Myocardial fibrosis is a major pathogenic factor contributing to cardiac remodeling and heart failure. Recent research has indicated that micro RNAs play a crucial role in the progression of cardiac fibrosis. Bone mor...Myocardial fibrosis is a major pathogenic factor contributing to cardiac remodeling and heart failure. Recent research has indicated that micro RNAs play a crucial role in the progression of cardiac fibrosis. Bone morphogenetic protein and activin membrane-bound inhibitor(BAMBI) have been shown to alleviate myocardial fibrosis by inhibiting the transforming growth factor β1(TGF-β1) signaling pathway. Therefore, the current study aimed to elucidate the post-transcriptional regulation of BAMBI by miR-19a-3p and its role in TGF-β1-induced cardiac fibroblast activation. We found that transverse aortic constriction induced both myocardial interstitial and perivascular collagen deposition. Quantitative reverse transcription-PCR(q RT-PCR) analysis showed that the expression level of miR-19a-3p was increased in the myocardial tissues of cardiac fibrosis, and TGF-β1 induced an upregulation in miR-19a-3p expression in cardiac fibroblasts. The dual-luciferase reporter assay and q RT-PCR verified that miR-19a-3p directly bound to the 3 ′ untranslated regions of BAMBI m RNA, thereby reducing BAMBI expression and diminishing its ability to inhibit the TGF-β1 signaling pathway. Furthermore,overexpression of miR-19a-3p mimic increased the activation of TGF-β1/SMAD2/3 pathway signaling,promoting cardiac fibroblast activation. However, this activation was blocked by BAMBI overexpression. These findings imply that miR-19a-3p enhances the activation of TGF-β1/SMAD2/3 by inhibiting BAMBI, further boosting the activation of cardiac fibroblasts and contributing to myocardial fibrosis.展开更多
目的研究BAMBI基因在小鼠不同脂肪组织发育过程中的表达规律。方法利用RT-q PCR及Western blot技术检测BAMBI基因在小鼠不同类型脂肪组织、不同发育阶段(胚胎第18天、出生第0天、第21天、第8周和第6个月)及原代前体脂肪细胞分化过程中(...目的研究BAMBI基因在小鼠不同脂肪组织发育过程中的表达规律。方法利用RT-q PCR及Western blot技术检测BAMBI基因在小鼠不同类型脂肪组织、不同发育阶段(胚胎第18天、出生第0天、第21天、第8周和第6个月)及原代前体脂肪细胞分化过程中(分化第0、3、7、11天)的差异表达情况。结果随着脂肪组织的发育,BAMBI m RNA及蛋白的表达量逐渐降低;在发育的同一时间段,BAMBI m RNA在内脏白色脂肪组织较皮下白色脂肪组织表达量高,在棕色脂肪组织中表达量最低;在小鼠前体脂肪细胞诱导分化过程中,BAMBI m RNA表达量呈时间依赖性降低。结论提示BAMBI的差异表达规律与脂肪组织类型、发育阶段以及脂肪细胞分化程度密切相关,其在脂肪组织发育过程中起着重要的作用。展开更多
为研究转化生长因子-β(TGF-β)信号通路中的骨形态发生蛋白和激活素膜结合抑制剂(bone morphogenetic protein and activin membrane-bound inhibitor,BAMBI)基因对猪卵泡颗粒细胞的调控作用,本研究设计构建BAMBI干扰和过表达载体,并...为研究转化生长因子-β(TGF-β)信号通路中的骨形态发生蛋白和激活素膜结合抑制剂(bone morphogenetic protein and activin membrane-bound inhibitor,BAMBI)基因对猪卵泡颗粒细胞的调控作用,本研究设计构建BAMBI干扰和过表达载体,并将构建好的干扰(pSIREN-BAMBI-sh1、pSIREN-BAMBI-sh2、pSIREN-BAMBI-sh3)和过表达(pcDNA3.1-BAMBI)重组质粒转染猪卵泡颗粒细胞,通过实时荧光定量PCR技术进行有效片段的筛选,并对TGF-β信号通路下游基因(TGF-βRⅠ、TGF-βRⅡ、SMAD1、SMAD2、SMAD3、SMAD4、SMAD5)和细胞凋亡基因(Bax、Bcl-2)mRNA的表达水平进行检测。最后,用MTT法和流式细胞术检测BAMBI干扰和过表达对卵泡颗粒细胞增殖及凋亡的影响。结果表明,BAMBI干扰和过表达载体成功构建,pSIREN-BAMBI-sh2抑制BAMBI表达的效果最好,干扰效率最高。干扰BAMBI时,TGF-βRⅡ表达量显著上升(P<0.05),使得SMAD2、SMAD3的表达量显著上升(P<0.05);过表达BAMBI时,TGF-βRⅡ表达显著下降(P<0.05),使得SMAD2、SMAD3的表达量显著下降(P<0.05);上调BAMBI可显著抑制猪卵泡颗粒细胞增殖,极显著促进猪卵泡颗粒细胞凋亡(P<0.01)。研究结果表明,BAMBI基因显著影响猪卵泡颗粒细胞的生长发育,可能通过调节TGF-β信号通路间接影响猪的繁殖性能。展开更多
目的研究骨成形蛋白-激活素膜结合阻断因子(BMP and activin membrane-bound inhibitor,BAMBI)与卵巢癌耐药性之间的关系。方法运用GEPIA在线工具分析BAMBI在正常卵巢组织与卵巢癌组织中的表达差异;基于GEO数据库分析BAMBI在顺铂敏感性...目的研究骨成形蛋白-激活素膜结合阻断因子(BMP and activin membrane-bound inhibitor,BAMBI)与卵巢癌耐药性之间的关系。方法运用GEPIA在线工具分析BAMBI在正常卵巢组织与卵巢癌组织中的表达差异;基于GEO数据库分析BAMBI在顺铂敏感性与顺铂耐药性的卵巢癌细胞株中的表达差异;CTRP数据库进行卵巢癌细胞BAMBI表达量与化疗药物敏感性相关性分析;综合运用基因互做分析、基因通路富集、基因相关性分析、文本挖掘、miRNA-mRNA相互作用分析等生物信息学方法进一步证明BAMBI调节卵巢癌耐药性及探索其内在机制。结果BAMBI在卵巢癌组织的表达显著低于正常卵巢,同时对顺铂耐药的卵巢癌细胞系中BAMBI表达量也显著低于对顺铂敏感的卵巢癌细胞系,与BAMBI高度关联性的基因大部分与卵巢癌耐药性有关;基因通路富集对与BAMBI相关联的基因分析发现,TGF-β(转化生长因子-β)信号通路、Hippo信号通路、细胞因子及其受体等通路的富集程度最高;TSPAN5与BAMBI高度相关,并且在卵巢癌和顺铂耐药的细胞株A2780中低表达;文本挖掘显示,细胞增殖、生长、凋亡过程以及信号转导等生物过程同时与BAMBI蛋白、卵巢癌、肿瘤耐药性具有显著的关联性;miRNA-mRNA互作分析发现,靶向于BAMBI的15个miRNA皆与卵巢癌耐药性或其他肿瘤耐药性相关。结论低表达BAMBI介导了卵巢癌的耐药性的发生。展开更多
BAMB I(bone morphogenetic prote in and activin m embrane-bound inh ib itor,BAMB I)是TGF-β信号转导通路的伪受体,与TGF-βⅠ型受体结构相似,但不具有同样的活性。它可以竞争性地与Ⅱ型受体结合,诱导配体———TGF-β超家族成员(T...BAMB I(bone morphogenetic prote in and activin m embrane-bound inh ib itor,BAMB I)是TGF-β信号转导通路的伪受体,与TGF-βⅠ型受体结构相似,但不具有同样的活性。它可以竞争性地与Ⅱ型受体结合,诱导配体———TGF-β超家族成员(TGF-β、骨形态发生蛋白、激活素等)形成配体受体复合物,使胞质区的SMAD蛋白无法被磷酸化而激活,从而阻断TGF-β家族的信号转导,影响一系列下游基因的表达。BAMB I因其结构上的特点而广泛参与TGF-β信号转导的调控,并由此在各组织器官的肿瘤与疾病的发生及演进中起重要的作用。展开更多
目的:探讨sh RNA干扰骨形成蛋白和激活素的穿膜抑制剂(bone morphogenetic protein and activin membrane bound inhibitor,BAMBI)基因对人结肠癌SW480细胞增殖、凋亡、侵袭和迁移的影响及其作用机制。方法:转染SW480细胞sh-BAMBI成功后...目的:探讨sh RNA干扰骨形成蛋白和激活素的穿膜抑制剂(bone morphogenetic protein and activin membrane bound inhibitor,BAMBI)基因对人结肠癌SW480细胞增殖、凋亡、侵袭和迁移的影响及其作用机制。方法:转染SW480细胞sh-BAMBI成功后,实时定量PCR(q RT-PCR)和Western blotting检测BAMBI m RNA和蛋白表达水平,MTT法检测SW480细胞增殖能力,Hoechst33258染色检测细胞凋亡情况,Transwell实验检测细胞侵袭能力,划痕实验检测SW480细胞迁移能力,Western blotting检测TGF-β/Smad2通路相关蛋白的表达水平。结果:转染成功后sh-BAMBI组中BAMBI的m RNA和蛋白水平均低于对照组(P<0.05);与对照组相比,sh-BAMBI组细胞增殖率明显降低(P<0.05)、细胞凋亡率显著升高(P<0.01),同时其侵袭和迁移能力明显减弱(均P<0.05)。sh-BAMBI组TGF-β蛋白水平和p-Smad2/Smad2比值明显高于对照组(P<0.05)。结论:sh RNA干扰BAMBI可诱导人结肠癌SW480细胞凋亡并抑制细胞增殖、侵袭和迁移,其机制可能与激活TGFβ/Smad2通路有关。展开更多
Skeletal muscle plays a significant role in both local and systemic energy metabolism.The current investigation aims to explore the role of the Bambi gene in skeletal muscle,focusing on its implications for muscle hyp...Skeletal muscle plays a significant role in both local and systemic energy metabolism.The current investigation aims to explore the role of the Bambi gene in skeletal muscle,focusing on its implications for muscle hypertrophy and systemic metabolism.We hypothesize that skeletal muscle-specific deletion of Bambi induces muscle hypertrophy,improves metabolic performance,and activates thermogenic adipocytes via the reprogramming of progenitor of iWAT,offering potential therapeutic strategies for metabolic