MYB类转录因子GGS1(glucose and GA signaling 1)既受到DELLA蛋白的调控,又与糖受体蛋白HXK1形成核内复合体.前人的这些研究结果暗示,GGS1可能同时参与了赤霉素和糖的信号调控.为了进一步证实GGS1基因在两信号途径中发挥的作用,我们对...MYB类转录因子GGS1(glucose and GA signaling 1)既受到DELLA蛋白的调控,又与糖受体蛋白HXK1形成核内复合体.前人的这些研究结果暗示,GGS1可能同时参与了赤霉素和糖的信号调控.为了进一步证实GGS1基因在两信号途径中发挥的作用,我们对以下两个方面进行了研究.首先对GGS1基因表达谱进行分析,结果表明,GGS1特异在拟南芥各器官的维管组织的韧皮部细胞中表达;用赤霉素和高浓度蔗糖处理能抑制GGS1基因的表达.GGS1同源基因虽和GGS1具有相似的表达谱,但是其表达却不受GA和糖处理的影响,暗示二者间不存在功能冗余.其次,我们获得GGS1过表达转基因植株并通过Q-PCR分析这一植株中GA和糖代谢途径中一些重要相关基因表达变化.结果表明,在GGS1过表达植株中参与GA合成的基因表达升高,GA分解代谢基因表达降低;与糖信号密切相关的光合作用相关基因表达升高.两方面研究结果证实了GGS1的双元功能,即既可以作为GA信号调控的负调控因子,又在糖的信号传递中发挥作用.展开更多
Objective To investigate the effect of Zuogui Jiangtang Jieyu Formula(左归降糖解郁方,ZJJF)on hippocampal neuron apoptosis in diabetic rats with depression and to ascertain whether its mechanism involves the regulation...Objective To investigate the effect of Zuogui Jiangtang Jieyu Formula(左归降糖解郁方,ZJJF)on hippocampal neuron apoptosis in diabetic rats with depression and to ascertain whether its mechanism involves the regulation of JNK signaling pathway.Methods(i)A total of 72 specific pathogen-free(SPF)grade male Sprague Dawley(SD)rats were randomly divided into six groups,with 12 rats in each group:control,model,metformin(Met,0.18 g/kg)+fluoxetine(Flu,1.8 mg/kg),and the high-,medium-,and low-ZJJF dosages(ZJJF-H,20.52 g/kg;ZJJF-M,10.26 g/kg;ZJJF-L,5.13 g/kg)groups.All groups except control group were injected once via the tail vein with streptozotocin(STZ,38 mg/kg)combined with 28 d of chronic unpredictable mild stress(CUMS)to establish diabetic rat models with depression.During the CUMS modeling period,treatments were administered via gavage,with control and model groups receiving an equivalent volume of distilled water for 28 d.The efficacy of ZJJF in reducing blood sugar and alleviating depression was evaluated by measuring fasting blood glucose,insulin,and glycated hemoglobin levels,along with behavioral assessments,including the open field test(OFT),forced swim test(FST),and sucrose preference test(SPT).Hippocampal tissue damage and neuronal apoptosis were evaluated using hematoxylin-eosin(HE)staining and terminal deoxynucleotidyl transferase-mediated dUTP nickend labeling(TUNEL)staining.Apoptosis-related proteins Bax,Bcl-2,caspase-3,and the expression levels of JNK/Elk-1/c-fos signaling pathway were detected using Western blot and real-time quantitative polymerase chain reaction(RT-qPCR).(ii)To further elucidate the role of JNK signaling pathway in hippocampal neuronal apoptosis and the pharmacological effects of ZJJF,an additional 50 SPF grade male SD rats were randomly divided into five groups,with 10 rats in each group:control,model,SP600125(SP6,a JNK antagonist,10 mg/kg),ZJJF(20.52 g/kg),and ZJJF(20.52 g/kg)+Anisomycin(Aniso,a JNK agonist,15 mg/kg)groups.Except for control group,all groups were established as diabetic rat models with depression,and treatments were administered via gavage for ZJJF and intraperitoneal injection for SP6 and Aniso for 28 d during the CUMS modeling period.Behavioral changes in rats were evaluated through the OFT,FST,and SPT,and hippocampal neuron damage and apoptosis were observed using HE staining,Nissl staining,TUNEL staining,and transmission electron microscopy(TEM).Changes in apoptosis-related proteins and JNK signaling pathway in the hippocampal tissues of rats were also analyzed.展开更多
