and contraction bands of GMC patients. The results showed miR-29a-3p expression in plasma and contraction bands tissue was significantly reduced in GMC patients compared with normal control. Cell viability and levels of proliferation-associated protein cyclin D1 and cyclin-dependent-kinase 2 (CDK2) were powerfully inhibited by miR-29a mimics and enhanced by miR-29a inhibitor compared with negative control. Furthermore, miR-29a mimics effectively impeded, while miR-29a inhibitor enhanced the expression of collagen I and collagen III, followed by the secretion of transforming growth factor beta1 (TGF-beta1), TGF-beta3 and connective tissue growth factor (CTGF) in primary human contraction bands (CB) fibroblasts. The miR-29a-3p negatively regulated the expression of TGF-beta1 through binding to the 3´ UTR region of SERPINH1 (encoding heat shock protein HSP47), but had no effect on Smad2 activity. The miR-29a-3p was inversely correlated with HSP47 in contraction bands tissue from GMC patients. Collectively, miR-29a was notably depressed and regulated cell viability and fibrosis by directly targeting HSP47 in GMC, which suggest that circulating miR-29a might be a potential biomarker for early diagnosis and provides a novel therapeutic target for GMC.
- MeSH
- biologické markery metabolismus MeSH
- dospělí MeSH
- fibroblasty metabolismus patologie MeSH
- fibróza genetika patologie prevence a kontrola MeSH
- hýždě patologie MeSH
- kontraktura genetika patologie prevence a kontrola MeSH
- kultivované buňky MeSH
- lidé MeSH
- mikro RNA genetika MeSH
- proteiny tepelného šoku HSP47 genetika metabolismus MeSH
- studie případů a kontrol MeSH
- svaly metabolismus patologie MeSH
- transformující růstový faktor beta1 genetika metabolismus MeSH
- viabilita buněk fyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The present experiments were performed to study the effects and time trends of different anesthetic agents on the left ventricular (LV) systolic function and heart rate by high-resolution echocardiography in mice. Ten male C57BL/6J mice were submitted to echocardiography imaging separated by 72-hour intervals under the following conditions: 1) conscious mice, 2) mice anesthetized with isoflurane (ISO, inhaled), 3) mice anesthetized with tribromoethanol (TBE, intraperitoneal), 4) mice anesthetized with chloral hydrate (CH, intraperitoneal), and 5) mice anesthetized with pentobarbital sodium (PS, intraperitoneal). The effect of ISO, TBE, CH, and PS on LV systolic function was measured at 0, 1, 2, 3, 4, 6, 8, and 10 min after anesthesia. The results showed that LV systolic function and heart rate (HR) of anesthetized mice were reduced significantly (P<0.05), compared with results in the same mice studied in the conscious state. In addition, the results indicated that the anesthetic with the least effect on LV function was CH, and followed by TBE, PS, ISO. We conclude that different anesthetic agents always depressed the HR and LV systolic function of mice, and, furthermore, the effects and time trends of different anesthetics on LV function are different. In echocardiographic experiments, we should choose proper anesthetic agents according to the experimental requirements.
- MeSH
- anestetika toxicita MeSH
- dysfunkce levé srdeční komory chemicky indukované diagnostické zobrazování patofyziologie MeSH
- echokardiografie účinky léků metody MeSH
- funkce levé komory srdeční účinky léků fyziologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- náhodné rozdělení MeSH
- srdeční frekvence účinky léků fyziologie MeSH
- systola účinky léků fyziologie MeSH
- tepový objem účinky léků fyziologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The major pathobiological mechanisms of IR injury include excitotoxicity, oxidative stress, and inflammation. TF3, a major constituent of black tea, possesses biological functions such as anti-oxidative and anti-inflammatory activities. The purpose of this study was to verify the neuronal protective potential of TF3 and its mechanisms against cerebral IR injury in rats. TF3 administration (10 and 20 mg.kg-1) ameliorated the infarct volume. TF3 also decreased the content of MDA and NO. TF3 significantly increased the activity of SOD and GSH-Px, which were reduced by IR injury. Administration of TF3 decreased mRNA and protein expression of COX-2 and iNOS. DNA binding and Western blotting revealed an increase in NF-?B activation and I?B depletion in IR brain tissue. Pretreatment with TF3 markedly inhibited IRinduced increase in nuclear localization of NF-?B, and preserved I?B in the cytoplasm. The results show that TF3 exerts protective effects against cerebral IR injury by reducing oxidative stress and modulating the NF-?B activation.
- MeSH
- biflavonoidy farmakologie terapeutické užití MeSH
- ischemie mozku MeSH
- katechin farmakologie terapeutické užití MeSH
- krysa rodu rattus MeSH
- kyselina gallová farmakologie terapeutické užití MeSH
- modely u zvířat MeSH
- NF-kappa B farmakokinetika MeSH
- oxidační stres účinky záření MeSH
- reaktivní formy kyslíku farmakokinetika MeSH
- reperfuzní poškození patofyziologie MeSH
- Check Tag
- krysa rodu rattus MeSH
- MeSH
- cyklosporin farmakologie škodlivé účinky terapeutické užití MeSH
- kombinovaná farmakoterapie MeSH
- losartan farmakologie terapeutické užití MeSH
- modely nemocí na zvířatech MeSH
- nemoci ledvin diagnóza farmakoterapie chemicky indukované MeSH
- pravastatin farmakologie terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH
