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Article ; Online: Advances and Highlights of miRNAs in Asthma: Biomarkers for Diagnosis and Treatment.

Gil-Martínez, Marta / Lorente-Sorolla, Clara / Naharro, Sara / Rodrigo-Muñoz, José M / Del Pozo, Victoria

International journal of molecular sciences

2023 Volume 24, Issue 2

Abstract: Asthma is a heterogeneous inflammatory disease of the airways that causes breathing difficulties, episodes of cough and wheezing, and in more severe cases can greatly diminish quality of life. Epigenetic regulation, including post-transcriptional ... ...

Abstract	Asthma is a heterogeneous inflammatory disease of the airways that causes breathing difficulties, episodes of cough and wheezing, and in more severe cases can greatly diminish quality of life. Epigenetic regulation, including post-transcriptional mediation of microRNAs (miRNAs), is one of the mechanisms behind the development of the range of asthma phenotypes and endotypes. As in every other immune-mediated disease, miRNAs regulate the behavior of cells that shape the airway structure as well as those in charge of the defense mechanisms in the bronchi and lungs, controlling cell survival, growth, proliferation, and the ability of cells to synthesize and secrete chemokines and immune mediators. More importantly, miRNAs are molecules with chemical and biological properties that make them appropriate biomarkers for disease, enabling stratification of patients for optimal drug selection and thereby simplifying clinical management and reducing both the economic burden and need for critical care associated with the disease. In this review, we summarize the roles of miRNAs in asthma and describe how they regulate the mechanisms of the disease. We further describe the current state of miRNAs as biomarkers for asthma phenotyping, endotyping, and treatment selection.
MeSH term(s)	Humans ; MicroRNAs/genetics ; Epigenesis, Genetic ; Quality of Life ; Asthma/diagnosis ; Asthma/drug therapy ; Asthma/genetics ; Biomarkers
Chemical Substances	MicroRNAs ; Biomarkers
Language	English
Publishing date	2023-01-13
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24021628
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Article ; Online: Exosomes: A Key Piece in Asthmatic Inflammation.

Cañas, José A / Rodrigo-Muñoz, José M / Gil-Martínez, Marta / Sastre, Beatriz / del Pozo, Victoria

International journal of molecular sciences

2021 Volume 22, Issue 2

Abstract: Asthma is a chronic disease of the airways that has an important inflammatory component. Multiple cells are implicated in asthma pathogenesis (lymphocytes, eosinophils, mast cells, basophils, neutrophils), releasing a wide variety of cytokines. These ... ...

Abstract	Asthma is a chronic disease of the airways that has an important inflammatory component. Multiple cells are implicated in asthma pathogenesis (lymphocytes, eosinophils, mast cells, basophils, neutrophils), releasing a wide variety of cytokines. These cells can exert their inflammatory functions throughout extracellular vesicles (EVs), which are small vesicles released by donor cells into the extracellular microenvironment that can be taken up by recipient cells. Depending on their size, EVs can be classified as microvesicles, exosomes, or apoptotic bodies. EVs are heterogeneous spherical structures secreted by almost all cell types. One of their main functions is to act as transporters of a wide range of molecules, such as proteins, lipids, and microRNAs (miRNAs), which are single-stranded RNAs of approximately 22 nucleotides in length. Therefore, exosomes could influence several physiological and pathological processes, including those involved in asthma. They can be detected in multiple cell types and biofluids, providing a wealth of information about the processes that take account in a pathological scenario. This review thus summarizes the most recent insights concerning the role of exosomes from different sources (several cell populations and biofluids) in one of the most prevalent respiratory diseases, asthma.
MeSH term(s)	Animals ; Asthma/etiology ; Asthma/pathology ; Cell Communication/physiology ; Cell-Derived Microparticles/metabolism ; Exosomes/pathology ; Exosomes/physiology ; Humans ; Inflammation/etiology ; Inflammation/pathology ; Secretory Vesicles/pathology ; Secretory Vesicles/physiology
Language	English
Publishing date	2021-01-19
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22020963
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Article ; Online: Emerging Evidence for Pleiotropism of Eosinophils.

Rodrigo-Muñoz, José M / Gil-Martínez, Marta / Sastre, Beatriz / Del Pozo, Victoria

International journal of molecular sciences

2021 Volume 22, Issue 13

Abstract: Eosinophils are complex granulocytes with the capacity to react upon diverse stimuli due to their numerous and variable surface receptors, which allows them to respond in very different manners. Traditionally believed to be only part of parasitic and ... ...

Abstract	Eosinophils are complex granulocytes with the capacity to react upon diverse stimuli due to their numerous and variable surface receptors, which allows them to respond in very different manners. Traditionally believed to be only part of parasitic and allergic/asthmatic immune responses, as scientific studies arise, the paradigm about these cells is continuously changing, adding layers of complexity to their roles in homeostasis and disease. Developing principally in the bone marrow by the action of IL-5 and granulocyte macrophage colony-stimulating factor GM-CSF, eosinophils migrate from the blood to very different organs, performing multiple functions in tissue homeostasis as in the gastrointestinal tract, thymus, uterus, mammary glands, liver, and skeletal muscle. In organs such as the lungs and gastrointestinal tract, eosinophils are able to act as immune regulatory cells and also to perform direct actions against parasites, and bacteria, where novel mechanisms of immune defense as extracellular DNA traps are key factors. Besides, eosinophils, are of importance in an effective response against viral pathogens by their nuclease enzymatic activity and have been lately described as involved in severe acute respiratory syndrome coronavirus SARS-CoV-2 immunity. The pleiotropic role of eosinophils is sustained because eosinophils can be also detrimental to human physiology, for example, in diseases like allergies, asthma, and eosinophilic esophagitis, where exosomes can be significant pathophysiologic units. These eosinophilic pathologies, require specific treatments by eosinophils control, such as new monoclonal antibodies like mepolizumab, reslizumab, and benralizumab. In this review, we describe the roles of eosinophils as effectors and regulatory cells and their involvement in pathological disorders and treatment.
MeSH term(s)	Antibodies, Monoclonal/therapeutic use ; Asthma/drug therapy ; Asthma/immunology ; Asthma/pathology ; COVID-19/immunology ; COVID-19/pathology ; COVID-19/virology ; Eosinophilic Esophagitis/drug therapy ; Eosinophilic Esophagitis/immunology ; Eosinophilic Esophagitis/pathology ; Eosinophils/cytology ; Eosinophils/immunology ; Eosinophils/physiology ; Exosomes/metabolism ; Extracellular Traps/metabolism ; Humans ; Plasma Cells/cytology ; Plasma Cells/metabolism ; SARS-CoV-2/isolation & purification
Chemical Substances	Antibodies, Monoclonal
Language	English
Publishing date	2021-06-30
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22137075
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Article ; Online: Corrigendum: MicroRNAs as potential regulators of immune response networks in asthma and chronic obstructive pulmonary disease.

Cañas, José A / Rodrigo-Muñoz, José M / Sastre, Beatriz / Gil-Martinez, Marta / Redondo, Natalia / Del Pozo, Victoria

Frontiers in immunology

2022 Volume 13, Page(s) 1051260

Abstract: This corrects the article DOI: 10.3389/fimmu.2020.608666.]. ...

Abstract	[This corrects the article DOI: 10.3389/fimmu.2020.608666.].
Language	English
Publishing date	2022-10-13
Publishing country	Switzerland
Document type	Published Erratum
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.1051260
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Article ; Online: Trace elements and C and N isotope composition in two mushroom species from a mine-spill contaminated site.

Gil-Martínez, Marta / Navarro-Fernández, Carmen M / Murillo, José M / Domínguez, María T / Marañón, Teodoro

Scientific reports

2020 Volume 10, Issue 1, Page(s) 6434

Abstract: Fungi play a key role in the functioning of soil in terrestrial ecosystems, and in particular in the remediation of degraded soils. The contribution of fungi to carbon and nutrient cycles, along with their capability to mobilise soil trace elements, is ... ...

