Drought stress impairs crop growth and development.BEL1-like family transcription factors may be involved in plant response to drought stress,but little is known of the molecular mechanism by which these proteins regu...Drought stress impairs crop growth and development.BEL1-like family transcription factors may be involved in plant response to drought stress,but little is known of the molecular mechanism by which these proteins regulate plant response and defense to drought stress.Here we show that the BEL1-like transcription factor GhBLH5-A05 functions in cotton(Gossypium hirsutum)response and defense to drought stress.Expression of GhBLH5-A05 in cotton was induced by drought stress.Overexpression of GhBLH5-A05 in both Arabidopsis and cotton increased drought tolerance,whereas silencing GhBLH5-A05 in cotton resulted in elevated sensitivity to drought stress.GhBLH5-A05 binds to cis elements in the promoters of GhRD20-A09 and GhDREB2C-D05 to activate the expression of these genes.GhBLH5-A05 interacted with the KNOX transcription factor GhKNAT6-A03.Co-expression of GhBLH5-A05 and GhKNAT6-A03 increased the transcription of GhRD20-A09 and GhDREB2C-D05.We conclude that GhBLH5-A05 acts as a regulatory factor with GhKNAT6-A03 functioning in cotton response to drought stress by activating the expression of the drought-responsive genes GhRD20-A09 and GhDREB2C-D05.展开更多
BACKGROUND Defective neutrophil regulation in inflammatory bowel disease(IBD)is thought to play an important role in the onset or manifestation of IBD,as it could lead to damage of the intestinal mucosal barrier by th...BACKGROUND Defective neutrophil regulation in inflammatory bowel disease(IBD)is thought to play an important role in the onset or manifestation of IBD,as it could lead to damage of the intestinal mucosal barrier by the infiltration of neutrophils in the inflamed mucosa and the accumulation of pathogens.Like neutrophils in the context of innate immune responses,immunoglobulin A(IgA)as an acquired immune response partakes in the defense of the intestinal epithelium.Under normal conditions,IgA contributes to the elimination of microbes,but in connection with the loss of tolerance to chitinase 3-like 1(CHI3L1)in IBD,IgA could participate in CHI3L1-mediated improved adhesion and invasion of potentially pathogenic microorganisms.The tolerance brake to CHI3L1 and the occurrence of IgA autoantibodies to this particular target,the exact role and underlying mechanisms of CHI3L1 in the pathogenesis of IBD are still unclear.AIM To determine the predictive potential of Ig subtypes of a novel serological marker,anti-CHI3L1 autoantibodies(aCHI3L1)in determining the disease phenotype,therapeutic strategy and long-term disease course in a prospective referral cohort of adult IBD patients.METHODS Sera of 257 Crohn’s disease(CD)and 180 ulcerative colitis(UC)patients from a tertiary IBD referral center of Hungary(Division of Gastroenterology,Department of Internal Medicine,Faculty of Medicine,University of Debrecen)were assayed for IgG,IgA,and secretory IgA(sIgA)type aCHI3L1 by enzyme-linked immunosorbent assay using recombinant CHI3L1,along with 86 healthy controls(HCONT).RESULTS The IgA type was more prevalent in CD than in UC(29.2%vs 11.1%)or HCONT(2.83%;P<0.0001 for both).However,sIgA subtype aCHI3L1 positivity was higher in both CD and UC patients than in HCONT(39.3%and 32.8%vs 4.65%,respectively;P<0.0001).The presence of both IgA and sIgA aCHI3L1 antibodies was associated with colonic involvement(P<0.0001 and P=0.038,respectively)in patients with CD.Complicated disease behavior at sample procurement was associated with aCHI3L1 sIgA positivity(57.1%vs 36.0%,P=0.009).IgA type aCH3L1 was more prevalent in patients with frequent relapse during the disease course in the CD group(46.9%vs 25.7%,P=0.005).In a group of patients with concomitant presence of pure inflammatory luminal disease and colon involvement at the time of diagnosis,positivity for IgA or sIgA type aCH3L1 predicted faster progression towards a complicated disease course in time-dependent models.This association disappeared after merging subgroups of different disease locations.CONCLUSION CHI3L1 is a novel neutrophil autoantigenic target in IBD.The consideration of antibody classes along with location-based prediction may transform the future of serology in IBD.展开更多
BACKGROUND The low survival rate of mesenchymal stem cells(MSCs)caused by anoikis,a form of apoptosis,limits the therapeutic efficacy of MSCs.As a proapoptotic molecule,mammalian Ste20-like kinase 1(Mst1)can increase ...BACKGROUND The low survival rate of mesenchymal stem cells(MSCs)caused by anoikis,a form of apoptosis,limits the therapeutic efficacy of MSCs.As a proapoptotic molecule,mammalian Ste20-like kinase 1(Mst1)can increase the production of reactive oxygen species(ROS),thereby promoting anoikis.Recently,we found that Mst1 inhibition could protect mouse bone marrow MSCs(mBMSCs)from H 2 O 2-induced cell apoptosis by inducing autophagy and reducing ROS production.However,the influence of Mst1 inhibition on anoikis in mBMSCs remains unclear.AIM To investigate the mechanisms by which Mst1 inhibition acts on anoikis in isolated mBMSCs.METHODS Poly-2-hydroxyethyl methacrylate-induced anoikis was used following the silencing of Mst1 expression by short hairpin RNA(shRNA)adenovirus transfection.Integrin(ITGs)were tested by flow cytometry.Autophagy and ITGα5β1 were inhibited using 3-methyladenine and small interfering RNA,respe-ctively.The alterations in anoikis were measured by Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling and anoikis assays.The levels of the anoikis-related proteins ITGα5,ITGβ1,and phospho-focal adhesion kinase and the activation of caspase 3 and the autophagy-related proteins microtubules associated protein 1 light chain 3 II/I,Beclin1 and p62 were detected by Western blotting.RESULTS In isolated mBMSCs,Mst1 expression was upregulated,and Mst1 inhibition significantly reduced cell apoptosis,induced autophagy and decreased ROS levels.Mechanistically,we found that Mst1 inhibition could upregulate ITGα5 and ITGβ1 expression but not ITGα4,ITGαv,or ITGβ3 expression.Moreover,autophagy induced by upregulated ITGα5β1 expression following Mst1 inhibition played an essential role in the protective efficacy of Mst1 inhibition in averting anoikis.CONCLUSION Mst1 inhibition ameliorated autophagy formation,increased ITGα5β1 expression,and decreased the excessive production of ROS,thereby reducing cell apoptosis in isolated mBMSCs.Based on these results,Mst1 inhibition may provide a promising strategy to overcome anoikis of implanted MSCs.展开更多
Objective:To explore the role of polycystic kidney and hepatic disease 1-like 1(PKHD1L1)in lung adenocarcinoma(LUAD).Methods:Bioinformatics tools were utilized to examine the clinical profile of PKHD1L1 and chromobox ...Objective:To explore the role of polycystic kidney and hepatic disease 1-like 1(PKHD1L1)in lung adenocarcinoma(LUAD).Methods:Bioinformatics tools were utilized to examine the clinical profile of PKHD1L1 and chromobox protein homolog 7(CBX7)in LUAD.The Cell Counting Kit-8,colony formation,terminal deoxynucleotidyl transferase dUTP nick end labeling,Transwell,and