{"id":"https://openalex.org/W7225780911","doi":"https://doi.org/10.3389/fimmu.2026.1947334","title":"ISM1 promotes alveolar fluid clearance in acute lung injury by targeting cell-surface GRP78 and inhibiting PI3K/AKT/mTOR signaling pathway","display_name":"ISM1 promotes alveolar fluid clearance in acute lung injury by targeting cell-surface GRP78 and inhibiting PI3K/AKT/mTOR signaling pathway","publication_year":2026,"publication_date":"2026-11-11","ids":{"openalex":"https://openalex.org/W7225780911","doi":"https://doi.org/10.3389/fimmu.2026.1947334"},"language":"en","primary_location":{"id":"doi:10.3389/fimmu.2026.1947334","doi":"https://doi.org/10.3389/fimmu.2026.1947334","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fimmu.2026.1947334","pdf_url":"https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1947334/pdf","source":{"id":"https://openalex.org/S2595292759","display_name":"Frontiers in Immunology","issn_l":"1664-3224","issn":["1664-3224"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","jufo-1","ki-jl-1","medline","norway-1","oarl","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Immunology","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","doaj"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1947334/pdf","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5022917283","display_name":"\u5218\u5b66\u73b2","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210097509","display_name":"Second Affiliated Hospital of Chongqing Medical University","ror":"https://ror.org/00r67fz39","country_code":"CN","type":"healthcare","lineage":["https://openalex.org/I4210097509"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Xueling Liu","raw_affiliation_strings":["Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Chongqing Medical University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Chongqing Medical University","institution_ids":["https://openalex.org/I4210097509"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5161451690","display_name":"Jiahao Li","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210097509","display_name":"Second Affiliated Hospital of Chongqing Medical University","ror":"https://ror.org/00r67fz39","country_code":"CN","type":"healthcare","lineage":["https://openalex.org/I4210097509"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Jiahao Li","raw_affiliation_strings":["Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Chongqing Medical University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Chongqing Medical University","institution_ids":["https://openalex.org/I4210097509"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5133301285","display_name":"ting li","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210097509","display_name":"Second Affiliated Hospital of Chongqing Medical University","ror":"https://ror.org/00r67fz39","country_code":"CN","type":"healthcare","lineage":["https://openalex.org/I4210097509"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Ting Li","raw_affiliation_strings":["Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Chongqing Medical University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Chongqing Medical University","institution_ids":["https://openalex.org/I4210097509"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5161440231","display_name":"Jialing Bu","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210097509","display_name":"Second Affiliated Hospital of Chongqing Medical University","ror":"https://ror.org/00r67fz39","country_code":"CN","type":"healthcare","lineage":["https://openalex.org/I4210097509"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Jialing Bu","raw_affiliation_strings":["Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Chongqing Medical University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Chongqing Medical University","institution_ids":["https://openalex.org/I4210097509"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5100459953","display_name":"Zhen Yang","orcid":"https://orcid.org/0000-0001-8293-3581","observed_orcids":["https://orcid.org/0000-0001-8293-3581"]},"institutions":[{"id":"https://openalex.org/I4210097509","display_name":"Second Affiliated Hospital of Chongqing Medical University","ror":"https://ror.org/00r67fz39","country_code":"CN","type":"healthcare","lineage":["https://openalex.org/I4210097509"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Zhen