Abstract	Fungi play a key role in the functioning of soil in terrestrial ecosystems, and in particular in the remediation of degraded soils. The contribution of fungi to carbon and nutrient cycles, along with their capability to mobilise soil trace elements, is well-known. However, the importance of life history strategy for these functions has not yet been thoroughly studied. This study explored the soil-fungi relationship of two wild edible fungi, the ectomycorrhizal Laccaria laccata and the saprotroph Volvopluteus gloiocephalus. Fruiting bodies and surrounding soils in a mine-spill contaminated area were analysed. Isotope analyses revealed Laccaria laccata fruiting bodies were
MeSH term(s)	Agaricales/chemistry ; Agaricales/metabolism ; Bioaccumulation ; Cadmium/analysis ; Cadmium/metabolism ; Cadmium/toxicity ; Carbon Isotopes/analysis ; Carbon Isotopes/metabolism ; Copper/analysis ; Copper/metabolism ; Copper/toxicity ; Environmental Monitoring ; Fruiting Bodies, Fungal/chemistry ; Fruiting Bodies, Fungal/metabolism ; Humans ; Mining ; Mushroom Poisoning/prevention & control ; Nitrogen Isotopes/analysis ; Nitrogen Isotopes/metabolism ; Soil/chemistry ; Soil Pollutants/analysis ; Soil Pollutants/metabolism ; Soil Pollutants/toxicity ; Trace Elements/analysis ; Trace Elements/metabolism ; Trace Elements/toxicity
Chemical Substances	Carbon Isotopes ; Nitrogen Isotopes ; Nitrogen-15 ; Soil ; Soil Pollutants ; Trace Elements ; Cadmium (00BH33GNGH) ; Copper (789U1901C5) ; Carbon-13 (FDJ0A8596D)
Language	English
Publishing date	2020-04-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-63194-2
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Article ; Online: Obese Asthma Phenotype Is Associated with hsa-miR-26a-1-3p and hsa-miR-376a-3p Modulating the IGF Axis.

Gil-Martínez, Marta / Lorente-Sorolla, Clara / Rodrigo-Muñoz, José M / Naharro, Sara / García-de Castro, Zahara / Sastre, Joaquín / Valverde-Monge, Marcela / Quirce, Santiago / Caballero, María L / Olaguibel, José M / Del Pozo, Victoria

International journal of molecular sciences

2023 Volume 24, Issue 14

Abstract: Clarifying inflammatory processes and categorising asthma into phenotypes and endotypes improves asthma management. Obesity worsens severe asthma and reduces quality of life, although its specific molecular impact remains unclear. We previously ... ...

Abstract	Clarifying inflammatory processes and categorising asthma into phenotypes and endotypes improves asthma management. Obesity worsens severe asthma and reduces quality of life, although its specific molecular impact remains unclear. We previously demonstrated that hsa-miR-26a-1-3p and hsa-miR-376a-3p, biomarkers related to an inflammatory profile, discriminate eosinophilic from non-eosinophilic asthmatics. We aimed to study hsa-miR-26a-1-3p, hsa-miR-376a-3p, and their target genes in asthmatic subjects with or without obesity to find biomarkers and comprehend obese asthma mechanisms. Lung tissue samples were obtained from asthmatic patients (n = 16) and healthy subjects (n = 20). We measured miRNA expression using RT-qPCR and protein levels (IGF axis) by ELISA in confirmation samples from eosinophilic (n = 38) and non-eosinophilic (n = 39) obese (n = 26) and non-obese (n = 51) asthma patients. Asthmatic lungs showed higher hsa-miR-26a-1-3p and hsa-miR-376a-3p expression than healthy lungs. A study of seven genes regulated by these miRNAs revealed differential expression of
MeSH term(s)	Humans ; Asthma/complications ; Asthma/genetics ; Biomarkers ; Insulin-Like Growth Factor Binding Protein 3/genetics ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Obesity/complications ; Obesity/genetics ; Phenotype ; Quality of Life
Chemical Substances	Biomarkers ; Insulin-Like Growth Factor Binding Protein 3 ; MicroRNAs ; MIRN376A1 microRNA, human
Language	English
Publishing date	2023-07-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241411620
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Article ; Online: MicroRNAs as Potential Regulators of Immune Response Networks in Asthma and Chronic Obstructive Pulmonary Disease.

Cañas, José A / Rodrigo-Muñoz, José M / Sastre, Beatriz / Gil-Martinez, Marta / Redondo, Natalia / Del Pozo, Victoria

Frontiers in immunology

2021 Volume 11, Page(s) 608666

Abstract: Chronic respiratory diseases (CRDs) are an important factor of morbidity and mortality, accounting for approximately 6% of total deaths worldwide. The main CRDs are asthma and chronic obstructive pulmonary disease (COPD). These complex diseases have ... ...