wound-healing assays were carried out to assess the proliferative,apoptotic,invasive,and migrative capacities of the cells.Furthermore,the interrelation between PKHD1L1 and CBX7 was validated using a co-immunoprecipitation assay.A LUAD mice model was constructed by subcutaneous injection of A549 cells.Finally,immunohistochemical staining was performed to evaluate CBX7 and Ki67 expression.Results:PKHD1L1 was downregulated in LUAD and predicted dismal outcomes in patients with LUAD.PKHD1L1 upregulation repressed the proliferative,invasive,and migrative capabilities of A549 cells and exacerbated the apoptotic rate.Additionally,PKHD1L1 may bind to CBX7 and positively modulate CBX7 expression.CBX7 deletion partly abrogated the effects of PKHD1L1 upregulation on the cellular biological activities in A549 cells.Furthermore,the PKHD1L1/CBX7 axis regulates the Hippo signaling pathway in A549 cells.PKHD1L1 restricted tumor growth in LUAD xenograft mice;this was partly abolished by CBX7 knockdown.Conclusion:PKHD1L1 can hinder LUAD progression by regulating CBX7-mediated Hippo signaling.展开更多
在大豆(Glycine max L.Merr.)中克隆了一个1008bp的表皮毛相关基因GmTTG1-like(Glycine max Transparent Testa Glabra 1-like);生物信息学分析表明,GmTTG1-like蛋白在结构上具有4个WD40重复(WD40-repeat)结构域,与烟草中NtTTG2(Nicotia...在大豆(Glycine max L.Merr.)中克隆了一个1008bp的表皮毛相关基因GmTTG1-like(Glycine max Transparent Testa Glabra 1-like);生物信息学分析表明,GmTTG1-like蛋白在结构上具有4个WD40重复(WD40-repeat)结构域,与烟草中NtTTG2(Nicotiana tabacum Testa Glabra 2)具有较高同源性。推测GmTTG1-like与大豆表皮毛的生物学功能有关,并可能作用于大豆发育和防卫反应过程。采用RTPCR和q-RT-PCR两种方法检测GmTTG1-like在植物根、茎、叶、花和种子中的表达。构建GmTTG1-like植物表达载体并获得可以侵染的农杆菌阳性克隆。展开更多
SOC1/TM3(SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1/Tomato MADS-box gene 3)是MADS-box家族一员,它能够整合多条开花途径的开花信号,调节植物由营养生长向生殖生长的转变。在从梅花长蕊绿萼品种中克隆到3个SOC1同源基因PmSOC1-1、P...SOC1/TM3(SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1/Tomato MADS-box gene 3)是MADS-box家族一员,它能够整合多条开花途径的开花信号,调节植物由营养生长向生殖生长的转变。在从梅花长蕊绿萼品种中克隆到3个SOC1同源基因PmSOC1-1、PmSOC1-2和PmSOC1-3的基础上,构建由CaMV35S启动子驱动的植物表达载体,并在拟南芥中过量表达,以研究其功能。通过对转基因植株表型观察发现,3个PmSOC1-like基因都具有使野生型拟南芥提前开花的作用。其中,PmSOC1-2作用最强,PmSOC1-1居中,PmSOC1-3作用最弱。对转基因拟南芥内源成花基因的qRT-PCR检测说明,PmSOC1-like基因主要是通过上调其下游花分生组织特性基因(AGL24、LFY、AP1和FUL)来促进植物开花;此外,PmSOC1-1和PmSOC1-2还导致了花瓣细丝状、花萼叶片化、花瓣和花萼宿存等花器官形态的改变,说明它们可能还具有影响花器官发育的功能。研究结果将有助于阐明梅花由营养生长向生殖生长转变的分子机制。展开更多
基金supported by the Project from the Ministry of Agriculture of China for Transgenic Research(2014ZX0800927B)the National Natural Science Foundation of China(31871667).
文摘Drought stress impairs crop growth and development.BEL1-like family transcription factors may be involved in plant response to drought stress,but little is known of the molecular mechanism by which these proteins regulate plant response and defense to drought stress.Here we show that the BEL1-like transcription factor GhBLH5-A05 functions in cotton(Gossypium hirsutum)response and defense to drought stress.Expression of GhBLH5-A05 in cotton was induced by drought stress.Overexpression of GhBLH5-A05 in both Arabidopsis and cotton increased drought tolerance,whereas silencing GhBLH5-A05 in cotton resulted in elevated sensitivity to drought stress.GhBLH5-A05 binds to cis elements in the promoters of GhRD20-A09 and GhDREB2C-D05 to activate the expression of these genes.GhBLH5-A05 interacted with the KNOX transcription factor GhKNAT6-A03.Co-expression of GhBLH5-A05 and GhKNAT6-A03 increased the transcription of GhRD20-A09 and GhDREB2C-D05.We conclude that GhBLH5-A05 acts as a regulatory factor with GhKNAT6-A03 functioning in cotton response to drought stress by activating the expression of the drought-responsive genes GhRD20-A09 and GhDREB2C-D05.