syndromes.Leveraging the Chromatin immunoprecipitation(ChIP)-seq and bioinformatics analysis,Bambi gene is shown to be a direct target of HIF2α,which is further confirmed by ChIP-qPCR and promoter luciferase assay.Skeletal muscle-specific Bambi deletion led to significant muscle hypertrophy and improved metabolic parameters,even under high-fat diet conditions.This deletion induced metabolic reprogramming of stromal vascular fractions(SVFs)into thermogenic adipocytes,contributing to systemic metabolic improvements,potentially through the secretory factor.Notably,mice with skeletal muscle-specific Bambi deletion demonstrate resistance to high-fat diet-induced metabolic disorders,highlighting a potential therapeutic pathway for metabolic syndrome management.Thus,skeletal muscle-specific deletion of Bambi triggers muscle growth,enhances metabolic performance,and activates thermogenic adipocytes.These findings suggest Bambi as a novel therapeutic target for metabolic syndromes,providing new insights into the interaction between muscle hypertrophy and systemic metabolic improvement.The study underscores the potential of manipulating muscle physiology to regulate whole-body metabolism,offering a novel perspective on treating metabolic disorders.展开更多
基金National Natural Science Foundation of China (Grant Nos. 82070234 and 82100254)。
文摘Myocardial fibrosis is a major pathogenic factor contributing to cardiac remodeling and heart failure. Recent research has indicated that micro RNAs play a crucial role in the progression of cardiac fibrosis. Bone morphogenetic protein and activin membrane-bound inhibitor(BAMBI) have been shown to alleviate myocardial fibrosis by inhibiting the transforming growth factor β1(TGF-β1) signaling pathway. Therefore, the current study aimed to elucidate the post-transcriptional regulation of BAMBI by miR-19a-3p and its role in TGF-β1-induced cardiac fibroblast activation. We found that transverse aortic constriction induced both myocardial interstitial and perivascular collagen deposition. Quantitative reverse transcription-PCR(q RT-PCR) analysis showed that the expression level of miR-19a-3p was increased in the myocardial tissues of cardiac fibrosis, and TGF-β1 induced an upregulation in miR-19a-3p expression in cardiac fibroblasts. The dual-luciferase reporter assay and q RT-PCR verified that miR-19a-3p directly bound to the 3 ′ untranslated regions of BAMBI m RNA, thereby reducing BAMBI expression and diminishing its ability to inhibit the TGF-β1 signaling pathway. Furthermore,overexpression of miR-19a-3p mimic increased the activation of TGF-β1/SMAD2/3 pathway signaling,promoting cardiac fibroblast activation. However, this activation was blocked by BAMBI overexpression. These findings imply that miR-19a-3p enhances the activation of TGF-β1/SMAD2/3 by inhibiting BAMBI, further boosting the activation of cardiac fibroblasts and contributing to myocardial fibrosis.
