[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-272830-105":59,"doc-detail-272830-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","integrin-91-in-airway-smooth-muscle-suppresses-exaggerated-airway-narrowing-research-article","Integrin α9β1 in airway smooth muscle suppresses exaggerated airway narrowing - Research article","","Exaggerated contraction of airway smooth muscle drives asthma symptoms, yet protective mechanisms remain incompletely defined. Integrin α9β1 was found on airway smooth muscle to localize the polyamine catabolic enzyme SSAT near PIP5K1γ, the main source of PIP2 whose activity is regulated by higher-order polyamines. This proximity restrained IP3-dependent airway smooth muscle contraction. Mice lacking or blocking integrin α9β1 showed increased airway responsiveness, whereas SSAT enhancement or PIP5K1γ knockdown reduced contraction only when integrin α9β1 was functional, suggesting an integrin-recruited “brake” pathway.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/integrin-91-in-airway-smooth-muscle-suppresses-exaggerated-airway-narrowing-research-article/272830/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/integrin-91-in-airway-smooth-muscle-suppresses-exaggerated-airway-narrowing-research-article/272830.png","ImageObject",300,407,{"name":92,"@type":93},"Grenda","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-08","2026-09-15",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What role does integrin α9β1 play in airway smooth muscle contraction in asthma?","Question",{"text":112,"@type":113},"Integrin α9β1 acts as a brake on exaggerated airway smooth muscle contraction by recruiting SSAT to regulate local polyamine catabolism and suppress PIP5K1γ-driven signaling.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does loss or inhibition of integrin α9β1 affect airway narrowing?",{"text":117,"@type":113},"Mice lacking integrin α9β1 in smooth muscle show increased airway responsiveness in vivo, and integrin α9β1 loss or blocking increases airway narrowing and contraction in vitro in murine and human airways.",{"name":119,"@type":110,"acceptedAnswer":120},"Why do SSAT activation or PIP5K1γ knockdown only inhibit contraction when integrin α9β1 is functional?",{"text":121,"@type":113},"SSAT activity enhancement or PIP5K1γ knockdown inhibited airway contraction only in the presence of functional integrin α9β1, indicating the pathway requires integrin-mediated localization and coordination.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},272830,1790154464,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":41},7971474921005,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Research article  \nIntegrin α 9 β 1 in airway smooth muscle  \nsuppresses exaggerated airway narrowing  \nChun Chen,1 Makoto Kudo,1 Florentine Rutaganira,2 Hiromi Takano,1 Candace Lee,1 Amha Atakilit,1 Kathryn S. Robinett,3 Toshimitsu Uede,4 Paul J. Wolters,1 Kevan M. Shokat,2 Xiaozhu Huang,1 and Dean Sheppard1  \n1Lung Biology Center, Department of Medicine, and 2Howard Hughes Medical Institute and Department of Cellular and Molecular Pharmacology, UCSF, San Francisco, California, USA. 3Cardiopulmonary Genomics Program, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA. 4Division of Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.  \nExaggerated contraction of airway smooth muscle is the major cause of symptoms in asthma, but the mechanisms that prevent exaggerated contraction are incompletely understood. Here, we showed that integrin α9β1 on airway smooth muscle localizes the polyamine catabolizing enzyme spermidine/spermineN1-acetyltransferase (SSAT) in close proximity to the lipid kinase PIP5K1γ. As PIP5K1γ is the major source of PIP2 in airway smooth muscle and its activity is regulated by higher-order polyamines, this interaction inhibited IP3-dependent airway smooth muscle contraction. Mice lacking integrin α9β1 in smooth muscle had increased airway responsiveness in vivo, and loss or inhibition of integrin α9β1 increased in vitro airway narrowing and airway smooth muscle contraction in murine and human airways. Contraction was enhanced in control airways by the higher-order polyamine spermine or by cell-permeable PIP2, but these interventions had no effect on airways lacking integrin α9β1 or treated with integrin α9β1–blocking antibodies. Enhancement ofSSAT activity or knockdown of PIP5K1γ inhibited airway contraction, but only in the presence of functional integrin α9β1. Therefore, integrin α9β1 appears to serve asa brake on airway smooth muscle contraction by recruiting SSAT, which facilitates local catabolism of polyamines and thereby inhibits PIP5K1γ. Targeting key components of this pathway could thus lead to new treatment strategies for asthma.  \nIntroduction  \nAsthma is characterized by exaggerated narrowing of the conducting airways of the lung in response to normally trivial bronchoconstrictor stimuli. Airway narrowing in asthma is largely dependent on contraction of airway smooth muscle. However, the pathways that regulate airway smooth muscle contraction are incompletely understood.  \nIntegrins are a family of transmembrane heterodimers that participate in the translation of spatially fixed extracellular signals into a wide variety of changes in cell behavior (1, 2) . Members of this family share a number of common functions (e.g., cell attachment, spreading, and survival) and use a number of common signaling intermediates (e.g., the focal adhesion kinase and src family kinases)(2, 3). However, the diverse and largely nonoverlapping phenotypes of lines of mice expressing KO alleles of individual integrin subunit genes underscore the biological importance of integrin specificity (4–7) . Several integrins have been shown to modulate allergic asthma, including α4β1 (8–10), αLβ2 (11), αvβ6 (12), and αvβ8 (13), through effects on leukocyte recruitment, mast cell protease modulation, and modulation ofT cell cytokine production. Multiple integrins have been shown to be expressed on airway smooth muscle, where they can modulate cell proliferation and have been proposed to affect airway smooth muscle contraction, in vitro, through modulating connections between the contractile apparatus and the underlying ECM (14). Recent studies have shown that sequence variants in integrins or related genes, such as integrin β3 (15) or ADAM33 (16), are associated with asthma and allergic disease, but to date, no studies to our knowledge have demonstrated important roles for airway smooth muscle integrins in vivo.  \nConflict of interest: The authors have","cbCaitP8Tmm1dPxo","https://ap.wps.com/l/cbCaitP8Tmm1dPxo","pdf",2939708,12,"English","# Introduction\n## Integrins and airway smooth muscle in asthma\n# Results\n## Integrin α9 deletion causes airway hyperresponsiveness in vivo","[{\"question\":\"What role does integrin α9β1 play in airway smooth muscle contraction in asthma?\",\"answer\":\"Integrin α9β1 acts as a brake on exaggerated airway smooth muscle contraction by recruiting SSAT to regulate local polyamine catabolism and suppress PIP5K1γ-driven signaling.\"},{\"question\":\"How does loss or inhibition of integrin α9β1 affect airway narrowing?\",\"answer\":\"Mice lacking integrin α9β1 in smooth muscle show increased airway responsiveness in vivo, and integrin α9β1 loss or blocking increases airway narrowing and contraction in vitro in murine and human airways.\"},{\"question\":\"Why do SSAT activation or PIP5K1γ knockdown only inhibit contraction when integrin α9β1 is functional?\",\"answer\":\"SSAT activity enhancement or PIP5K1γ knockdown inhibited airway contraction only in the presence of functional integrin α9β1, indicating the pathway requires integrin-mediated localization and coordination.\"}]","Integrin α9β1 in airway smooth muscle suppresses exaggerated airway narrowing - Research article | PDF",1789467790]