Land animals as well as all organisms in ocean synthesize sulfated polysaccharides. Fungi split from animals about 1.5 billion years ago. As fungi make the evolutionary journey from ocean to land, the biggest changes ...Land animals as well as all organisms in ocean synthesize sulfated polysaccharides. Fungi split from animals about 1.5 billion years ago. As fungi make the evolutionary journey from ocean to land, the biggest changes in their living environment may be a sharp decrease in salt concentration. It is established that sulfated polysaccharides interact with hundreds of signaling molecules and facilitate many signaling transduction pathways, including fibroblast growth factor （FGF） and FGF receptor signaling pathway. The disappearance of sulfated polysaccharides in fimgi and plants on land might indicate that polysaccharides without sulfation might be sufficient in facilitating protein ligand/receptor interactions in low salinity land. Recently, it was reported that plants on land start to synthesize sulfated polysaccharides in high salt environment, suggesting that fungi might be able to do the same when ex- posed in such environment. Interestingly, Cordyceps, a fungus habituating inside caterpillar body, is the most valued traditional Chi- nese Medicine. One of the important pharmaceutical active ingredients in Cordyceps is polysaccharides. Therefore, we hypothesize that the salty environment inside caterpillar body might allow the fungi to synthesize sulfated polysaccharides. To test the hypothesis, we isolated polysaccharides from both lava and sporophore of wild Cordyceps and also from Cordyceps militaris cultured without or with added salts. We then measured the polysaccharide activity using a FGF2/FGFRlc signaling-dependent BaF3 cell proliferation assay and found that polysaccharides isolated from wild Cordyceps activated FGF2/FGFR signaling, indicating that the polysaccha- rides synthesized by wild Cordyceps are indeed different from those by the cultured mycelium.展开更多
Nephrin is a key molecule in podocytes to maintain normal slit diaphragm structure. Nephin interacts with many other podo- cyte and slit diaphragm protein and also mediates important cell signaling pathways in podocyt...Nephrin is a key molecule in podocytes to maintain normal slit diaphragm structure. Nephin interacts with many other podo- cyte and slit diaphragm protein and also mediates important cell signaling pathways in podocytes. Loss of nephrin during the development leads to the congenital nephrotic syndrome in children. Reduction of nephrin expression is often observed in adult kidney diseases including diabetic nephropathy and HIV-associated nephropathy. The critical role of nephrin has been confirmed by different animal models with nepbrin knockout and knockdown. Recent studies demonstrate that knockdown of nephrin expression in adult mice aggravates the progression of＇ unilateral nephrectomy and Adriamycin-induced kidney disease In addition to its critical role in maintaining normal glomerular filtration unit in the kidney, nephrin is also expressed in other organs. However, the exact role of nephrin in kidney and extra-renal organs has not been well characterized. Future studies are required to determine whether nephrin could be developed as a drug target to treat patients with kidney disease.展开更多
Insulin resistance and dysregulated lipid meta- bolism are major causes of type 2 diabetes. Insulin and inflam- matory signal pathways play key roles in insulin resistance and fat accumulation. Specifically, adapter p...Insulin resistance and dysregulated lipid meta- bolism are major causes of type 2 diabetes. Insulin and inflam- matory signal pathways play key roles in insulin resistance and fat accumulation. Specifically, adapter proteins transduce sig- nals from insulin or cytokine receptors to the downstream pathways and may contribute to insulin resistance and disor- dered lipid metabolism in obesity and type 2 diabetes. Here, the recent advances in understanding the roles of adapter proteins in insulin resistance and lipid homeostasis are discussed.展开更多