文摘目的研究BAMBI基因在小鼠不同脂肪组织发育过程中的表达规律。方法利用RT-q PCR及Western blot技术检测BAMBI基因在小鼠不同类型脂肪组织、不同发育阶段(胚胎第18天、出生第0天、第21天、第8周和第6个月)及原代前体脂肪细胞分化过程中(分化第0、3、7、11天)的差异表达情况。结果随着脂肪组织的发育,BAMBI m RNA及蛋白的表达量逐渐降低;在发育的同一时间段,BAMBI m RNA在内脏白色脂肪组织较皮下白色脂肪组织表达量高,在棕色脂肪组织中表达量最低;在小鼠前体脂肪细胞诱导分化过程中,BAMBI m RNA表达量呈时间依赖性降低。结论提示BAMBI的差异表达规律与脂肪组织类型、发育阶段以及脂肪细胞分化程度密切相关,其在脂肪组织发育过程中起着重要的作用。
文摘为研究转化生长因子-β(TGF-β)信号通路中的骨形态发生蛋白和激活素膜结合抑制剂(bone morphogenetic protein and activin membrane-bound inhibitor,BAMBI)基因对猪卵泡颗粒细胞的调控作用,本研究设计构建BAMBI干扰和过表达载体,并将构建好的干扰(pSIREN-BAMBI-sh1、pSIREN-BAMBI-sh2、pSIREN-BAMBI-sh3)和过表达(pcDNA3.1-BAMBI)重组质粒转染猪卵泡颗粒细胞,通过实时荧光定量PCR技术进行有效片段的筛选,并对TGF-β信号通路下游基因(TGF-βRⅠ、TGF-βRⅡ、SMAD1、SMAD2、SMAD3、SMAD4、SMAD5)和细胞凋亡基因(Bax、Bcl-2)mRNA的表达水平进行检测。最后,用MTT法和流式细胞术检测BAMBI干扰和过表达对卵泡颗粒细胞增殖及凋亡的影响。结果表明,BAMBI干扰和过表达载体成功构建,pSIREN-BAMBI-sh2抑制BAMBI表达的效果最好,干扰效率最高。干扰BAMBI时,TGF-βRⅡ表达量显著上升(P<0.05),使得SMAD2、SMAD3的表达量显著上升(P<0.05);过表达BAMBI时,TGF-βRⅡ表达显著下降(P<0.05),使得SMAD2、SMAD3的表达量显著下降(P<0.05);上调BAMBI可显著抑制猪卵泡颗粒细胞增殖,极显著促进猪卵泡颗粒细胞凋亡(P<0.01)。研究结果表明,BAMBI基因显著影响猪卵泡颗粒细胞的生长发育,可能通过调节TGF-β信号通路间接影响猪的繁殖性能。
文摘目的研究骨成形蛋白-激活素膜结合阻断因子(BMP and activin membrane-bound inhibitor,BAMBI)与卵巢癌耐药性之间的关系。方法运用GEPIA在线工具分析BAMBI在正常卵巢组织与卵巢癌组织中的表达差异;基于GEO数据库分析BAMBI在顺铂敏感性与顺铂耐药性的卵巢癌细胞株中的表达差异;CTRP数据库进行卵巢癌细胞BAMBI表达量与化疗药物敏感性相关性分析;综合运用基因互做分析、基因通路富集、基因相关性分析、文本挖掘、miRNA-mRNA相互作用分析等生物信息学方法进一步证明BAMBI调节卵巢癌耐药性及探索其内在机制。结果BAMBI在卵巢癌组织的表达显著低于正常卵巢,同时对顺铂耐药的卵巢癌细胞系中BAMBI表达量也显著低于对顺铂敏感的卵巢癌细胞系,与BAMBI高度关联性的基因大部分与卵巢癌耐药性有关;基因通路富集对与BAMBI相关联的基因分析发现,TGF-β(转化生长因子-β)信号通路、Hippo信号通路、细胞因子及其受体等通路的富集程度最高;TSPAN5与BAMBI高度相关,并且在卵巢癌和顺铂耐药的细胞株A2780中低表达;文本挖掘显示,细胞增殖、生长、凋亡过程以及信号转导等生物过程同时与BAMBI蛋白、卵巢癌、肿瘤耐药性具有显著的关联性;miRNA-mRNA互作分析发现,靶向于BAMBI的15个miRNA皆与卵巢癌耐药性或其他肿瘤耐药性相关。结论低表达BAMBI介导了卵巢癌的耐药性的发生。
文摘BAMB I(bone morphogenetic prote in and activin m embrane-bound inh ib itor,BAMB I)是TGF-β信号转导通路的伪受体,与TGF-βⅠ型受体结构相似,但不具有同样的活性。它可以竞争性地与Ⅱ型受体结合,诱导配体———TGF-β超家族成员(TGF-β、骨形态发生蛋白、激活素等)形成配体受体复合物,使胞质区的SMAD蛋白无法被磷酸化而激活,从而阻断TGF-β家族的信号转导,影响一系列下游基因的表达。BAMB I因其结构上的特点而广泛参与TGF-β信号转导的调控,并由此在各组织器官的肿瘤与疾病的发生及演进中起重要的作用。
