Publication:
Histamine signaling and metabolism identify potential biomarkers and therapies for lymphangioleiomyomatosis.

dc.contributor.authorHerranz, Carmen
dc.contributor.authorMateo, Francesca
dc.contributor.authorBaiges, Alexandra
dc.contributor.authorRuiz-de-Garibay, Gorka
dc.contributor.authorJunza, Alexandra
dc.contributor.authorJohnson, Simon R
dc.contributor.authorMiller, Suzanne
dc.contributor.authorGarcia, Nadia
dc.contributor.authorCapellades, Jordi
dc.contributor.authorGomez, Antonio
dc.contributor.authorVidal, August
dc.contributor.authorPalomero, Luis
dc.contributor.authorEspín, Roderic
dc.contributor.authorExtremera, Ana I
dc.contributor.authorBlommaert, Eline
dc.contributor.authorRevilla-Lopez, Eva
dc.contributor.authorSaez, Berta
dc.contributor.authorGomez-Olles, Susana
dc.contributor.authorAncochea, Julio
dc.contributor.authorValenzuela, Claudia
dc.contributor.authorAlonso, Tamara
dc.contributor.authorUssetti, Piedad
dc.contributor.authorLaporta, Rosalia
dc.contributor.authorXaubet, Antoni
dc.contributor.authorRodriguez-Portal, Jose A
dc.contributor.authorMontes-Worboys, Ana
dc.contributor.authorMachahua, Carlos
dc.contributor.authorBordas, Jaume
dc.contributor.authorMenendez, Javier A
dc.contributor.authorCruzado, Josep M
dc.contributor.authorGuiteras, Roser
dc.contributor.authorBontoux, Christophe
dc.contributor.authorLa-Motta, Concettina
dc.contributor.authorNoguera-Castells, Aleix
dc.contributor.authorMancino, Mario
dc.contributor.authorLastra, Enrique
dc.contributor.authorRigo-Bonnin, Raul
dc.contributor.authorPerales, Jose C
dc.contributor.authorViñals, Francesc
dc.contributor.authorLahiguera, Alvaro
dc.contributor.authorZhang, Xiaohu
dc.contributor.authorCuadras, Daniel
dc.contributor.authorvan-Moorsel, Coline H M
dc.contributor.authorvan-der-Vis, Joanne J
dc.contributor.authorQuanjel, Marian J R
dc.contributor.authorFilippakis, Harilaos
dc.contributor.authorHakem, Razq
dc.contributor.authorGorrini, Chiara
dc.contributor.authorFerrer, Marc
dc.contributor.authorUgun-Klusek, Aslihan
dc.contributor.authorBillett, Ellen
dc.contributor.authorRadzikowska, Elżbieta
dc.contributor.authorCasanova, Alvaro
dc.contributor.authorMolina-Molina, Maria
dc.contributor.authorRoman, Antonio
dc.contributor.authorYanes, Oscar
dc.contributor.authorPujana, Miquel A
dc.contributor.funderInstituto de Salud Carlos III
dc.contributor.funderGeneralitat de Catalunya
dc.date.accessioned2023-02-12T02:34:44Z
dc.date.available2023-02-12T02:34:44Z
dc.date.issued2021-08-11
dc.description.abstractInhibition of mTOR is the standard of care for lymphangioleiomyomatosis (LAM). However, this therapy has variable tolerability and some patients show progressive decline of lung function despite treatment. LAM diagnosis and monitoring can also be challenging due to the heterogeneity of symptoms and insufficiency of non-invasive tests. Here, we propose monoamine-derived biomarkers that provide preclinical evidence for novel therapeutic approaches. The major histamine-derived metabolite methylimidazoleacetic acid (MIAA) is relatively more abundant in LAM plasma, and MIAA values are independent of VEGF-D. Higher levels of histamine are associated with poorer lung function and greater disease burden. Molecular and cellular analyses, and metabolic profiling confirmed active histamine signaling and metabolism. LAM tumorigenesis is reduced using approved drugs targeting monoamine oxidases A/B (clorgyline and rasagiline) or histamine H1 receptor (loratadine), and loratadine synergizes with rapamycin. Depletion of Maoa or Hrh1 expression, and administration of an L-histidine analog, or a low L-histidine diet, also reduce LAM tumorigenesis. These findings extend our knowledge of LAM biology and suggest possible ways of improving disease management.
dc.description.versionSi
dc.identifier.citationHerranz C, Mateo F, Baiges A, Ruiz de Garibay G, Junza A, Johnson SR, et al. Histamine signaling and metabolism identify potential biomarkers and therapies for lymphangioleiomyomatosis. EMBO Mol Med. 2021 Sep 7;13(9):e13929.
dc.identifier.doi10.15252/emmm.202113929
dc.identifier.essn1757-4684
dc.identifier.pmcPMC8422079
dc.identifier.pmid34378323
dc.identifier.pubmedURLhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422079/pdf
dc.identifier.unpaywallURLhttp://diposit.ub.edu/dspace/bitstream/2445/179910/1/emmm.202113929.pdf
dc.identifier.urihttp://hdl.handle.net/10668/19505
dc.issue.number9
dc.journal.titleEMBO molecular medicine
dc.journal.titleabbreviationEMBO Mol Med
dc.language.isoen
dc.organizationInstituto de Biomedicina de Sevilla-IBIS
dc.organizationHospital Universitario Virgen del Rocío
dc.page.number21
dc.provenanceRealizada la curación de contenido 28/05/2025.
dc.publisherEMBO Press
dc.pubmedtypeJournal Article
dc.pubmedtypeResearch Support, Non-U.S. Gov't
dc.relation.projectIDPI15/00854
dc.relation.projectIDPI18/01029
dc.relation.projectIDICI19/00047
dc.relation.projectID2014‐364
dc.relation.projectID2017‐449
dc.relation.publisherversionhttps://doi.org/10.15252/emmm.202113929
dc.rightsAttribution 4.0 International
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectbiomarker
dc.subjecthistamine
dc.subjectlymphangioleiomyomatosis
dc.subjectmTOR
dc.subjecttherapy
dc.subject.decsHistamina
dc.subject.decsMetabolismo
dc.subject.decsOxidorreductasas
dc.subject.decsLinfangioleiomiomatosis
dc.subject.decsDiagnóstico
dc.subject.decsBiomarcadores
dc.subject.meshBiomarkers
dc.subject.meshHistamine
dc.subject.meshHumans
dc.subject.meshLung Neoplasms
dc.subject.meshLymphangioleiomyomatosis
dc.subject.meshSignal Transduction
dc.titleHistamine signaling and metabolism identify potential biomarkers and therapies for lymphangioleiomyomatosis.
dc.typeresearch article
dc.type.hasVersionVoR
dc.volume.number13
dspace.entity.typePublication

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