基金Supported by the German Federal Ministry of Education and Research(BMBF-Wachstumskern-PRAEMED.BIO),03WKDB2Csupported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences,BO/00232/17/5+1 种基金Research Grants of National Research Development and Innovation Office,K115818/2015/1New National Excellence Program of the Ministry of Human Capacities,ÚNKP-18-4 Bolyai Plus.
文摘BACKGROUND Defective neutrophil regulation in inflammatory bowel disease(IBD)is thought to play an important role in the onset or manifestation of IBD,as it could lead to damage of the intestinal mucosal barrier by the infiltration of neutrophils in the inflamed mucosa and the accumulation of pathogens.Like neutrophils in the context of innate immune responses,immunoglobulin A(IgA)as an acquired immune response partakes in the defense of the intestinal epithelium.Under normal conditions,IgA contributes to the elimination of microbes,but in connection with the loss of tolerance to chitinase 3-like 1(CHI3L1)in IBD,IgA could participate in CHI3L1-mediated improved adhesion and invasion of potentially pathogenic microorganisms.The tolerance brake to CHI3L1 and the occurrence of IgA autoantibodies to this particular target,the exact role and underlying mechanisms of CHI3L1 in the pathogenesis of IBD are still unclear.AIM To determine the predictive potential of Ig subtypes of a novel serological marker,anti-CHI3L1 autoantibodies(aCHI3L1)in determining the disease phenotype,therapeutic strategy and long-term disease course in a prospective referral cohort of adult IBD patients.METHODS Sera of 257 Crohn’s disease(CD)and 180 ulcerative colitis(UC)patients from a tertiary IBD referral center of Hungary(Division of Gastroenterology,Department of Internal Medicine,Faculty of Medicine,University of Debrecen)were assayed for IgG,IgA,and secretory IgA(sIgA)type aCHI3L1 by enzyme-linked immunosorbent assay using recombinant CHI3L1,along with 86 healthy controls(HCONT).RESULTS The IgA type was more prevalent in CD than in UC(29.2%vs 11.1%)or HCONT(2.83%;P<0.0001 for both).However,sIgA subtype aCHI3L1 positivity was higher in both CD and UC patients than in HCONT(39.3%and 32.8%vs 4.65%,respectively;P<0.0001).The presence of both IgA and sIgA aCHI3L1 antibodies was associated with colonic involvement(P<0.0001 and P=0.038,respectively)in patients with CD.Complicated disease behavior at sample procurement was associated with aCHI3L1 sIgA positivity(57.1%vs 36.0%,P=0.009).IgA type aCH3L1 was more prevalent in patients with frequent relapse during the disease course in the CD group(46.9%vs 25.7%,P=0.005).In a group of patients with concomitant presence of pure inflammatory luminal disease and colon involvement at the time of diagnosis,positivity for IgA or sIgA type aCH3L1 predicted faster progression towards a complicated disease course in time-dependent models.This association disappeared after merging subgroups of different disease locations.CONCLUSION CHI3L1 is a novel neutrophil autoantigenic target in IBD.The consideration of antibody classes along with location-based prediction may transform the future of serology in IBD.
基金Supported by Natural Science Foundation of Shandong Province,China,No.ZR2020MH014,No.ZR2021QH179 and No.ZR2021MH182.
