Histamine signaling and metabolism identify potential biomarkers and therapies for lymphangioleiomyomatosis
Mostra el registre complet Registre parcial de l'ítem
- dc.contributor.author Herranz Ors, Carmen, 1992-
- dc.contributor.author Gómez Moruno, Antonio
- dc.contributor.author Pujana, Miguel Angel
- dc.date.accessioned 2021-12-13T10:48:03Z
- dc.date.available 2021-12-13T10:48:03Z
- dc.date.issued 2021
- dc.description.abstract Inhibition 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.sponsorship This research was supported by AELAM, The LAM Foundation (Seed Grant 2019), Instituto de Salud Carlos III grants PI15/00854, PI18/01029, and ICI19/00047 (co-funded by European Regional Development Fund (ERDF), a way to build Europe), Generalitat de Catalunya SGR grants 2014-364 and 2017-449, the CERCA Program, and ZonMW-TopZorg grant 842002003. C.L.M. acknowledges the financial support (PRA-2017-51 project) of the University of Pisa. A.U.K. is supported by Nottingham Trent University’s Independent Fellowship Scheme
- dc.format.mimetype application/pdf
- dc.identifier.citation Herranz C, Mateo F, Baiges A, Ruíz 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. DOI: 10.15252/emmm.202113929
- dc.identifier.doi http://dx.doi.org/10.15252/emmm.202113929
- dc.identifier.issn 1757-4676
- dc.identifier.uri http://hdl.handle.net/10230/49179
- dc.language.iso eng
- dc.publisher EMBO Press
- dc.rights © 2021 Carmen Herranz et al. Published under the terms of the CC BY 4.0 license. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.other Limfoangiomiomatosi
- dc.subject.other Marcadors bioquímics
- dc.subject.other Histamina
- dc.subject.other Terapèutica
- dc.title Histamine signaling and metabolism identify potential biomarkers and therapies for lymphangioleiomyomatosis
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion