Articles producció científica> Enginyeria Electrònica, Elèctrica i Automàtica

Histamine signaling and metabolism identify potential biomarkers and therapies for lymphangioleiomyomatosis

  • Identification data

    Identifier: imarina:9226195
    Authors:
    Herranz, CarmenMateo, FrancescaBaiges, Alexandrade Garibay, Gorka RuizJunza, AlexandraJohnson, Simon RMiller, SuzanneGarcia, NadiaCapellades, JordiGomez, AntonioVidal, AugustPalomero, LuisEspin, RodericExtremera, Ana, IBlommaert, ElineRevilla-Lopez, EvaSaez, BertaGomez-Olles, SusanaAncochea, JulioValenzuela, ClaudiaAlonso, TamaraUssetti, PiedadLaporta, RosaliaXaubet, AntoniRodriguez-Portal, Jose AMontes-Worboys, AnaMachahua, CarlosBordas, JaumeMenendez, Javier ACruzado, Josep MGuiteras, RoserBontoux, ChristopheLa Motta, ConcettinaNoguera-Castells, AleixMancino, MarioLastra, EnriqueRigo-Bonnin, RaulPerales, Jose CVinals, FrancescLahiguera, AlvaroZhang, XiaohuCuadras, Danielvan Moorsel, Coline H Mvan der Vis, Joanne JQuanjel, Marian J RFilippakis, HarilaosHakem, RazqGorrini, ChiaraFerrer, MarcUgun-Klusek, AslihanBillett, EllenRadzikowska, ElzbietaCasanova, AlvaroMolina-Molina, MariaRoman, AntonioYanes, OscarPujana, Miquel A
    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.
  • Others:

    Author, as appears in the article.: Herranz, Carmen; Mateo, Francesca; Baiges, Alexandra; de Garibay, Gorka Ruiz; Junza, Alexandra; Johnson, Simon R; Miller, Suzanne; Garcia, Nadia; Capellades, Jordi; Gomez, Antonio; Vidal, August; Palomero, Luis; Espin, Roderic; Extremera, Ana, I; Blommaert, Eline; Revilla-Lopez, Eva; Saez, Berta; Gomez-Olles, Susana; Ancochea, Julio; Valenzuela, Claudia; Alonso, Tamara; Ussetti, Piedad; Laporta, Rosalia; Xaubet, Antoni; Rodriguez-Portal, Jose A; Montes-Worboys, Ana; Machahua, Carlos; Bordas, Jaume; Menendez, Javier A; Cruzado, Josep M; Guiteras, Roser; Bontoux, Christophe; La Motta, Concettina; Noguera-Castells, Aleix; Mancino, Mario; Lastra, Enrique; Rigo-Bonnin, Raul; Perales, Jose C; Vinals, Francesc; Lahiguera, Alvaro; Zhang, Xiaohu; Cuadras, Daniel; van Moorsel, Coline H M; van der Vis, Joanne J; Quanjel, Marian J R; Filippakis, Harilaos; Hakem, Razq; Gorrini, Chiara; Ferrer, Marc; Ugun-Klusek, Aslihan; Billett, Ellen; Radzikowska, Elzbieta; Casanova, Alvaro; Molina-Molina, Maria; Roman, Antonio; Yanes, Oscar; Pujana, Miquel A
    Department: Enginyeria Electrònica, Elèctrica i Automàtica
    URV's Author/s: Junza Martínez, Alexandra / Yanes Torrado, Óscar
    Keywords: Vasculotropin d Unclassified drug Tumor xenograft Tsc2 Therapy Sirolimus Signal transduction Rasagiline Rapamycin Protein expression level Protein expression Protein depletion Promotes P70 s6 kinase Nonhuman Mtor Mouse Monotherapy Molecular dynamics Methylimidazoleacetic acid Metastatic breast cancer Metastasis Metabolic fingerprinting Major clinical study Lymphangioleiomyomatosis Lung tumor Lung neoplasms Lung function Loratadine Imidazoleacetic acid Humans Human tissue Human Histopathology Histidine derivative Histamine metabolism Histamine h1 receptor Histamine Gene Female Enzyme activity Embryo Drug targeting Drug potentiation Disease burden Disease association Diet restriction Controlled study Cohort analysis Clorgyline Clinical feature Cells Carcinogenesis Cancer inhibition Breast-cancer Biomarkers Biomarker Biological marker Article Antitumorigenic activity Animal tissue Animal model Animal experiment Animal cell Amine oxidase (flavin containing) isoenzyme b Amine oxidase (flavin containing) isoenzyme a Adult Activation
    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.
    Thematic Areas: Molecular medicine Medicine, research & experimental Medicina veterinaria Medicina ii Medicina i Farmacia Ciências biológicas iii Ciências biológicas ii Ciências biológicas i
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    Author's mail: oscar.yanes@urv.cat alexandra.junza@urv.cat
    Author identifier: 0000-0003-3695-7157 0000-0001-7205-0419
    Record's date: 2024-10-12
    Papper version: info:eu-repo/semantics/publishedVersion
    Link to the original source: https://www.embopress.org/doi/full/10.15252/emmm.202113929
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Papper original source: Embo Molecular Medicine. 13 (9): e13929-
    APA: Herranz, Carmen; Mateo, Francesca; Baiges, Alexandra; de Garibay, Gorka Ruiz; Junza, Alexandra; Johnson, Simon R; Miller, Suzanne; Garcia, Nadia; Cape (2021). Histamine signaling and metabolism identify potential biomarkers and therapies for lymphangioleiomyomatosis. Embo Molecular Medicine, 13(9), e13929-. DOI: 10.15252/emmm.202113929
    Article's DOI: 10.15252/emmm.202113929
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2021
    Publication Type: Journal Publications
  • Keywords:

    Medicine, Research & Experimental,Molecular Medicine
    Vasculotropin d
    Unclassified drug
    Tumor xenograft
    Tsc2
    Therapy
    Sirolimus
    Signal transduction
    Rasagiline
    Rapamycin
    Protein expression level
    Protein expression
    Protein depletion
    Promotes
    P70 s6 kinase
    Nonhuman
    Mtor
    Mouse
    Monotherapy
    Molecular dynamics
    Methylimidazoleacetic acid
    Metastatic breast cancer
    Metastasis
    Metabolic fingerprinting
    Major clinical study
    Lymphangioleiomyomatosis
    Lung tumor
    Lung neoplasms
    Lung function
    Loratadine
    Imidazoleacetic acid
    Humans
    Human tissue
    Human
    Histopathology
    Histidine derivative
    Histamine metabolism
    Histamine h1 receptor
    Histamine
    Gene
    Female
    Enzyme activity
    Embryo
    Drug targeting
    Drug potentiation
    Disease burden
    Disease association
    Diet restriction
    Controlled study
    Cohort analysis
    Clorgyline
    Clinical feature
    Cells
    Carcinogenesis
    Cancer inhibition
    Breast-cancer
    Biomarkers
    Biomarker
    Biological marker
    Article
    Antitumorigenic activity
    Animal tissue
    Animal model
    Animal experiment
    Animal cell
    Amine oxidase (flavin containing) isoenzyme b
    Amine oxidase (flavin containing) isoenzyme a
    Adult
    Activation
    Molecular medicine
    Medicine, research & experimental
    Medicina veterinaria
    Medicina ii
    Medicina i
    Farmacia
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
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