Abstract	Chronic respiratory diseases (CRDs) are an important factor of morbidity and mortality, accounting for approximately 6% of total deaths worldwide. The main CRDs are asthma and chronic obstructive pulmonary disease (COPD). These complex diseases have different triggers including allergens, pollutants, tobacco smoke, and other risk factors. It is important to highlight that although CRDs are incurable, various forms of treatment improve shortness of breath and quality of life. The search for tools that can ensure accurate diagnosis and treatment is crucial. MicroRNAs (miRNAs) are small non-coding RNAs and have been described as promising diagnostic and therapeutic biomarkers for CRDs. They are implicated in multiple processes of asthma and COPD, regulating pathways associated with inflammation, thereby showing that miRNAs are critical regulators of the immune response. Indeed, miRNAs have been found to be deregulated in several biofluids (sputum, bronchoalveolar lavage, and serum) and in both structural lung and immune cells of patients in comparison to healthy subjects, showing their potential role as biomarkers. Also, miRNAs play a part in the development or termination of histopathological changes and comorbidities, revealing the complexity of miRNA regulation and opening up new treatment possibilities. Finally, miRNAs have been proposed as prognostic tools in response to both conventional and biologic treatments for asthma or COPD, and miRNA-based treatment has emerged as a potential approach for clinical intervention in these respiratory diseases; however, this field is still in development. The present review applies a systems biology approach to the understanding of miRNA regulatory networks in asthma and COPD, summarizing their roles in pathophysiology, diagnosis, and treatment.
MeSH term(s)	Animals ; Asthma/immunology ; Humans ; Immunity/immunology ; Inflammation/immunology ; Lung/immunology ; MicroRNAs/immunology ; Pulmonary Disease, Chronic Obstructive/immunology ; Sputum/immunology
Chemical Substances	MicroRNAs
Language	English
Publishing date	2021-01-08
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.608666
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Article ; Online: Role of miR-185-5p as modulator of periostin synthesis and smooth muscle contraction in asthma.

Rodrigo-Muñoz, José M / Cañas, José A / Sastre, Beatriz / Gil-Martínez, Marta / García Latorre, Raquel / Sastre, Joaquín / Del Pozo, Victoria

Journal of cellular physiology

2021 Volume 237, Issue 2, Page(s) 1498–1508

Abstract: Asthma is a chronic respiratory disease produced by an aberrant immune response that originates with breathing difficulties and cough, through airway remodeling. The above pathophysiological events of asthma emerge the regulators of effectors, like ... ...

Abstract	Asthma is a chronic respiratory disease produced by an aberrant immune response that originates with breathing difficulties and cough, through airway remodeling. The above pathophysiological events of asthma emerge the regulators of effectors, like epigenetics, which include microRNAs (miRNAs) who perform post-transcriptional regulation, controlling diverse pathways in respiratory diseases. The objective of the study was to determine how miR-185-5p regulates the secretion of periostin by airway structural cells, and smooth muscle cells contraction, both related to airway remodeling in asthma. We used miR-185-5p mimic and inhibitors in bronchial smooth muscle cells (BSMCs) and small airway epithelial cells (SAECs) from healthy subjects. Gene expression and protein levels of periostin (POSTN), CDC42, and RHOA were analyzed by RT-PCR and ELISA/Western blot, respectively. BSMC contractility was analyzed using cell-embedded collagen gels and measurement of intracellular calcium was performed using Fura-2. Additionally, miR-185-5p and periostin expression were evaluated in sputum from healthy and asthmatics. From these experiments, we observed that miR-185-5p modulation regulates periostin mRNA and protein in BSMCs and SAECs. A tendency for diminished miR-185-5p expression and higher periostin levels was seen in sputum cells from asthmatics compared to healthy, with an inverse correlation observed between POSTN and miR-185-5p. Inhibition of miR-185-5p produced higher BSMCs contraction induced by histamine. Calcium mobilization was not modified by miR-185-5p, showing that miR-185-5p role in BSMC contractility is performed by regulating CDC42 and RhoA pro-contractile factors instead. In conclusion, miR-185-5p is a modulator of periostin secretion by airway structural cells and of smooth muscle contraction, which can be related to asthma pathophysiology, and thus, might be a promising therapeutic target.
MeSH term(s)	Airway Remodeling/genetics ; Asthma/metabolism ; Calcium/metabolism ; Cell Proliferation/genetics ; Humans ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Muscle Contraction/genetics ; Myocytes, Smooth Muscle/metabolism
Chemical Substances	MIRN185 microRNA, human ; MicroRNAs ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2021-10-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3116-1
ISSN	1097-4652 ; 0021-9541
ISSN (online)	1097-4652
ISSN	0021-9541
DOI	10.1002/jcp.30620
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Article: Variation in morphological and chemical traits of Mediterranean tree roots: linkage with leaf traits and soil conditions

Marañón, Teodoro / Navarro-Fernández, Carmen M / Gil-Martínez, Marta / Domínguez, María T / Madejón, Paula / Villar, Rafael

Plant and soil. 2020 Apr., v. 449, no. 1-2

2020

Abstract: AIMS: Root functions are multiple and essential for the growth and survival of terrestrial plants. The aim of this work was to analyse the main trends in the variation of root traits, their coordination with leaf traits and their relationships with soil ... ...

