Notch signaling is an evolutionarily conserved intercellular signaling pathway that plays numerous crucial roles in vascular development and physiology.Compelling evidence indicates that Notch signaling is vital for v...Notch signaling is an evolutionarily conserved intercellular signaling pathway that plays numerous crucial roles in vascular development and physiology.Compelling evidence indicates that Notch signaling is vital for vascular morphogenesis including arterial and venous differentiation and endothelial tip and stalk cell specification during sprouting angiogenesis and also vessel maturation featured by mural cell differentiation and recruitment.Notch signaling is also required for vascular homeostasis in adults by keeping quiescent phalanx cells from re-entering cell cycle and by modulating the behavior of endothelial progenitor cells.We will summarize recent advances of Notch pathway in vascular biology with special emphasis on the underlying molecular mechanisms.展开更多
The retina is one of the most essential elements of vision pathway in vertebrate. The dysplasia of retina cause congenital blindness or vision disability in individuals, and the misbalance in adult retinal vascular ho...The retina is one of the most essential elements of vision pathway in vertebrate. The dysplasia of retina cause congenital blindness or vision disability in individuals, and the misbalance in adult retinal vascular homeostasis leads to neo adults, such as diabetic retinopathy or age-related macular degeneration. Many developmental signaling pathways are involved in the process of retinal development and vascular homeostasis. Among them, Notch signaling pathway has long been studied, and Notch signaling-interfered mouse models show both neural retina dysplasia and vascular abnormality. In this review, we discuss the roles of Notch signaling in the maintenance of retinal progenitor cells, specification of retinal neurons and glial cells, and the sustaining of retina vascular homeostasis, especially from the aspects of conditional knockout mouse models. The potential of Notch signal manipulation may provide a powerful cell fate- and neovascularization-controUing tool that could have important applications in treatment of retinal diseases.展开更多
Whole-body energy metabolism and cardiovascular homeostasis are tightly controlled processes that involve highly coordinated crosstalk among distal organs.This is mainly achieved by a large number of hormones released...Whole-body energy metabolism and cardiovascular homeostasis are tightly controlled processes that involve highly coordinated crosstalk among distal organs.This is mainly achieved by a large number of hormones released from each organ.Among them,fibroblast growth factor 21(FGF21)and adiponectin have recently gained considerable attention,since both of them possess multiple profound protective effects against a myriad of cardio-metabolic disorders.Despite their distinct structuresand production sites,these two hormones share striking functional similarity.This dichotomy is recently reconciled by the demonstration of the FGF21-adiponectin axis.In adipocytes,both transcription and secretion of adiponectin are strongly induced by FGF21,which is partially dependent on PPARg activity.Furthermore,the glucose-lowering,lipid-clearing,and anti-atherosclerotic functions of FGF21 are diminished in adiponectin-null mice,suggesting that adiponectin serves as an obligatory mediator of FGF21-elicited metabolic and vascular benefits.However,in both animals and human subjects with obesity,circulating FGF21 levels are increased whereas plasma adiponectin concentrations are reduced,perhaps due to FGF21 resistance,suggesting that dysfunctional FGF21-adiponectin axis is an important contributor to the pathogenesis of obesity-related cardio-metabolic syndrome.The FGF21-adiponectin axis protects against a cluster of cardio-metabolic disorders via mediating multi-organ communications,and is a promising target for therapeutic interventions of these chronic diseases.展开更多
背景:骨关节炎是一种常见的由关节软骨退行性改变所导致的关节慢性炎症,越来越多的研究表明机械应力与骨关节炎的发展密切相关。Hippo通路既参与机体组织细胞发育又是机械应力的效应因子,参与调控骨代谢和软骨代谢。目的:通过调控Hippo...背景:骨关节炎是一种常见的由关节软骨退行性改变所导致的关节慢性炎症,越来越多的研究表明机械应力与骨关节炎的发展密切相关。Hippo通路既参与机体组织细胞发育又是机械应力的效应因子,参与调控骨代谢和软骨代谢。目的:通过调控Hippo通路可能成为干预骨关节炎的新靶点之一,因而此文通过对机械应力调控Hippo通路影响骨关节炎的研究进行综述,以期为骨关节炎的发病机制提供思路并对骨关节炎的治疗方法提供新的理论依据。方法:采用PubMed、Web of Science、Embase、中国知网、维普及万方数据库进行文献检索,检索各数据库建库至2023年有关机械应力对骨关节炎的影响及机械应力、Hippo通路与骨关节炎相关的所有文献,最终纳入75篇文献进行综述。结果与结论:①不同机械应力对骨关节炎的细胞增殖凋亡与分化、骨关节炎症与血管稳态发挥不同的作用;②坚硬细胞外基质、低细胞密度、中等剪切力、中等拉伸力及压缩力通过活化YAP/TAZ可达到细胞增殖、成骨分化、血管稳态及抑制炎症反应的作用;③软细胞外基质、高细胞密度、过度剪切力、过度拉伸力及压缩力通过失活YAP/TAZ进而抑制细胞增殖、促软骨分化、破坏血管稳态及促进炎症反应,促进骨关节炎进程。展开更多
Vascular remodeling and angiogenesis are two key processes in the maintenance of vascular homeostasis and involved in a wide array of vascular pathologies. Following these processes, extracellular matrix (ECM) provide...Vascular remodeling and angiogenesis are two key processes in the maintenance of vascular homeostasis and involved in a wide array of vascular pathologies. Following these processes, extracellular matrix (ECM) provides the mechanical foundation for vascular walls. Lysyl oxidase (LOX), the key matrix-modifying enzyme, has been demonstrated to significantly affect structural abnormality and dysfunction in the blood vessels. The role of LOX in vascular remodeling and angiogenesis has always been the subject in the current medical research. Therefore, we presently make a summarization of the biosynthesis of LOX and the mechanisms involved in vascular remodeling and angiogenesis, as well as the role of LOX in diseases associated with vascular abnormalities and the therapeutic potential via targeting LOX. In particular, we give a proposal that LOX likely reshapes matrisome-associated genes expressions in the regulation of vascular remodeling and angiogenesis, which serves as a mechanistic insight into the critical role of LOX in these two aspects. Additionally, LOX has also dual effects on the vascular dysfunction, namely, inhibition of LOX for improving hypertension, restenosis and malignant tumor while activation of LOX for curing arterial aneurysm and dissection. LOX-targeted therapy may provide a promising therapeutic strategy for the treatment of various vascular pathologies associated with vascular remodeling and angiogenesis.展开更多
基金supported by the National Natural Science Foundation of China(91339115,31370769,30830067)
文摘Notch signaling is an evolutionarily conserved intercellular signaling pathway that plays numerous crucial roles in vascular development and physiology.Compelling evidence indicates that Notch signaling is vital for vascular morphogenesis including arterial and venous differentiation and endothelial tip and stalk cell specification during sprouting angiogenesis and also vessel maturation featured by mural cell differentiation and recruitment.Notch signaling is also required for vascular homeostasis in adults by keeping quiescent phalanx cells from re-entering cell cycle and by modulating the behavior of endothelial progenitor cells.We will summarize recent advances of Notch pathway in vascular biology with special emphasis on the underlying molecular mechanisms.
基金supported by the grants from the Natural Science Foundation of China (Nos.30770693 and 30830067)the Ministry of Science and Technology of China (No. 2009CB521706)
文摘The retina is one of the most essential elements of vision pathway in vertebrate. The dysplasia of retina cause congenital blindness or vision disability in individuals, and the misbalance in adult retinal vascular homeostasis leads to neo adults, such as diabetic retinopathy or age-related macular degeneration. Many developmental signaling pathways are involved in the process of retinal development and vascular homeostasis. Among them, Notch signaling pathway has long been studied, and Notch signaling-interfered mouse models show both neural retina dysplasia and vascular abnormality. In this review, we discuss the roles of Notch signaling in the maintenance of retinal progenitor cells, specification of retinal neurons and glial cells, and the sustaining of retina vascular homeostasis, especially from the aspects of conditional knockout mouse models. The potential of Notch signal manipulation may provide a powerful cell fate- and neovascularization-controUing tool that could have important applications in treatment of retinal diseases.
