Genome-wide studies have reported that Parkinson's disease is associated with abnormal expression of various growth factors. In this study, male C57BL/6 mice aged 10 weeks were used to establish Parkinson's di...Genome-wide studies have reported that Parkinson's disease is associated with abnormal expression of various growth factors. In this study, male C57BL/6 mice aged 10 weeks were used to establish Parkinson's disease models using an intraperitoneal injection of 60 mg/kg 1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine. 28 days later, 10 or 100 ng fibroblast growth factor 20 was injected intracerebroventricularly. The electrophysiological changes in the mouse hippocampus were recorded using a full-cell patch clamp. Expression of Kv4.2 in the substantia nigra was analyzed using a western blot assay. Serum malondialdehyde levels were analyzed by enzyme-linked immunosorbent assay. The motor coordination of mice was evaluated using the rotarod test. The results showed that fibroblast growth factor 20 decreased A-type potassium current in neurons of the substantia nigra, increased long-term potentiation amplitude in the hippocampus, and downregulated Kv4.2 expression. A high dose of fibroblast growth factor 20 reduced serum malondialdehyde levels and enhanced the motor coordination of mice. These findings confirm that fibroblast growth factor 20 has a therapeutic effect on the toxicity induced by l-methyl-4-phenyl-l,2,3s6-tetrahydropyridine, and its mechanism of action is associated with the inhibition of A-type K^+ currents and Kv4.2 expression. All animal procedures were approved by the Animal Care and Use Committee of Qilu Hospital of Shandong University, China in 2017 (approval No. KYLL-2017-0012).展开更多
Fibroblast growth factor (FGF) is a key regulator of developmental processes. A FGF homolog (vFGF) is found in all lepidopteran baculoviruses. Autographa californica nucleopolyhedrovirus (AcMNPV) and Bombyx mori NPV (...Fibroblast growth factor (FGF) is a key regulator of developmental processes. A FGF homolog (vFGF) is found in all lepidopteran baculoviruses. Autographa californica nucleopolyhedrovirus (AcMNPV) and Bombyx mori NPV (BmNPV) vFGFs are chemotactic factors. Here we analyzed the vfgf of Helicoverpa armigera NPV (HearNPV), a group II NPV. The HearNPV vfgf transcripts were detected from 18 to 96 h post-infection (hpi) of Hz-AM1 cells with HearNPV and encoded a 36 kDa protein, which was secreted into the culture medium. HearNPV vFGF had strong affinity to heparin, a property important for FGF signaling via an FGF receptor. Unlike its AcMNPV homolog, HearNPV vFGF specially chemoattracted Hz-AM1, but not other insect cells such as Sf9 and Se-UCR and not the mammalian cells 293 and HepG2. HearNPV vFGF is also associated with the envelope of BV but is absent in occlusion-derived virus, which coordinated to the chemotatic activity analysis.展开更多
Tacrolimus(TAC),also called FK506,is one of the classical immunosuppressants to prevent allograft rejection after liver transplantation.However,it has been proved to be associated with post-transplant hyperlipemia.The...Tacrolimus(TAC),also called FK506,is one of the classical immunosuppressants to prevent allograft rejection after liver transplantation.However,it has been proved to be associated with post-transplant hyperlipemia.The mechanism behind this is unknown,and it is urgent to explore preventive strategies for hyperlipemia after transplantation.Therefore,we established a hyperlipemia mouse model to investigate the mechanism,by injecting TAC intraperitoneally for eight weeks.After TAC treatment,the mice developed hyperlipemia(manifested as elevated triglyceride(TG)and low-density lipoprotein cholesterol(LDL-c),as well as decreased high-density lipoprotein cholesterol(HDL-c)).Accumulation of lipid droplets was observed in the liver.In addition to lipid accumulation,TAC induced inhibition of the autophagy-lysosome pathway(microtubule-associated protein 1light chain 3β(LC3B)II/I and LC3B II/actin ratios,transcription factor EB(TFEB),protein 62(P62),and lysosomal-associated membrane protein 1(LAMP1))and downregulation of fibroblast growth factor 21(FGF21)in vivo.Overexpression of FGF21may reverse TAC-induced TG accumulation.In this mouse model,the recombinant FGF21 protein ameliorated hepatic lipid accumulation and hyperlipemia through repair of the autophagy-lysosome pathway.We conclude that TAC downregulates FGF21and thus exacerbates lipid accumulation by impairing the autophagy-lysosome pathway.Recombinant FGF21 protein treatment could therefore reverse TAC-caused lipid accumulation and hypertriglyceridemia by enhancing autophagy.展开更多