Yang","raw_affiliation_strings":["Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Chongqing Medical University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Chongqing Medical University","institution_ids":["https://openalex.org/I4210097509"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5056206602","display_name":"Wang Deng","orcid":"https://orcid.org/0000-0002-8109-5827","observed_orcids":["https://orcid.org/0000-0002-8109-5827"]},"institutions":[{"id":"https://openalex.org/I4210097509","display_name":"Second Affiliated Hospital of Chongqing Medical University","ror":"https://ror.org/00r67fz39","country_code":"CN","type":"healthcare","lineage":["https://openalex.org/I4210097509"]},{"id":"https://openalex.org/I4210160019","display_name":"Chongqing Municipal Health Commission","ror":"https://ror.org/04ce5fg13","country_code":"CN","type":"government","lineage":["https://openalex.org/I4210157972","https://openalex.org/I4210160019"]}],"countries":["CN"],"is_corresponding":true,"raw_author_name":"Wang Deng","raw_affiliation_strings":["Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Chongqing Medical University","Key Laboratory of Respiratory Inflammatory Injury and Precision Diagnosis and Treatment, Chongqing municipal health and Health Committee"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Chongqing Medical University","institution_ids":["https://openalex.org/I4210097509"]},{"raw_affiliation_string":"Key Laboratory of Respiratory Inflammatory Injury and Precision Diagnosis and Treatment, Chongqing municipal health and Health Committee","institution_ids":["https://openalex.org/I4210160019"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5056206602"],"corresponding_institution_ids":["https://openalex.org/I4210097509","https://openalex.org/I4210160019"],"apc_list":{"value":3150,"currency":"CHF","value_usd":3801},"apc_paid":{"value":3150,"currency":"CHF","value_usd":3801},"fwci":0.0,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":{"value":0.0,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"17","issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10322","display_name":"Respiratory Support and Mechanisms","score":0.7484999895095825,"subfield":{"id":"https://openalex.org/subfields/2740","display_name":"Pulmonary and Respiratory Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10322","display_name":"Respiratory Support and Mechanisms","score":0.7484999895095825,"subfield":{"id":"https://openalex.org/subfields/2740","display_name":"Pulmonary and Respiratory Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10724","display_name":"Ion Transport and Channel Regulation","score":0.21279999613761902,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10549","display_name":"Neonatal Respiratory Health Research","score":0.009800000116229057,"subfield":{"id":"https://openalex.org/subfields/2740","display_name":"Pulmonary and Respiratory Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[],"concepts":[{"id":"https://openalex.org/C2777961210","wikidata":"https://www.wikidata.org/wiki/Q927148","display_name":"Bronchoalveolar lavage","level":3,"score":0.8098999857902527},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.5967000126838684},{"id":"https://openalex.org/C2778690821","wikidata":"https://www.wikidata.org/wiki/Q212354","display_name":"Cytokine","level":2,"score":0.5769000053405762},{"id":"https://openalex.org/C2777714996","wikidata":"https://www.wikidata.org/wiki/Q7886","display_name":"Lung","level":2,"score":0.5522000193595886},{"id":"https://openalex.org/C2778754761","wikidata":"https://www.wikidata.org/wiki/Q421804","display_name":"Lipopolysaccharide","level":2,"score":0.4702000021934509},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.4668999910354614},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.45010000467300415},{"id":"https://openalex.org/C86554907","wikidata":"https://www.wikidata.org/wiki/Q285613","display_name":"PI3K/AKT/mTOR pathway","level":3,"score":0.42480000853538513},{"id":"https://openalex.org/C127561419","wikidata":"https://www.wikidata.org/wiki/Q224527","display_name":"Downregulation and upregulation","level":3,"score":0.41110000014305115},{"id":"https://openalex.org/C81729549","wikidata":"https://www.wikidata.org/wiki/Q4649475","display_name":"A549 cell","level":3,"score":0.3874000012874603},{"id":"https://openalex.org/C2776914184","wikidata":"https://www.wikidata.org/wiki/Q101991","display_name":"Inflammation","level":2,"score":0.38589999079704285},{"id":"https://openalex.org/C171958077","wikidata":"https://www.wikidata.org/wiki/Q419333","display_name":"STAT protein","level":4,"score":0.375900000333786},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.3671000003814697},{"id":"https://openalex.org/C202751555","wikidata":"https://www.wikidata.org/wiki/Q221681","display_name":"In vitro","level":2,"score":0.36559998989105225},{"id":"https://openalex.org/C164027704","wikidata":"https://www.wikidata.org/wiki/Q3491837","display_name":"Proinflammatory cytokine","level":3,"score":0.3628999888896942},{"id":"https://openalex.org/C207001950","wikidata":"https://www.wikidata.org/wiki/Q141124","display_name":"In vivo","level":2,"score":0.35499998927116394},{"id":"https://openalex.org/C190283241","wikidata":"https://www.wikidata.org/wiki/Q14599311","display_name":"Apoptosis","level":2,"score":0.350600004196167},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.3375000059604645},{"id":"https://openalex.org/C13373296","wikidata":"https://www.wikidata.org/wiki/Q421866","display_name":"Chemokine","level":3,"score":0.301800012588501},{"id":"https://openalex.org/C6507245","wikidata":"https://www.wikidata.org/wiki/Q424948","display_name":"Epithelial sodium channel","level":3,"score":0.2985999882221222},{"id":"https://openalex.org/C2779854577","wikidata":"https://www.wikidata.org/wiki/Q191341","display_name":"Alveolar cells","level":3,"score":0.2863999903202057},{"id":"https://openalex.org/C88045685","wikidata":"https://www.wikidata.org/wiki/Q174576","display_name":"Activator (genetics)","level":3,"score":0.28130000829696655},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.2791999876499176},{"id":"https://openalex.org/C2776415932","wikidata":"https://www.wikidata.org/wiki/Q48743","display_name":"Western blot","level":3,"score":0.2703999876976013},{"id":"https://openalex.org/C205260736","wikidata":"https://www.wikidata.org/wiki/Q418939","display_name":"Heat shock protein","level":3,"score":0.2678000032901764},{"id":"https://openalex.org/C2778012055","wikidata":"https://www.wikidata.org/wiki/Q448687","display_name":"Alveolar macrophage","level":4,"score":0.26170000433921814},{"id":"https://openalex.org/C14077384","wikidata":"https://www.wikidata.org/wiki/Q18033186","display_name":"Suppressor of cytokine signaling 1","level":4,"score":0.2538999915122986},{"id":"https://openalex.org/C75217442","wikidata":"https://www.wikidata.org/wiki/Q423650","display_name":"Protein kinase B","level":3,"score":0.2533999979496002}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.3389/fimmu.2026.1947334","doi":"https://doi.org/10.3389/fimmu.2026.1947334","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fimmu.2026.1947334","pdf_url":"https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1947334/pdf","source":{"id":"https://openalex.org/S2595292759","display_name":"Frontiers in Immunology","issn_l":"1664-3224","issn":["1664-3224"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","jufo-1","ki-jl-1","medline","norway-1","oarl","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Immunology","raw_type":"journal-article"}],"best_oa_location":{"id":"doi:10.3389/fimmu.2026.1947334","doi":"https://doi.org/10.3389/fimmu.2026.1947334","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fimmu.2026.1947334","pdf_url":"https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1947334/pdf","source":{"id":"https://openalex.org/S2595292759","display_name":"Frontiers in Immunology","issn_l":"1664-3224","issn":["1664-3224"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","jufo-1","ki-jl-1","medline","norway-1","oarl","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Immunology","raw_type":"journal-article"},"sustainable_development_goals":[],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7225780911.pdf","grobid_xml":"https://content.openalex.org/works/W7225780911.grobid-xml"},"referenced_works_count":48,"referenced_works":["https://openalex.org/W1803784511","https://openalex.org/W1937357008","https://openalex.org/W1979178732","https://openalex.org/W1987587689","https://openalex.org/W1995846325","https://openalex.org/W1997733329","https://openalex.org/W2000084288","https://openalex.org/W2012329129","https://openalex.org/W2015721729","https://openalex.org/W2053075265","https://openalex.org/W2075430896","https://openalex.org/W2082911112","https://openalex.org/W2104835376","https://openalex.org/W2110707896","https://openalex.org/W2120583839","https://openalex.org/W2125817800","https://openalex.org/W2150910507","https://openalex.org/W2156876013","https://openalex.org/W2170355978","https://openalex.org/W2208098683","https://openalex.org/W2589136587","https://openalex.org/W2848678871","https://openalex.org/W2945654734","https://openalex.org/W2980250057","https://openalex.org/W2985739961","https://openalex.org/W3035217157","https://openalex.org/W3190662999","https://openalex.org/W3204170184","https://openalex.org/W4205485543","https://openalex.org/W4205735962","https://openalex.org/W4221008539","https://openalex.org/W4224019015","https://openalex.org/W4226087560","https://openalex.org/W4283447161","https://openalex.org/W4294767945","https://openalex.org/W4294767986","https://openalex.org/W4317748817","https://openalex.org/W4366985566","https://openalex.org/W4386910704","https://openalex.org/W4388413833","https://openalex.org/W4388750408","https://openalex.org/W4388789710","https://openalex.org/W4400078469","https://openalex.org/W4400542390","https://openalex.org/W4400856176","https://openalex.org/W4403828429","https://openalex.org/W4417260091","https://openalex.org/W7143325084"],"related_works":[],"abstract_inverted_index":{"Introduction":[0],"Impaired":[1],"alveolar":[2,251],"fluid":[3,146,252],"clearance":[4,253],"(AFC)":[5],"is":[6,57],"a":[7,38,259],"major":[8],"pathological":[9],"feature":[10],"of":[11,61,74,133,264],"acute":[12],"lung":[13,140,190,193],"injury":[14,191],"(ALI).":[15],"The":[16,131],"epithelial":[17],"sodium":[18],"channel":[19],"(ENaC)":[20],"and":[21,72,100,150,155,169,171,201,209,221,235,254],"Na":[22,156,210,222],"+":[23,25,157,159,211,213,223,225],"/K":[24,158,212,224],"-ATPase":[26,160,214,226],"are":[27],"the":[28,70,127,231,265],"principal":[29],"ion":[30],"transport":[31],"proteins":[32],"that":[33,248,269],"mediate":[34],"AFC.":[35],"Isthmin-1":[36],"(ISM1),":[37],"secreted":[39],"protein":[40,148,199],"with":[41,120,206],"diverse":[42],"biological":[43],"functions,":[44],"has":[45],"been":[46],"reported":[47],"to":[48,68,107],"protect":[49],"against":[50,256,275],"ALI;":[51],"however,":[52],"whether":[53],"this":[54],"protective":[55,273],"effect":[56],"mediated":[58],"through":[59,258],"modulation":[60],"AFC":[62,78],"remains":[63],"unknown.":[64],"This":[65],"study":[66],"aimed":[67],"elucidate":[69],"role":[71],"mechanism":[73,261],"ISM1":[75,87,122,181,218,249,270],"in":[76,79,90,177],"regulating":[77],"lipopolysaccharide":[80],"(LPS)-induced":[81],"ALI.":[82,276],"Methods":[83],"In":[84,112],"vivo":[85],",":[86,114],"was":[88,105,135,175],"overexpressed":[89],"mice":[91],"using":[92],"an":[93,101],"adeno-associated":[94],"virus":[95],"serotype":[96],"5":[97],"(AAV5)":[98],"vector,":[99],"anti-GRP78":[102,124],"blocking":[103],"antibody":[104],"administered":[106],"neutralize":[108],"cell-surface":[109],"GRP78":[110,242],"function.":[111],"vitro":[113],"LPS-stimulated":[115],"A549":[116],"cells":[117],"were":[118,163,238],"treated":[119],"recombinant":[121],"protein,":[123],"antibody,":[125],"or":[126],"PI3K":[128],"activator":[129],"740Y-P.":[130],"severity":[132],"ALI":[134,257],"assessed":[136],"by":[137,165,188,229,241],"hematoxylin-eosin":[138],"staining,":[139],"wet/dry":[141,194],"weight":[142,195],"ratio,":[143],"bronchoalveolar":[144],"lavage":[145],"total":[147,198],"concentration,":[149],"inflammatory":[151,202],"cytokine":[152,203],"levels.":[153],"\u03b1-ENaC":[154,208,220],"\u03b11":[161,215,227],"expression":[162,228],"evaluated":[164],"Western":[166],"blot,":[167],"RT-qPCR,":[168],"immunofluorescence,":[170],"PI3K-AKT-mTOR":[172,232,266],"pathway":[173],"activity":[174],"analyzed":[176],"both":[178],"models.":[179],"Results":[180],"overexpression":[182],"attenuated":[183,240],"LPS-induced":[184],"ALI,":[185],"as":[186],"shown":[187],"reduced":[189],"scores,":[192],"ratios,":[196],"BALF":[197],"concentrations,":[200],"levels,":[204],"together":[205],"upregulated":[207],"expression.":[216],"Mechanistically,":[217],"promoted":[219],"suppressing":[230],"signaling":[233],"pathway,":[234,267],"these":[236],"effects":[237,274],"significantly":[239],"blockade.":[243],"Conclusions":[244],"These":[245],"findings":[246],"suggest":[247],"promotes":[250],"protects":[255],"GRP78-dependent":[260],"involving":[262],"inhibition":[263],"suggesting":[268],"may":[271],"have":[272]},"counts_by_year":[],"updated_date":"2026-11-12T12:28:57.059296","created_date":"2026-11-12T00:00:00"}