基金supported by General Research Fund (17124714)from Research Grant Council of Hong Kongthe National 973 Basic Research Program of China (2015CB553603)HKU matching fund for the State Key Laboratory of Pharmaceutical Biotechnology。
文摘Whole-body energy metabolism and cardiovascular homeostasis are tightly controlled processes that involve highly coordinated crosstalk among distal organs.This is mainly achieved by a large number of hormones released from each organ.Among them,fibroblast growth factor 21(FGF21)and adiponectin have recently gained considerable attention,since both of them possess multiple profound protective effects against a myriad of cardio-metabolic disorders.Despite their distinct structuresand production sites,these two hormones share striking functional similarity.This dichotomy is recently reconciled by the demonstration of the FGF21-adiponectin axis.In adipocytes,both transcription and secretion of adiponectin are strongly induced by FGF21,which is partially dependent on PPARg activity.Furthermore,the glucose-lowering,lipid-clearing,and anti-atherosclerotic functions of FGF21 are diminished in adiponectin-null mice,suggesting that adiponectin serves as an obligatory mediator of FGF21-elicited metabolic and vascular benefits.However,in both animals and human subjects with obesity,circulating FGF21 levels are increased whereas plasma adiponectin concentrations are reduced,perhaps due to FGF21 resistance,suggesting that dysfunctional FGF21-adiponectin axis is an important contributor to the pathogenesis of obesity-related cardio-metabolic syndrome.The FGF21-adiponectin axis protects against a cluster of cardio-metabolic disorders via mediating multi-organ communications,and is a promising target for therapeutic interventions of these chronic diseases.
文摘背景:骨关节炎是一种常见的由关节软骨退行性改变所导致的关节慢性炎症,越来越多的研究表明机械应力与骨关节炎的发展密切相关。Hippo通路既参与机体组织细胞发育又是机械应力的效应因子,参与调控骨代谢和软骨代谢。目的:通过调控Hippo通路可能成为干预骨关节炎的新靶点之一,因而此文通过对机械应力调控Hippo通路影响骨关节炎的研究进行综述,以期为骨关节炎的发病机制提供思路并对骨关节炎的治疗方法提供新的理论依据。方法:采用PubMed、Web of Science、Embase、中国知网、维普及万方数据库进行文献检索,检索各数据库建库至2023年有关机械应力对骨关节炎的影响及机械应力、Hippo通路与骨关节炎相关的所有文献,最终纳入75篇文献进行综述。结果与结论:①不同机械应力对骨关节炎的细胞增殖凋亡与分化、骨关节炎症与血管稳态发挥不同的作用;②坚硬细胞外基质、低细胞密度、中等剪切力、中等拉伸力及压缩力通过活化YAP/TAZ可达到细胞增殖、成骨分化、血管稳态及抑制炎症反应的作用;③软细胞外基质、高细胞密度、过度剪切力、过度拉伸力及压缩力通过失活YAP/TAZ进而抑制细胞增殖、促软骨分化、破坏血管稳态及促进炎症反应,促进骨关节炎进程。
基金funded by the National Natural Science Foundation of China(No.81974502 and 81671293)Natural Science Foundation of Hunan Province(No.2020JJ3061).
文摘Vascular remodeling and angiogenesis are two key processes in the maintenance of vascular homeostasis and involved in a wide array of vascular pathologies. Following these processes, extracellular matrix (ECM) provides the mechanical foundation for vascular walls. Lysyl oxidase (LOX), the key matrix-modifying enzyme, has been demonstrated to significantly affect structural abnormality and dysfunction in the blood vessels. The role of LOX in vascular remodeling and angiogenesis has always been the subject in the current medical research. Therefore, we presently make a summarization of the biosynthesis of LOX and the mechanisms involved in vascular remodeling and angiogenesis, as well as the role of LOX in diseases associated with vascular abnormalities and the therapeutic potential via targeting LOX. In particular, we give a proposal that LOX likely reshapes matrisome-associated genes expressions in the regulation of vascular remodeling and angiogenesis, which serves as a mechanistic insight into the critical role of LOX in these two aspects. Additionally, LOX has also dual effects on the vascular dysfunction, namely, inhibition of LOX for improving hypertension, restenosis and malignant tumor while activation of LOX for curing arterial aneurysm and dissection. LOX-targeted therapy may provide a promising therapeutic strategy for the treatment of various vascular pathologies associated with vascular remodeling and angiogenesis.
