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 supports the pathophysiological study of myocardial ischemic diseases and provides molecular pathological evidence for forensic discrimination of death causes.展开更多
The key regulators and regeneration-associated genes involved in axonal regeneration of neurons after injury have not been clarified.In high-throughput sequencing,various factors influence the final sequencing results...The key regulators and regeneration-associated genes involved in axonal regeneration of neurons after injury have not been clarified.In high-throughput sequencing,various factors influence the final sequencing results,including the number and size of cells,the depth of sequencing,and the method of cell separation.There is still a lack of research on the detailed molecular expression profile during the regeneration of dorsal root ganglion neuron axon.In this study,we performed lase r-capture microdissection coupled with RNA sequencing on dorsal root ganglion neurons at 0,3,6,and 12 hours and 1,3,and 7 days after sciatic nerve crush in rats.We identified three stages after dorsal root ganglion injury:early(3-12 hours),pre-regeneration(1 day),and regeneration(3-7 days).Gene expression patterns and related function enrichment res ults showed that one module of genes was highly related to axonal regeneration.We verified the up-regulation of activating transcription factor 3(Atf3),Kruppel like factor 6(Klf6),AT-rich inte raction domain 5A(Arid5α),CAMP responsive element modulator(Crem),and FOS like 1,AP-1 transcription factor Subunit(Fosl1) in dorsal root ganglion neurons after injury.Suppressing these transcription factors(Crem,Arid5o,Fosl1 and Klf6) reduced axonal regrowth in vitro.As the hub transcription factor,Atf3 showed higher expression and activity at the preregeneration and regeneration stages.G protein-coupled estrogen receptor 1(Gper1),inte rleukin 12a(Il12α),estrogen receptor 1(ESR1),and interleukin 6(IL6) may be upstream factors that trigger the activation of Atf3 during the repair of axon injury in the early stage.Our study presents the detailed molecular expression profile during axonal regeneration of dorsal root ganglion neurons after peripheral nerve injury.These findings may provide reference for the clinical screening of molecular targets for the treatment of peripheral nerve injury.展开更多
Vascular remodeling is a pathological basis of various disorders. Therefore, it is necessary to understand the occurrence, prevention, and treatment of vascular remodeling. Krüppel-like factor 5 (KLF5) has been i...Vascular remodeling is a pathological basis of various disorders. Therefore, it is necessary to understand the occurrence, prevention, and treatment of vascular remodeling. Krüppel-like factor 5 (KLF5) has been identified as a significant factor in cardiovascular diseases during the last two decades. This review provides a mechanism network of function and regulation of KLF5 in vascular remodeling based on newly published data and gives a summary of its potential therapeutic applications. KLF5 modulates numerous biological processes, which play essential parts in the development of vascular remodeling, such as cell proliferation, phenotype switch, extracellular matrix deposition, inflammation, and angiogenesis by altering downstream genes and signaling pathways. Considering its essential functions, KLF5 could be developed as a potent therapeutic target in vascular disorders.展开更多
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 supports the pathophysiological study of myocardial ischemic diseases and provides molecular pathological evidence for forensic discrimination of death causes.
基金supported by the National Natural Science Foundation of China,Nos. 31730031 and 32130060the National Major Project of Research and Development,No. 2017YFA0104700the Natural Science Foundation of Jiangsu Province,No. BK20202013 (all to XSG)。
文摘The key regulators and regeneration-associated genes involved in axonal regeneration of neurons after injury have not been clarified.In high-throughput sequencing,various factors influence the final sequencing results,including the number and size of cells,the depth of sequencing,and the method of cell separation.There is still a lack of research on the detailed molecular expression profile during the regeneration of dorsal root ganglion neuron axon.In this study,we performed lase r-capture microdissection coupled with RNA sequencing on dorsal root ganglion neurons at 0,3,6,and 12 hours and 1,3,and 7 days after sciatic nerve crush in rats.We identified three stages after dorsal root ganglion injury:early(3-12 hours),pre-regeneration(1 day),and regeneration(3-7 days).Gene expression patterns and related function enrichment res ults showed that one module of genes was highly related to axonal regeneration.We verified the up-regulation of activating transcription factor 3(Atf3),Kruppel like factor 6(Klf6),AT-rich inte raction domain 5A(Arid5α),CAMP responsive element modulator(Crem),and FOS like 1,AP-1 transcription factor Subunit(Fosl1) in dorsal root ganglion neurons after injury.Suppressing these transcription factors(Crem,Arid5o,Fosl1 and Klf6) reduced axonal regrowth in vitro.As the hub transcription factor,Atf3 showed higher expression and activity at the preregeneration and regeneration stages.G protein-coupled estrogen receptor 1(Gper1),inte rleukin 12a(Il12α),estrogen receptor 1(ESR1),and interleukin 6(IL6) may be upstream factors that trigger the activation of Atf3 during the repair of axon injury in the early stage.Our study presents the detailed molecular expression profile during axonal regeneration of dorsal root ganglion neurons after peripheral nerve injury.These findings may provide reference for the clinical screening of molecular targets for the treatment of peripheral nerve injury.
基金The work was supported by the National Natural Science Foundation of China(81970360).
文摘Vascular remodeling is a pathological basis of various disorders. Therefore, it is necessary to understand the occurrence, prevention, and treatment of vascular remodeling. Krüppel-like factor 5 (KLF5) has been identified as a significant factor in cardiovascular diseases during the last two decades. This review provides a mechanism network of function and regulation of KLF5 in vascular remodeling based on newly published data and gives a summary of its potential therapeutic applications. KLF5 modulates numerous biological processes, which play essential parts in the development of vascular remodeling, such as cell proliferation, phenotype switch, extracellular matrix deposition, inflammation, and angiogenesis by altering downstream genes and signaling pathways. Considering its essential functions, KLF5 could be developed as a potent therapeutic target in vascular disorders.