Objective: To reveal the mechanism of Zuogui Pill (左归丸) in treatment of glucocorticoid-induced osteoporosis from the angle of the Wnt signal transduction pathway and to provide further experimental evidence for exp...Objective: To reveal the mechanism of Zuogui Pill (左归丸) in treatment of glucocorticoid-induced osteoporosis from the angle of the Wnt signal transduction pathway and to provide further experimental evidence for expounding the scientific connotation of "the kidney dominating the bones" in TCM. Methods: Forty-two male Wistar rats were selected and randomly divided into three groups, control group (n=12), model group (n=15) and Zuogui Pill group (n=15). Form the beginning, The rats were injected dexamethasone for eight weeks to make the model of osteoporosis, and the Zuogui Pill were administered intragastrically to the rats of Zuogui Pill group for eight weeks. The relative morphological parameters were measured in the undecalcified tibial slices. And the protein expression levels of Wnt1, LRP-5 and β-catenin in rat tibial osteoblasts (OB) and bone marrow stromal cells (BMC) were detected by immunohistochemistry. Results: Compared with the control group, TBV% and TFS% decreased significantly, while TRS% increased significantly, and the protein expression of Wnt1, LRP-5 and β-catenin in OB and BMC decreased significantly in the model group. And compared with the model group, TBV% and TFS% increased significantly, and expression levels of Wnt1, LRP-5 and β-catenin proteins increased significantly in the Zuogui pill group. Conclusion: Zuogui Pill can prevent and treat glucocorticoid-induced osteoporosis in rats by up-regulating the expression of the key signal molecules Wnt1, LRP-5 and β-catenin in Wnt signal transduction pathway.展开更多
The covalent attachment of O-linked β-N- acetylglucosamine （O-GIcNAc） to Ser/Thr residues of proteins acts as not only a posttranslational modification but also a nutritional sensor in nucleus and cytoplasm, which ...The covalent attachment of O-linked β-N- acetylglucosamine （O-GIcNAc） to Ser/Thr residues of proteins acts as not only a posttranslational modification but also a nutritional sensor in nucleus and cytoplasm, which directly regulates the expression of genes and multiple crucial signal transduction pathways. Dynamic O- GlcNAcylation at Ser/Thr residues is catalyzed by two key enzymes, O-GIcNAc transferase （OGT） and O-GlcNAcase, which are responsible for addition and removal of the O- GlcNAc modification, respectively. O-GlcNAc modifica- tion plays important roles in cellular signaling in animals, especially in human diseases. Two orthologs of OGT in plants, SECRET AGENT and SPINDLY, have been reported to be involved in diverse plant processes. However, compared with the functional mechanisms revealed in animals, the consequences of protein O-GlcNAc modifi- cation in plants is largely unknown, and the relationship between O-GlcNAcylation and cellular processes needs to be explored. In this review, we summarized the recent advances on O-GlcNAc modification and its biological functions in animals and plants, and prospect of more special functions of O-GlcNAc will be revealed in plants.展开更多
Disulfide-bond A oxidoreductase-like protein(DsbA-L)is a molecular chaperone involved in the multimeri-zation of adiponectin.Recent studies have found that DsbA-L is related to metabolic diseases including gestational...Disulfide-bond A oxidoreductase-like protein(DsbA-L)is a molecular chaperone involved in the multimeri-zation of adiponectin.Recent studies have found that DsbA-L is related to metabolic diseases including gestational diabetes mellitus(GDM),and can be regulated by peroxisome proliferator-activated receptorγ(PPARγ)agonists;the specific mechanism,however,is uncertain.Furthermore,the relationship between DsbA-L and the novel adipokine chemerin is also unclear.This article aims to investigate the role of DsbA-L in the improvement of insulin resistance