文摘Genome-wide studies have reported that Parkinson's disease is associated with abnormal expression of various growth factors. In this study, male C57BL/6 mice aged 10 weeks were used to establish Parkinson's disease models using an intraperitoneal injection of 60 mg/kg 1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine. 28 days later, 10 or 100 ng fibroblast growth factor 20 was injected intracerebroventricularly. The electrophysiological changes in the mouse hippocampus were recorded using a full-cell patch clamp. Expression of Kv4.2 in the substantia nigra was analyzed using a western blot assay. Serum malondialdehyde levels were analyzed by enzyme-linked immunosorbent assay. The motor coordination of mice was evaluated using the rotarod test. The results showed that fibroblast growth factor 20 decreased A-type potassium current in neurons of the substantia nigra, increased long-term potentiation amplitude in the hippocampus, and downregulated Kv4.2 expression. A high dose of fibroblast growth factor 20 reduced serum malondialdehyde levels and enhanced the motor coordination of mice. These findings confirm that fibroblast growth factor 20 has a therapeutic effect on the toxicity induced by l-methyl-4-phenyl-l,2,3s6-tetrahydropyridine, and its mechanism of action is associated with the inhibition of A-type K^+ currents and Kv4.2 expression. All animal procedures were approved by the Animal Care and Use Committee of Qilu Hospital of Shandong University, China in 2017 (approval No. KYLL-2017-0012).
基金National Nature Science Foundations of China (30325002,30670077)National Basic Research Priorities Program of China (2003CB1140).
文摘Fibroblast growth factor (FGF) is a key regulator of developmental processes. A FGF homolog (vFGF) is found in all lepidopteran baculoviruses. Autographa californica nucleopolyhedrovirus (AcMNPV) and Bombyx mori NPV (BmNPV) vFGFs are chemotactic factors. Here we analyzed the vfgf of Helicoverpa armigera NPV (HearNPV), a group II NPV. The HearNPV vfgf transcripts were detected from 18 to 96 h post-infection (hpi) of Hz-AM1 cells with HearNPV and encoded a 36 kDa protein, which was secreted into the culture medium. HearNPV vFGF had strong affinity to heparin, a property important for FGF signaling via an FGF receptor. Unlike its AcMNPV homolog, HearNPV vFGF specially chemoattracted Hz-AM1, but not other insect cells such as Sf9 and Se-UCR and not the mammalian cells 293 and HepG2. HearNPV vFGF is also associated with the envelope of BV but is absent in occlusion-derived virus, which coordinated to the chemotatic activity analysis.
基金supported by the National Key Research and Development Program of China(No.2021YFA1100500)the National Natural Science Foundation of China(Nos.92159202,81930016,and 82102910)+3 种基金the Key Research&Development Plan of Zhejiang Province(No.2019C03050)the Construction Fund of Key Medical Disciplines of Hangzhou(No.0020200093)the Postdoctoral Science Foundation(No.2020M671762)the Medical and Health Technology Program in Zhejiang Province(No.WKJ-ZJ-2120),China.
文摘Tacrolimus(TAC),also called FK506,is one of the classical immunosuppressants to prevent allograft rejection after liver transplantation.However,it has been proved to be associated with post-transplant hyperlipemia.The mechanism behind this is unknown,and it is urgent to explore preventive strategies for hyperlipemia after transplantation.Therefore,we established a hyperlipemia mouse model to investigate the mechanism,by injecting TAC intraperitoneally for eight weeks.After TAC treatment,the mice developed hyperlipemia(manifested as elevated triglyceride(TG)and low-density lipoprotein cholesterol(LDL-c),as well as decreased high-density lipoprotein cholesterol(HDL-c)).Accumulation of lipid droplets was observed in the liver.In addition to lipid accumulation,TAC induced inhibition of the autophagy-lysosome pathway(microtubule-associated protein 1light chain 3β(LC3B)II/I and LC3B II/actin ratios,transcription factor EB(TFEB),protein 62(P62),and lysosomal-associated membrane protein 1(LAMP1))and downregulation of fibroblast growth factor 21(FGF21)in vivo.Overexpression of FGF21may reverse TAC-induced TG accumulation.In this mouse model,the recombinant FGF21 protein ameliorated hepatic lipid accumulation and hyperlipemia through repair of the autophagy-lysosome pathway.We conclude that TAC downregulates FGF21and thus exacerbates lipid accumulation by impairing the autophagy-lysosome pathway.Recombinant FGF21 protein treatment could therefore reverse TAC-caused lipid accumulation and hypertriglyceridemia by enhancing autophagy.
