Non-alcoholic fatty liver disease (NAFLD) has become a global issue and a severe threat to public health.However, to date, no approved therapeutic drugs have been developed. Dietary interventions with naturalproducts ...Non-alcoholic fatty liver disease (NAFLD) has become a global issue and a severe threat to public health.However, to date, no approved therapeutic drugs have been developed. Dietary interventions with naturalproducts have shown promise in preventing and treating NAFLD. Sulforaphane (SFN) is a phytocompoundwith antioxidant and anti-inflammatory properties, and previous research has demonstrated that SFN canameliorate hepatic lipid accumulation and inflammation. However, the molecular mechanisms underlying thesebeneficial effects remain unclear. In this study, we confirmed the protective effects of SFN on excessive lipidaccumulation and inflammatory injury in a high-fat, high-fructose diet-induced non-alcoholic steatohepatitis(NASH) mouse model. We found that SFN attenuates the inflammatory injury in a macrophage cell line andthe liver of NASH mice, owing to the promotion of M1-type macrophage polarization toward the M2-type andthe regulation of inflammatory mediators. Further analysis demonstrated that this SFN-induced macrophageM2-type polarization occurs in a Krüppel-like factor 4 (KLF4)-dependent manner. In summary, we uncovereda new mechanism of action underlying SFN activity and provide evidence that dietary intervention with SFNmight be protective against NASH.展开更多
Salidroside is extensively used as a herbal medicine worldwide, and it has been shown to protect against disruption of endothelial homeostasis and act as an anti-aging agent. The present study aimed to investigate the...Salidroside is extensively used as a herbal medicine worldwide, and it has been shown to protect against disruption of endothelial homeostasis and act as an anti-aging agent. The present study aimed to investigate the ameliorative effects of salidroside on homocysteine (Hcy)-induced cell senescence in human umbilical vein endothelial cells (HUVECs) that were mediated via inhibition of Krüppel-like factor 4 (KLF4). An endothelial cell senescence model was induced by Hcy. The cell viability, activities of telomerase and lactate dehydrogenase (LDH), and the level of reactive oxygen species were determined using commercial kits. The expression levels of KLF4, p53 and p21 were determined via western blot analysis, whereas the mRNA expression levels of KLF4 were detected by reverse transcription-quantitative PCR. Small interfering RNA-mediated knockdown of KLF4 was found to reverse Hcy-induced cell senescence. Hcy treatment led to an accelerated cell senescence, as evidenced by decreases in both cell viability and telomerase activity, whereas increases were noted in the leakage of LDH and the level of reactive oxygen species, in addition to an up-regulation of the protein levels of p53 and p21, and up-regulation of KLF4 at both the mRNA and protein level. Treatment with salidroside ameliorated Hcy-induced cell senescence in a dose-dependent manner. Taken together, these results suggested that Hcy may induce cell senescence through upregulation of KLF4, and this may be reversed by treatment with salidroside. Therefore, salidroside was shown to inhibit Hcy-induced cell senescence through KLF4 inhibition.展开更多
Aim: Colorectal cancer (CRC) is the third leading cancer-related cause of death due to its propensity to metastasize. Epithelial-mesenchymal transition (EMT) is a multistep process important for invasion and metastasi...Aim: Colorectal cancer (CRC) is the third leading cancer-related cause of death due to its propensity to metastasize. Epithelial-mesenchymal transition (EMT) is a multistep process important for invasion and metastasis of CRC. Krüppel-like factor 4 (KLF4) is a zinc finger transcription factor highly expressed in differentiated cells of the intestinal epithelium. KLF4 has been shown to play a tumor suppressor role during CRC tumorigenesis - its loss accelerates development and progression of cancer. The present study examined the relationship between KLF4 and markers of EMT in CRC. Methods: Immunofluorescence staining for KLF4 and EMT markers was performed on archived patient samples after colorectal cancer resection and on colonic tissues of mice with colitis-associated cancer. Results: We found that KLF4 expression is lost in tumor sections obtained from CRC patients and in those of mouse colon following azoxymethane and dextran sodium sulfate (AOM/DSS) treatment when compared to their respective normal appearing mucosa. Importantly, in CRC patient tumor sections, we observed a negative correlation between KLF4 levels and mesenchymal markers including TWIST, β-catenin, claudin-1, N-cadherin, and ;vimentin. Similarly, in tumor tissues from AOM/DSS-treated mice, KLF4 levels were negatively correlated with mesenchymal markers including SNAI2, β-catenin, and vimentin and positively correlated with the epithelial marker E-cadherin. Conclusion: These findings suggest that the loss of KLF4 expression is a potentially significant indicator of EMT in CRC.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
Non-alcoholic fatty liver disease(NAFLD)is a common chronic disease characterized by excessive fat accumulation in hepatocytes in the absence of alcohol consumption.Modern trends towards excessive calorie intake and s...Non-alcoholic fatty liver disease(NAFLD)is a common chronic disease characterized by excessive fat accumulation in hepatocytes in the absence of alcohol consumption.Modern trends towards excessive calorie intake and sedentary life styles have increased the prevalence of NAFLD accompanied by obesity and type 2 diabetes.However,the molecular mechanisms underlying the initiation and progression of NAFLD are not clear.Zinc finger proteins(ZFPs)are a superfamily of metalloproteins that contain zinc finger motifs.ZFPs play diverse physiological roles in tissue homeostasis and also contribute to many pathological conditions,including metabolic,cardiovascular,and neurodegenerative diseases and various types of cancer.In this review,we highlight our current knowledge of several ZFPs that play critical roles in the progression of NAFLD,describe their mechanistic functional networks,and discuss the potential for ZFPs as therapeutic targets for NAFLD.展开更多
基金supported by the Science and Technology project of Henan Province(202102310142)the National Natural Science Foundation of China(32001806)。
文摘Non-alcoholic fatty liver disease (NAFLD) has become a global issue and a severe threat to public health.However, to date, no approved therapeutic drugs have been developed. Dietary interventions with naturalproducts have shown promise in preventing and treating NAFLD. Sulforaphane (SFN) is a phytocompoundwith antioxidant and anti-inflammatory properties, and previous research has demonstrated that SFN canameliorate hepatic lipid accumulation and inflammation. However, the molecular mechanisms underlying thesebeneficial effects remain unclear. In this study, we confirmed the protective effects of SFN on excessive lipidaccumulation and inflammatory injury in a high-fat, high-fructose diet-induced non-alcoholic steatohepatitis(NASH) mouse model. We found that SFN attenuates the inflammatory injury in a macrophage cell line andthe liver of NASH mice, owing to the promotion of M1-type macrophage polarization toward the M2-type andthe regulation of inflammatory mediators. Further analysis demonstrated that this SFN-induced macrophageM2-type polarization occurs in a Krüppel-like factor 4 (KLF4)-dependent manner. In summary, we uncovereda new mechanism of action underlying SFN activity and provide evidence that dietary intervention with SFNmight be protective against NASH.
