Chronic inflammation plays a pivotal role in insulin resistance and type 2 diabetes,yet the mechanisms are not completely understood.Here,we demonstrated that serum LPS levels were significantly higher in newly diagno...Chronic inflammation plays a pivotal role in insulin resistance and type 2 diabetes,yet the mechanisms are not completely understood.Here,we demonstrated that serum LPS levels were significantly higher in newly diagnosed diabetic patients than in normal control.miR-145 level in peripheral blood mononuclear cells decreased in type 2 diabetics.LPS repressed the transcription of miR-143/145 cluster and decreased miR-145 levels.Attenuation of miR-145 activity by anti-miR-145 triggered liver inflammation and increased serum chemokines in C57BL/6 J mice.Conversely,lentivirus-mediated miR-145 overexpression inhibited macrophage infiltration,reduced body weight,and improved glucose metabolism in db/db mice.And miR-145 overexpression markedly reduced plaque size in the aorta in ApoE−/−mice.Both OPG and KLF5 were targets of miR-145.miR-145 repressed cell proliferation and induced apoptosis partially by targeting OPG and KLF5.miR-145 also suppressed NF-κB activation by targeting OPG and KLF5.Our findings provide an association of the environment with the progress of metabolic disorders.Increasing miR-145 may be a new potential therapeutic strategy in preventing and treating metabolic diseases such as type 2 diabetes and atherosclerosis.展开更多
Background:Accumulated studies have demonstrated that Kruppel‑like factor 5(KLF5),a transcription factor,plays an important role in regulating cell proliferation and tissue remodeling through the expression of its dow...Background:Accumulated studies have demonstrated that Kruppel‑like factor 5(KLF5),a transcription factor,plays an important role in regulating cell proliferation and tissue remodeling through the expression of its downstream genes.KLF5‑related factors are expected to be involved in the healing process after myocardial injury or myocardial ischemic changes,especially for the forensic diagnosis of myocardial ischemic physiopathology.Aim and Objectives:This study aimed to explore the discrimination ability and applicability of KLF5-related factors in SCD caused by MI compared with other causes of death to provide further insights into the forensic diagnosis of myocardial ischemic pathology.Materials and Methods:The relative quantification of F‑Box and WD Repeat Domain Containing 7(FBW7),KLF5,factor‑binding protein(FGFBP)1,and FGFBP2 messenger RNAs(mRNAs)in myocardial tissue samples was performed using real‑time fluorescence quantitative reverse transcription polymerase chain reaction.KLF5 and FGFBP1/2 protein levels were examined using immunohistochemistry(IHC).The forensic autopsy cases(27 in total,autopsy within 72 h postmortem)included seven cases of acute myocardial infarction and 10 cases of acute myocardial ischemia.There were 10 cases in the control group,including four cases of traffic injury one case of injury by fall from height,one case of electric death,and four cases of blunt force injury.Results:Characteristic results were found in myocardial samples from three groups of deaths:KLF5 and FGFBP1 mRNA levels were significantly elevated in the infarction and ischemia groups,while FBW7 mRNA levels were significantly decreased.FBW7 is an important ubiquitin ligase that can mediate the degradation of KLF5 protein.In addition,FBW7 and FGFBP2 mRNA levels were decreased in the infarction group compared with the ischemia group.The IHC results were consistent with the observed mRNA expression patterns.Conclusions:Quantitative detection of FBW7,KLF5,FGFBP1,and FGFBP2 mRNA transcripts in myocardial tissues展开更多
基金This work was supported by grants from the National Natural Science Foundation of China(81270902,81381220308,and 30230380).
文摘Chronic inflammation plays a pivotal role in insulin resistance and type 2 diabetes,yet the mechanisms are not completely understood.Here,we demonstrated that serum LPS levels were significantly higher in newly diagnosed diabetic patients than in normal control.miR-145 level in peripheral blood mononuclear cells decreased in type 2 diabetics.LPS repressed the transcription of miR-143/145 cluster and decreased miR-145 levels.Attenuation of miR-145 activity by anti-miR-145 triggered liver inflammation and increased serum chemokines in C57BL/6 J mice.Conversely,lentivirus-mediated miR-145 overexpression inhibited macrophage infiltration,reduced body weight,and improved glucose metabolism in db/db mice.And miR-145 overexpression markedly reduced plaque size in the aorta in ApoE−/−mice.Both OPG and KLF5 were targets of miR-145.miR-145 repressed cell proliferation and induced apoptosis partially by targeting OPG and KLF5.miR-145 also suppressed NF-κB activation by targeting OPG and KLF5.Our findings provide an association of the environment with the progress of metabolic disorders.Increasing miR-145 may be a new potential therapeutic strategy in preventing and treating metabolic diseases such as type 2 diabetes and atherosclerosis.
基金supported by the Beijing Natural Science Foundation(grant number 7192121,China)General Program of National Natural Science Foundation of China(grant number 81971796,China).
文摘Background:Accumulated studies have demonstrated that Kruppel‑like factor 5(KLF5),a transcription factor,plays an important role in regulating cell proliferation and tissue remodeling through the expression of its downstream genes.KLF5‑related factors are expected to be involved in the healing process after myocardial injury or myocardial ischemic changes,especially for the forensic diagnosis of myocardial ischemic physiopathology.Aim and Objectives:This study aimed to explore the discrimination ability and applicability of KLF5-related factors in SCD caused by MI compared with other causes of death to provide further insights into the forensic diagnosis of myocardial ischemic pathology.Materials and Methods:The relative quantification of F‑Box and WD Repeat Domain Containing 7(FBW7),KLF5,factor‑binding protein(FGFBP)1,and FGFBP2 messenger RNAs(mRNAs)in myocardial tissue samples was performed using real‑time fluorescence quantitative reverse transcription polymerase chain reaction.KLF5 and FGFBP1/2 protein levels were examined using immunohistochemistry(IHC).The forensic autopsy cases(27 in total,autopsy within 72 h postmortem)included seven cases of acute myocardial infarction and 10 cases of acute myocardial ischemia.There were 10 cases in the control group,including four cases of traffic injury one case of injury by fall from height,one case of electric death,and four cases of blunt force injury.Results:Characteristic results were found in myocardial samples from three groups of deaths:KLF5 and FGFBP1 mRNA levels were significantly elevated in the infarction and ischemia groups,while FBW7 mRNA levels were significantly decreased.FBW7 is an important ubiquitin ligase that can mediate the degradation of KLF5 protein.In addition,FBW7 and FGFBP2 mRNA levels were decreased in the infarction group compared with the ischemia group.The IHC results were consistent with the observed mRNA expression patterns.Conclusions:Quantitative detection of FBW7,KLF5,FGFBP1,and FGFBP2 mRNA transcripts in myocardial tissues