基金supported by National Natural Science Foundation of China(82072436)Guangdong Basic and Applied Basic Research Foundation(2020B1515020046)‘GDAS’Project of Science and Technology Development(2021GDASYL-20210102003,2018GDASCX-0102)。
文摘Skeletal muscle plays a significant role in both local and systemic energy metabolism.The current investigation aims to explore the role of the Bambi gene in skeletal muscle,focusing on its implications for muscle hypertrophy and systemic metabolism.We hypothesize that skeletal muscle-specific deletion of Bambi induces muscle hypertrophy,improves metabolic performance,and activates thermogenic adipocytes via the reprogramming of progenitor of iWAT,offering potential therapeutic strategies for metabolic syndromes.Leveraging the Chromatin immunoprecipitation(ChIP)-seq and bioinformatics analysis,Bambi gene is shown to be a direct target of HIF2α,which is further confirmed by ChIP-qPCR and promoter luciferase assay.Skeletal muscle-specific Bambi deletion led to significant muscle hypertrophy and improved metabolic parameters,even under high-fat diet conditions.This deletion induced metabolic reprogramming of stromal vascular fractions(SVFs)into thermogenic adipocytes,contributing to systemic metabolic improvements,potentially through the secretory factor.Notably,mice with skeletal muscle-specific Bambi deletion demonstrate resistance to high-fat diet-induced metabolic disorders,highlighting a potential therapeutic pathway for metabolic syndrome management.Thus,skeletal muscle-specific deletion of Bambi triggers muscle growth,enhances metabolic performance,and activates thermogenic adipocytes.These findings suggest Bambi as a novel therapeutic target for metabolic syndromes,providing new insights into the interaction between muscle hypertrophy and systemic metabolic improvement.The study underscores the potential of manipulating muscle physiology to regulate whole-body metabolism,offering a novel perspective on treating metabolic disorders.