文摘BACKGROUND The low survival rate of mesenchymal stem cells(MSCs)caused by anoikis,a form of apoptosis,limits the therapeutic efficacy of MSCs.As a proapoptotic molecule,mammalian Ste20-like kinase 1(Mst1)can increase the production of reactive oxygen species(ROS),thereby promoting anoikis.Recently,we found that Mst1 inhibition could protect mouse bone marrow MSCs(mBMSCs)from H 2 O 2-induced cell apoptosis by inducing autophagy and reducing ROS production.However,the influence of Mst1 inhibition on anoikis in mBMSCs remains unclear.AIM To investigate the mechanisms by which Mst1 inhibition acts on anoikis in isolated mBMSCs.METHODS Poly-2-hydroxyethyl methacrylate-induced anoikis was used following the silencing of Mst1 expression by short hairpin RNA(shRNA)adenovirus transfection.Integrin(ITGs)were tested by flow cytometry.Autophagy and ITGα5β1 were inhibited using 3-methyladenine and small interfering RNA,respe-ctively.The alterations in anoikis were measured by Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling and anoikis assays.The levels of the anoikis-related proteins ITGα5,ITGβ1,and phospho-focal adhesion kinase and the activation of caspase 3 and the autophagy-related proteins microtubules associated protein 1 light chain 3 II/I,Beclin1 and p62 were detected by Western blotting.RESULTS In isolated mBMSCs,Mst1 expression was upregulated,and Mst1 inhibition significantly reduced cell apoptosis,induced autophagy and decreased ROS levels.Mechanistically,we found that Mst1 inhibition could upregulate ITGα5 and ITGβ1 expression but not ITGα4,ITGαv,or ITGβ3 expression.Moreover,autophagy induced by upregulated ITGα5β1 expression following Mst1 inhibition played an essential role in the protective efficacy of Mst1 inhibition in averting anoikis.CONCLUSION Mst1 inhibition ameliorated autophagy formation,increased ITGα5β1 expression,and decreased the excessive production of ROS,thereby reducing cell apoptosis in isolated mBMSCs.Based on these results,Mst1 inhibition may provide a promising strategy to overcome anoikis of implanted MSCs.
基金supported by Major Clinical Research Projects of Shanghai Tenth Clinical Medical College of Nanjing Medical University(SHDC2020CR3068B).
文摘Objective:To explore the role of polycystic kidney and hepatic disease 1-like 1(PKHD1L1)in lung adenocarcinoma(LUAD).Methods:Bioinformatics tools were utilized to examine the clinical profile of PKHD1L1 and chromobox protein homolog 7(CBX7)in LUAD.The Cell Counting Kit-8,colony formation,terminal deoxynucleotidyl transferase dUTP nick end labeling,Transwell,and wound-healing assays were carried out to assess the proliferative,apoptotic,invasive,and migrative capacities of the cells.Furthermore,the interrelation between PKHD1L1 and CBX7 was validated using a co-immunoprecipitation assay.A LUAD mice model was constructed by subcutaneous injection of A549 cells.Finally,immunohistochemical staining was performed to evaluate CBX7 and Ki67 expression.Results:PKHD1L1 was downregulated in LUAD and predicted dismal outcomes in patients with LUAD.PKHD1L1 upregulation repressed the proliferative,invasive,and migrative capabilities of A549 cells and exacerbated the apoptotic rate.Additionally,PKHD1L1 may bind to CBX7 and positively modulate CBX7 expression.CBX7 deletion partly abrogated the effects of PKHD1L1 upregulation on the cellular biological activities in A549 cells.Furthermore,the PKHD1L1/CBX7 axis regulates the Hippo signaling pathway in A549 cells.PKHD1L1 restricted tumor growth in LUAD xenograft mice;this was partly abolished by CBX7 knockdown.Conclusion:PKHD1L1 can hinder LUAD progression by regulating CBX7-mediated Hippo signaling.
文摘SOC1/TM3(SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1/Tomato MADS-box gene 3)是MADS-box家族一员,它能够整合多条开花途径的开花信号,调节植物由营养生长向生殖生长的转变。在从梅花长蕊绿萼品种中克隆到3个SOC1同源基因PmSOC1-1、PmSOC1-2和PmSOC1-3的基础上,构建由CaMV35S启动子驱动的植物表达载体,并在拟南芥中过量表达,以研究其功能。通过对转基因植株表型观察发现,3个PmSOC1-like基因都具有使野生型拟南芥提前开花的作用。其中,PmSOC1-2作用最强,PmSOC1-1居中,PmSOC1-3作用最弱。对转基因拟南芥内源成花基因的qRT-PCR检测说明,PmSOC1-like基因主要是通过上调其下游花分生组织特性基因(AGL24、LFY、AP1和FUL)来促进植物开花;此外,PmSOC1-1和PmSOC1-2还导致了花瓣细丝状、花萼叶片化、花瓣和花萼宿存等花器官形态的改变,说明它们可能还具有影响花器官发育的功能。研究结果将有助于阐明梅花由营养生长向生殖生长转变的分子机制。