by PPARγagonists in trophoblast cells cultured by the high-glucose simulation of GDM placenta.Immunohistochemistry and western blot were used to detect differences between GDM patients and normal pregnant women in DsbA-L expression in the adipose tissue.The western blot technique was performed to verify the relationship between PPARγagonists and DsbA-L,and to explore changes in key molecules of the insulin signaling pathway,as well as the effect of chemerin on DsbA-L.Results showed that DsbA-L was significantly downregulated in the adipose tissue of GDM patients.Both PPARγagonists and chemerin could upregulate the level of DsbA-L.Silencing DsbA-L affected the function of rosiglitazone to promote the phosphatidylinositol 3-kinase(PI3K)-protein kinase B(PKB)/AKT pathway.Therefore,it is plausible to speculate that DsbA-L is essential in the environment of PPARγagonists for raising insulin sensitivity.Overall,we further clarified the mechanism by which PPARγagonists improve insulin resistance.展开更多
OBJECTIVE: To investigate the protective effects and underlying mechanism of Qingdu decoction(QDD) on experimental rats with severe liver injury induced by thioacetamide(TAA).METHODS: A total of 40 Wistar rats were ra...OBJECTIVE: To investigate the protective effects and underlying mechanism of Qingdu decoction(QDD) on experimental rats with severe liver injury induced by thioacetamide(TAA).METHODS: A total of 40 Wistar rats were randomly divided into normal group(n = 10) and experimental group(n = 30). Rats were administrated the same content of saline in normal group. The rats inthe experimental group were pretreated with TAA at dose of 12 mg/kg lasting 8 weeks, and from 9th week to 12 th week, with TAA at concentration of 36mg/kg. During the 9th week to 12 th week period,the rats were randomly divided into three subgroups(n = 10 each) simultaneously based on the treatment categories: model group, lactulose(LA,3.5 m L/kg) group and QDD(5.95 g/kg) group, orally once per day respectively. At the 12 th week, the content of serum alanine transaminase(ALT), aspartate transaminase(AST), total bilirubin(TBIL), endotoxin(ET) and tumor necrosis factor α(TNF-α) was detected by automatic biochemical analyzer. The plasma prothrombin time(PT), prothrombin time-international normalized ratio(PTR) and prothrombin time activity(PTA) were measured by automatic coagulation analyzer. The level of lipopolysaccharide(LPS)-binding protein(LBP), cluster differentiation 14(CD14) and Toll-like receptor 4(TLR4) expressions was measured by both western blot(WB) and real-time polymerase chain reaction(real-time PCR).RESULTS: Compared with the model group, hepatic morphology in the QDD group was improved under light microscope and transmission electron microscope; at the same time, the contents of serum ALT, AST, TBIL, ET and TNF-α, and level of LBP, CD14 and TLR4 expressions in liver tissues were significantly decreased compared with the model group(P < 0.05), while PTA in the QDD group was enhanced(P < 0.05).CONCLUSION: QDD has the functional effect on improving the injured liver through inhibiting the LPS/TLR4 signaling pathway thus decreasing the level of the inflammatory medicators.展开更多
文摘MYB类转录因子GGS1(glucose and GA signaling 1)既受到DELLA蛋白的调控,又与糖受体蛋白HXK1形成核内复合体.前人的这些研究结果暗示,GGS1可能同时参与了赤霉素和糖的信号调控.为了进一步证实GGS1基因在两信号途径中发挥的作用,我们对以下两个方面进行了研究.首先对GGS1基因表达谱进行分析,结果表明,GGS1特异在拟南芥各器官的维管组织的韧皮部细胞中表达;用赤霉素和高浓度蔗糖处理能抑制GGS1基因的表达.GGS1同源基因虽和GGS1具有相似的表达谱,但是其表达却不受GA和糖处理的影响,暗示二者间不存在功能冗余.其次,我们获得GGS1过表达转基因植株并通过Q-PCR分析这一植株中GA和糖代谢途径中一些重要相关基因表达变化.结果表明,在GGS1过表达植株中参与GA合成的基因表达升高,GA分解代谢基因表达降低;与糖信号密切相关的光合作用相关基因表达升高.两方面研究结果证实了GGS1的双元功能,即既可以作为GA信号调控的负调控因子,又在糖的信号传递中发挥作用.
基金National Natural Science Foundation of China(82104836 and 82104793)Science and Technology Talent Promotion Project of Hunan Province(2023TJ-N22).
文摘Objective To investigate the effect of Zuogui Jiangtang Jieyu Formula(左归降糖解郁方,ZJJF)on hippocampal neuron apoptosis in diabetic rats with depression and to ascertain whether its mechanism involves the regulation of JNK signaling pathway.Methods(i)A total of 72 specific pathogen-free(SPF)grade male Sprague Dawley(SD)rats were randomly divided into six groups,with 12 rats in each group:control,model,metformin(Met,0.18 g/kg)+fluoxetine(Flu,1.8 mg/kg),and the high-,medium-,and low-ZJJF dosages(ZJJF-H,20.52 g/kg;ZJJF-M,10.26 g/kg;ZJJF-L,5.13 g/kg)groups.All groups except control group were injected once via the tail vein with streptozotocin(STZ,38 mg/kg)combined with 28 d of chronic unpredictable mild stress(CUMS)to establish diabetic rat models with depression.During the CUMS modeling period,treatments were administered via gavage,with control and model groups receiving an equivalent volume of distilled water for 28 d.The efficacy of ZJJF in reducing blood sugar and alleviating depression was evaluated by measuring fasting blood glucose,insulin,and glycated hemoglobin levels,along with behavioral assessments,including the open field test(OFT),forced swim test(FST),and sucrose preference test(SPT).Hippocampal tissue damage and neuronal apoptosis were evaluated using hematoxylin-eosin(HE)staining and terminal deoxynucleotidyl transferase-mediated dUTP nickend labeling(TUNEL)staining.Apoptosis-related proteins Bax,Bcl-2,caspase-3,and the expression levels of JNK/Elk-1/c-fos signaling pathway were detected using Western blot and real-time quantitative polymerase chain reaction(RT-qPCR).(ii)To further elucidate the role of JNK signaling pathway in hippocampal neuronal apoptosis and the pharmacological effects of ZJJF,an additional 50 SPF grade male SD rats were randomly divided into five groups,with 10 rats in each group:control,model,SP600125(SP6,a JNK antagonist,10 mg/kg),ZJJF(20.52 g/kg),and ZJJF(20.52 g/kg)+Anisomycin(Aniso,a JNK agonist,15 mg/kg)groups.Except for control group,all groups were established as diabetic rat models with depression,and treatments were administered via gavage for ZJJF and intraperitoneal injection for SP6 and Aniso for 28 d during the CUMS modeling period.Behavioral changes in rats were evaluated through the OFT,FST,and SPT,and hippocampal neuron damage and apoptosis were observed using HE staining,Nissl staining,TUNEL staining,and transmission electron microscopy(TEM).Changes in apoptosis-related proteins and JNK signaling pathway in the hippocampal tissues of rats were also analyzed.
基金supported by the National Natural Science Foundation of China (Grant No. 91129706)
文摘Land animals as well as all organisms in ocean synthesize sulfated polysaccharides. Fungi split from animals about 1.5 billion years ago. As fungi make the evolutionary journey from ocean to land, the biggest changes in their living environment may be a sharp decrease in salt concentration. It is established that sulfated polysaccharides interact with hundreds of signaling molecules and facilitate many signaling transduction pathways, including fibroblast growth factor （FGF） and FGF receptor signaling pathway. The disappearance of sulfated polysaccharides in fimgi and plants on land might indicate that polysaccharides without sulfation might be sufficient in facilitating protein ligand/receptor interactions in low salinity land. Recently, it was reported that plants on land start to synthesize sulfated polysaccharides in high salt environment, suggesting that fungi might be able to do the same when ex- posed in such environment. Interestingly, Cordyceps, a fungus habituating inside caterpillar body, is the most valued traditional Chi- nese Medicine. One of the important pharmaceutical active ingredients in Cordyceps is polysaccharides. Therefore, we hypothesize that the salty environment inside caterpillar body might allow the fungi to synthesize sulfated polysaccharides. To test the hypothesis, we isolated polysaccharides from both lava and sporophore of wild Cordyceps and also from Cordyceps militaris cultured without or with added salts. We then measured the polysaccharide activity using a FGF2/FGFRlc signaling-dependent BaF3 cell proliferation assay and found that polysaccharides isolated from wild Cordyceps activated FGF2/FGFR signaling, indicating that the polysaccha- rides synthesized by wild Cordyceps are indeed different from those by the cultured mycelium.
文摘Nephrin is a key molecule in podocytes to maintain normal slit diaphragm structure. Nephin interacts with many other podo- cyte and slit diaphragm protein and also mediates important cell signaling pathways in podocytes. Loss of nephrin during the development leads to the congenital nephrotic syndrome in children. Reduction of nephrin expression is often observed in adult kidney diseases including diabetic nephropathy and HIV-associated nephropathy. The critical role of nephrin has been confirmed by different animal models with nepbrin knockout and knockdown. Recent studies demonstrate that knockdown of nephrin expression in adult mice aggravates the progression of＇ unilateral nephrectomy and Adriamycin-induced kidney disease In addition to its critical role in maintaining normal glomerular filtration unit in the kidney, nephrin is also expressed in other organs. However, the exact role of nephrin in kidney and extra-renal organs has not been well characterized. Future studies are required to determine whether nephrin could be developed as a drug target to treat patients with kidney disease.
基金Acknowledgements This work was supported by the Changbai Mountain Scholars Program of Jilin Province 2013046 （to Z. C.）, the Jilin Talent Development Foundation 111860000 （to Z. C.）, the National Natural Science Foundation of China Grant 31500957 （to Z. C.）, and the startup funds from Northeast Normal University 120401204 （to Z. C.）. I thank Dr. Mark J. Canet （University of Michigan） for editing this manuscript. I also thank lab members （Xinzhi Li, Wangshu Qin, Linna Jia, Sha Li, Xiaomeng Ren, Xue Dong, and Jiana Liu） at Northeast Normal University for helpful discussion. I apologize to colleagues whose relevant work could not be cited here due to space limitation.
文摘Insulin resistance and dysregulated lipid meta- bolism are major causes of type 2 diabetes. Insulin and inflam- matory signal pathways play key roles in insulin resistance and fat accumulation. Specifically, adapter proteins transduce sig- nals from insulin or cytokine receptors to the downstream pathways and may contribute to insulin resistance and disor- dered lipid metabolism in obesity and type 2 diabetes. Here, the recent advances in understanding the roles of adapter proteins in insulin resistance and lipid homeostasis are discussed.
基金supported by a grant from National Natural Science Foundation of China (NO.30873210)
文摘Objective: To reveal the mechanism of Zuogui Pill (左归丸) in treatment of glucocorticoid-induced osteoporosis from the angle of the Wnt signal transduction pathway and to provide further experimental evidence for expounding the scientific connotation of "the kidney dominating the bones" in TCM. Methods: Forty-two male Wistar rats were selected and randomly divided into three groups, control group (n=12), model group (n=15) and Zuogui Pill group (n=15). Form the beginning, The rats were injected dexamethasone for eight weeks to make the model of osteoporosis, and the Zuogui Pill were administered intragastrically to the rats of Zuogui Pill group for eight weeks. The relative morphological parameters were measured in the undecalcified tibial slices. And the protein expression levels of Wnt1, LRP-5 and β-catenin in rat tibial osteoblasts (OB) and bone marrow stromal cells (BMC) were detected by immunohistochemistry. Results: Compared with the control group, TBV% and TFS% decreased significantly, while TRS% increased significantly, and the protein expression of Wnt1, LRP-5 and β-catenin in OB and BMC decreased significantly in the model group. And compared with the model group, TBV% and TFS% increased significantly, and expression levels of Wnt1, LRP-5 and β-catenin proteins increased significantly in the Zuogui pill group. Conclusion: Zuogui Pill can prevent and treat glucocorticoid-induced osteoporosis in rats by up-regulating the expression of the key signal molecules Wnt1, LRP-5 and β-catenin in Wnt signal transduction pathway.
基金This work was supported by the National Basic Research Program of China （2011CB915404） the National Natural Science Foundation of China （No.31270310） and the Fundamental Research Funds for the Central Universities （2572014EA04）.
文摘The covalent attachment of O-linked β-N- acetylglucosamine （O-GIcNAc） to Ser/Thr residues of proteins acts as not only a posttranslational modification but also a nutritional sensor in nucleus and cytoplasm, which directly regulates the expression of genes and multiple crucial signal transduction pathways. Dynamic O- GlcNAcylation at Ser/Thr residues is catalyzed by two key enzymes, O-GIcNAc transferase （OGT） and O-GlcNAcase, which are responsible for addition and removal of the O- GlcNAc modification, respectively. O-GlcNAc modifica- tion plays important roles in cellular signaling in animals, especially in human diseases. Two orthologs of OGT in plants, SECRET AGENT and SPINDLY, have been reported to be involved in diverse plant processes. However, compared with the functional mechanisms revealed in animals, the consequences of protein O-GlcNAc modifi- cation in plants is largely unknown, and the relationship between O-GlcNAcylation and cellular processes needs to be explored. In this review, we summarized the recent advances on O-GlcNAc modification and its biological functions in animals and plants, and prospect of more special functions of O-GlcNAc will be revealed in plants.
基金Project supported by the National Key Research and Development Program of China(Nos.2016YFC1000405 , 2018YFC1002903)。
文摘Disulfide-bond A oxidoreductase-like protein(DsbA-L)is a molecular chaperone involved in the multimeri-zation of adiponectin.Recent studies have found that DsbA-L is related to metabolic diseases including gestational diabetes mellitus(GDM),and can be regulated by peroxisome proliferator-activated receptorγ(PPARγ)agonists;the specific mechanism,however,is uncertain.Furthermore,the relationship between DsbA-L and the novel adipokine chemerin is also unclear.This article aims to investigate the role of DsbA-L in the improvement of insulin resistance by PPARγagonists in trophoblast cells cultured by the high-glucose simulation of GDM placenta.Immunohistochemistry and western blot were used to detect differences between GDM patients and normal pregnant women in DsbA-L expression in the adipose tissue.The western blot technique was performed to verify the relationship between PPARγagonists and DsbA-L,and to explore changes in key molecules of the insulin signaling pathway,as well as the effect of chemerin on DsbA-L.Results showed that DsbA-L was significantly downregulated in the adipose tissue of GDM patients.Both PPARγagonists and chemerin could upregulate the level of DsbA-L.Silencing DsbA-L affected the function of rosiglitazone to promote the phosphatidylinositol 3-kinase(PI3K)-protein kinase B(PKB)/AKT pathway.Therefore,it is plausible to speculate that DsbA-L is essential in the environment of PPARγagonists for raising insulin sensitivity.Overall,we further clarified the mechanism by which PPARγagonists improve insulin resistance.
基金Supported by Beijing Natural Science Foundation of China(Investigation of the Mechanism on Qingdu Decoction in Repairing Injured Liver with TAA in Rat Based on Decreasing Intestinal Permeability,No.7142023)
文摘OBJECTIVE: To investigate the protective effects and underlying mechanism of Qingdu decoction(QDD) on experimental rats with severe liver injury induced by thioacetamide(TAA).METHODS: A total of 40 Wistar rats were randomly divided into normal group(n = 10) and experimental group(n = 30). Rats were administrated the same content of saline in normal group. The rats inthe experimental group were pretreated with TAA at dose of 12 mg/kg lasting 8 weeks, and from 9th week to 12 th week, with TAA at concentration of 36mg/kg. During the 9th week to 12 th week period,the rats were randomly divided into three subgroups(n = 10 each) simultaneously based on the treatment categories: model group, lactulose(LA,3.5 m L/kg) group and QDD(5.95 g/kg) group, orally once per day respectively. At the 12 th week, the content of serum alanine transaminase(ALT), aspartate transaminase(AST), total bilirubin(TBIL), endotoxin(ET) and tumor necrosis factor α(TNF-α) was detected by automatic biochemical analyzer. The plasma prothrombin time(PT), prothrombin time-international normalized ratio(PTR) and prothrombin time activity(PTA) were measured by automatic coagulation analyzer. The level of lipopolysaccharide(LPS)-binding protein(LBP), cluster differentiation 14(CD14) and Toll-like receptor 4(TLR4) expressions was measured by both western blot(WB) and real-time polymerase chain reaction(real-time PCR).RESULTS: Compared with the model group, hepatic morphology in the QDD group was improved under light microscope and transmission electron microscope; at the same time, the contents of serum ALT, AST, TBIL, ET and TNF-α, and level of LBP, CD14 and TLR4 expressions in liver tissues were significantly decreased compared with the model group(P < 0.05), while PTA in the QDD group was enhanced(P < 0.05).CONCLUSION: QDD has the functional effect on improving the injured liver through inhibiting the LPS/TLR4 signaling pathway thus decreasing the level of the inflammatory medicators.
