Diabetic retinopathy(DR),a leading cause of visual loss,is the result of microvascular damage induced by prolonged hyperglycemia.Numerous studies have revealed the pivotal role of integrins in the pathogenesis of DR,p...Diabetic retinopathy(DR),a leading cause of visual loss,is the result of microvascular damage induced by prolonged hyperglycemia.Numerous studies have revealed the pivotal role of integrins in the pathogenesis of DR,particularly in key processes such as inflammation,vascular leakage,microthrombus formation,and angiogenesis.Consequently,targeting integrins is considered a promising strategy for the treatment of DR.This review focuses on the function of integrins in DR and their potential as therapeutic targets.It describes the molecular mechanisms through which integrins influence DR progression and summarizes the latest outcomes of integrin antagonist-based therapeutic strategies in clinical studies,evaluating their efficacy and potential challenges,which offer promise as novel treatment options for DR.展开更多
The angiogenic response is essential for the repair of ischemic brain tissue.Integrinα6(Itga6)expression has been shown to increase under hypoxic conditions and is expressed exclusively in vascular structures;however...The angiogenic response is essential for the repair of ischemic brain tissue.Integrinα6(Itga6)expression has been shown to increase under hypoxic conditions and is expressed exclusively in vascular structures;however,its role in post-ischemic angiogenesis remains poorly understood.In this study,we demonstrate that mice with endothelial cell-specific knockout of Itga6 exhibit reduced neovascularization,reduced pericyte coverage on microvessels,and accelerated breakdown of microvascular integrity in the peri-infarct area.In vitro,endothelial cells with ITGA6 knockdown display reduced proliferation,migration,and tube-formation.Mechanistically,we demonstrated that ITGA6 regulates post-stroke angiogenesis through the PI3K/Akt-eNOS-VEGFA axis.Importantly,the specific overexpression of Itga6 in endothelial cells significantly enhanced neovascularization and enhanced the integrity of microvessels,leading to improved functional recovery.Our results suggest that endothelial cell Itga6 plays a crucial role in key steps of post-stroke angiogenesis,and may represent a promising therapeutic target for promoting recovery after stroke.展开更多
Salmonella enterica serovar Typhimurium,the causative agent of gastroenteritis,is one of the most successful intracellular pathogens.Although certain host factors for Salmonella infection have been unveiled,the factor...Salmonella enterica serovar Typhimurium,the causative agent of gastroenteritis,is one of the most successful intracellular pathogens.Although certain host factors for Salmonella infection have been unveiled,the factors mediating Salmonella entry,particularly the invasion process,remain obscure.Here,we have unearthed β2 integrin,a crucial member of the integrin family,as an important host factor facilitating Salmonella invasion.It is demonstrated that overexpression of β2 integrin promotes Salmonella invasion,while the knockdown of β2 integrin significantly diminishes the extent of invasion.Moreover,Salmonella exhibits specific binding affinity towards β2 integrin,and the block of β2 integrin on cell surface substantially reduces the infection of cells in vitro.The ectodomain soluble protein of β2 integrin neutralized Salmonella infection both in cells(in vitro)and in mice(in vivo).Additionally,Salmonella protein YrbD directly interacts with β2 integrin to facilitate its invasion.To our knowledge,this study showed for the first time that the protein YrbD mediates Salmonella adhesion and internalization into host cells by interacting with β2 integrin.These findings not only broaden our understanding of the mechanisms underlying Salmonella entry,but also identify a prospective target for therapeutic control.展开更多
Integrins are heterodimeric transmembrane receptors that mediate bidirectional interactions between the intracellular cytoskeletal array and the extracellularmatrix.These interactions are critical in tissue developmen...Integrins are heterodimeric transmembrane receptors that mediate bidirectional interactions between the intracellular cytoskeletal array and the extracellularmatrix.These interactions are critical in tissue development and function by regulating gene expression and sustaining tissue architecture.In humans,the integrin family is composed of 18 alpha(α)and 8 beta(β)subunits,constituting 24 distinctαβcombinations.Based on their structure and ligandbinding properties,only a subset of integrins,8 out of 24,recognizes the arginine-glycine-aspartate(RGD)tripeptide motif in the native ligand.One of the major RGD binding integrins is integrin alpha 8 beta 1(α8β1),a central Ras homolog gene familymemberA(RHOA)-dependentmodulator highly expressed in cells with contractile function.This review focuses on the recent advances regardingα8β1 function during organ development,with a particular interest in kidney and inner ear development.We alsodiscussα8β1’s role ininjury anddisease and its importance formesenchymal to epithelial transition during cancer development.Finally,we highlightα8β1’s importance for hearing function and its future use as a potential diagnostic and therapeutic tool for disease elimination.展开更多
基金Supported by the Natural Science Foundation of Inner Mongolia,No.2022MS080572022 Autonomous Region Medical and Health Science and Technology Plan Projects,No.202202190.