文摘Salidroside is extensively used as a herbal medicine worldwide, and it has been shown to protect against disruption of endothelial homeostasis and act as an anti-aging agent. The present study aimed to investigate the ameliorative effects of salidroside on homocysteine (Hcy)-induced cell senescence in human umbilical vein endothelial cells (HUVECs) that were mediated via inhibition of Krüppel-like factor 4 (KLF4). An endothelial cell senescence model was induced by Hcy. The cell viability, activities of telomerase and lactate dehydrogenase (LDH), and the level of reactive oxygen species were determined using commercial kits. The expression levels of KLF4, p53 and p21 were determined via western blot analysis, whereas the mRNA expression levels of KLF4 were detected by reverse transcription-quantitative PCR. Small interfering RNA-mediated knockdown of KLF4 was found to reverse Hcy-induced cell senescence. Hcy treatment led to an accelerated cell senescence, as evidenced by decreases in both cell viability and telomerase activity, whereas increases were noted in the leakage of LDH and the level of reactive oxygen species, in addition to an up-regulation of the protein levels of p53 and p21, and up-regulation of KLF4 at both the mRNA and protein level. Treatment with salidroside ameliorated Hcy-induced cell senescence in a dose-dependent manner. Taken together, these results suggested that Hcy may induce cell senescence through upregulation of KLF4, and this may be reversed by treatment with salidroside. Therefore, salidroside was shown to inhibit Hcy-induced cell senescence through KLF4 inhibition.
基金grants from the National Institutes of Health awarded to Yang VW (CA084197)
文摘Aim: Colorectal cancer (CRC) is the third leading cancer-related cause of death due to its propensity to metastasize. Epithelial-mesenchymal transition (EMT) is a multistep process important for invasion and metastasis of CRC. Krüppel-like factor 4 (KLF4) is a zinc finger transcription factor highly expressed in differentiated cells of the intestinal epithelium. KLF4 has been shown to play a tumor suppressor role during CRC tumorigenesis - its loss accelerates development and progression of cancer. The present study examined the relationship between KLF4 and markers of EMT in CRC. Methods: Immunofluorescence staining for KLF4 and EMT markers was performed on archived patient samples after colorectal cancer resection and on colonic tissues of mice with colitis-associated cancer. Results: We found that KLF4 expression is lost in tumor sections obtained from CRC patients and in those of mouse colon following azoxymethane and dextran sodium sulfate (AOM/DSS) treatment when compared to their respective normal appearing mucosa. Importantly, in CRC patient tumor sections, we observed a negative correlation between KLF4 levels and mesenchymal markers including TWIST, β-catenin, claudin-1, N-cadherin, and ;vimentin. Similarly, in tumor tissues from AOM/DSS-treated mice, KLF4 levels were negatively correlated with mesenchymal markers including SNAI2, β-catenin, and vimentin and positively correlated with the epithelial marker E-cadherin. Conclusion: These findings suggest that the loss of KLF4 expression is a potentially significant indicator of EMT in CRC.
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.
基金This work was supported by funds from the National Natural Science Foundation of China(31770840 to X.Ma and 31800989 to L.Xu)the Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learning(TP2017042 to X.Ma)。
文摘Non-alcoholic fatty liver disease(NAFLD)is a common chronic disease characterized by excessive fat accumulation in hepatocytes in the absence of alcohol consumption.Modern trends towards excessive calorie intake and sedentary life styles have increased the prevalence of NAFLD accompanied by obesity and type 2 diabetes.However,the molecular mechanisms underlying the initiation and progression of NAFLD are not clear.Zinc finger proteins(ZFPs)are a superfamily of metalloproteins that contain zinc finger motifs.ZFPs play diverse physiological roles in tissue homeostasis and also contribute to many pathological conditions,including metabolic,cardiovascular,and neurodegenerative diseases and various types of cancer.In this review,we highlight our current knowledge of several ZFPs that play critical roles in the progression of NAFLD,describe their mechanistic functional networks,and discuss the potential for ZFPs as therapeutic targets for NAFLD.