文摘Diabetic retinopathy(DR),a leading cause of visual loss,is the result of microvascular damage induced by prolonged hyperglycemia.Numerous studies have revealed the pivotal role of integrins in the pathogenesis of DR,particularly in key processes such as inflammation,vascular leakage,microthrombus formation,and angiogenesis.Consequently,targeting integrins is considered a promising strategy for the treatment of DR.This review focuses on the function of integrins in DR and their potential as therapeutic targets.It describes the molecular mechanisms through which integrins influence DR progression and summarizes the latest outcomes of integrin antagonist-based therapeutic strategies in clinical studies,evaluating their efficacy and potential challenges,which offer promise as novel treatment options for DR.
基金supported by grants from the Scientific Research Foundation for Young Doctors of the Second Affiliated Hospital,Army Medical University(2022YQB041)the Chongqing Natural Science Foundation(CSTB2024NSCQ-MSX0924 and CSTB2024NSCQ-MSX0909).
文摘The angiogenic response is essential for the repair of ischemic brain tissue.Integrinα6(Itga6)expression has been shown to increase under hypoxic conditions and is expressed exclusively in vascular structures;however,its role in post-ischemic angiogenesis remains poorly understood.In this study,we demonstrate that mice with endothelial cell-specific knockout of Itga6 exhibit reduced neovascularization,reduced pericyte coverage on microvessels,and accelerated breakdown of microvascular integrity in the peri-infarct area.In vitro,endothelial cells with ITGA6 knockdown display reduced proliferation,migration,and tube-formation.Mechanistically,we demonstrated that ITGA6 regulates post-stroke angiogenesis through the PI3K/Akt-eNOS-VEGFA axis.Importantly,the specific overexpression of Itga6 in endothelial cells significantly enhanced neovascularization and enhanced the integrity of microvessels,leading to improved functional recovery.Our results suggest that endothelial cell Itga6 plays a crucial role in key steps of post-stroke angiogenesis,and may represent a promising therapeutic target for promoting recovery after stroke.
基金supported by the National Key R&D Program of China(2022YFF0710500)the the National Natural Science Foundation,China(31802192,32172853 and 32373013)+2 种基金the Natural Science Foundation of Heilongjiang Province of China(C2018070)China Postdoctoral Science Foundation(2017M620076)the Central Public-interest Scientific Institution Basal Research Fund,China(1610302022001)。
文摘Salmonella enterica serovar Typhimurium,the causative agent of gastroenteritis,is one of the most successful intracellular pathogens.Although certain host factors for Salmonella infection have been unveiled,the factors mediating Salmonella entry,particularly the invasion process,remain obscure.Here,we have unearthed β2 integrin,a crucial member of the integrin family,as an important host factor facilitating Salmonella invasion.It is demonstrated that overexpression of β2 integrin promotes Salmonella invasion,while the knockdown of β2 integrin significantly diminishes the extent of invasion.Moreover,Salmonella exhibits specific binding affinity towards β2 integrin,and the block of β2 integrin on cell surface substantially reduces the infection of cells in vitro.The ectodomain soluble protein of β2 integrin neutralized Salmonella infection both in cells(in vitro)and in mice(in vivo).Additionally,Salmonella protein YrbD directly interacts with β2 integrin to facilitate its invasion.To our knowledge,this study showed for the first time that the protein YrbD mediates Salmonella adhesion and internalization into host cells by interacting with β2 integrin.These findings not only broaden our understanding of the mechanisms underlying Salmonella entry,but also identify a prospective target for therapeutic control.
基金supported by NIH-NIDCD,5R01DC21070-0,and Creighton University’s Start-up funds to MZMs.Iman Ezzat was supported by the Department of Biomedical Sciences at Creighton University and the Bellucci Foundation pre-doctoral award.
文摘Integrins are heterodimeric transmembrane receptors that mediate bidirectional interactions between the intracellular cytoskeletal array and the extracellularmatrix.These interactions are critical in tissue development and function by regulating gene expression and sustaining tissue architecture.In humans,the integrin family is composed of 18 alpha(α)and 8 beta(β)subunits,constituting 24 distinctαβcombinations.Based on their structure and ligandbinding properties,only a subset of integrins,8 out of 24,recognizes the arginine-glycine-aspartate(RGD)tripeptide motif in the native ligand.One of the major RGD binding integrins is integrin alpha 8 beta 1(α8β1),a central Ras homolog gene familymemberA(RHOA)-dependentmodulator highly expressed in cells with contractile function.This review focuses on the recent advances regardingα8β1 function during organ development,with a particular interest in kidney and inner ear development.We alsodiscussα8β1’s role ininjury anddisease and its importance formesenchymal to epithelial transition during cancer development.Finally,we highlightα8β1’s importance for hearing function and its future use as a potential diagnostic and therapeutic tool for disease elimination.