Abstract	AIMS: Root functions are multiple and essential for the growth and survival of terrestrial plants. The aim of this work was to analyse the main trends in the variation of root traits, their coordination with leaf traits and their relationships with soil conditions. METHODS: We measured the variation of 27 fine root traits (five morphological, 20 chemical and two isotopic signatures) in trees of seven species of a mixed plantation in a metal-contaminated and remediated site of Southern Spain. RESULTS: We found evidences supporting the existence of a root economics spectrum (RES). However, other dimensions were identified as being independent of the main RES: mainly the variation in the carbon concentration, the accumulation of trace elements associated with tolerance of metal-rich soils, and the fractionation of δ¹⁵N as a time-integrated trait of mycorrhizal-mediated nutrition. In general, roots and leaves were functionally coordinated, although most of the trace elements showed strong root-leaf discordance. The soil conditions interacted with the fine root traits in feedback processes. The ability of tree roots to accumulate trace elements and to reduce their translocation to leaves is a desirable trait for the phytoremediation of metal-contaminated soils. CONCLUSIONS: Roots are multifunctional. Understanding the variations in the root traits of trees will help us to predict both the responses of forests to global changes, including soil contamination, and the provision of soil-based ecosystem services.
Keywords	carbon ; ecosystems ; fine roots ; fractionation ; leaves ; nutrition ; phytoremediation ; soil pollution ; trees ; Spain
Language	English
Dates of publication	2020-04
Size	p. 389-403.
Publishing place	Springer International Publishing
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	208908-7
ISSN	1573-5036 ; 0032-079X
ISSN (online)	1573-5036
ISSN	0032-079X
DOI	10.1007/s11104-020-04485-5
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Article ; Online: Moderate-High Blood Eosinophilia Is Associated with Increased Hospitalization and Other Asthma Comorbidities.

Naharro-González, Sara / Lorente-Sorolla, Clara / Rodrigo-Muñoz, José Manuel / Valverde-Monge, Marcela / Pinillos-Robles, Erwin Javier / Betancor, Diana / Fernández-Nieto, Mar / Sánchez-Mellado, Diana / Gil-Martínez, Marta / Santillán-Coello, Jessica Mireya / Villacampa-Aubá, José Miguel / Mahillo-Fernandez, Ignacio / Herrero-González, Antonio / Perez-González, Alejandro / Rodríguez-Nieto, María Jesús / Del Pozo, Victoria

Biomolecules

2024 Volume 14, Issue 1

Abstract: 1) Background: Eosinophilia has traditionally been linked to eosinophilic asthma, for which it is the gold-standard prognostic biomarker. However, the association between eosinophilia and the presence of other diseases and comorbidities is yet unclear. ( ...

Abstract	(1) Background: Eosinophilia has traditionally been linked to eosinophilic asthma, for which it is the gold-standard prognostic biomarker. However, the association between eosinophilia and the presence of other diseases and comorbidities is yet unclear. (2) Methods: For this retrospective study, we reviewed the electronic medical records of 49,909 subjects with blood eosinophilia to gather data on the presence of asthma, COPD, sleep apnea, tuberculosis, dyslipidemia, hypertension, and other cardiovascular diseases and severe CRSwNP among these subjects. Demographic features including age, sex, and smoking habits were collected, as well as the number of hospitalizations and emergency department visits. T-tests, ANOVA, Fisher test, and logistic regression models were used. (3) Results: For all age groups studied, eosinophilia was significantly more prevalent among asthmatic subjects than nonasthmatics, especially in patients also presenting CRSwNP, hypertension, and dyslipidemia. The likelihood of developing asthma, COPD, and CRSwNP, and hospitalization, was increased when BEC was above 600 eosinophils/μL. The association between asthma, CRSwNP, and BEC was corroborated by multiple logistic regressions models. (4) Conclusions: We demonstrated the association of having over 600 blood eosinophils/μL with a higher number of hospitalizations and comorbidities (CRSwNP and COPD), which proves that BEC is a highly useful parameter to consider in subjects who present blood eosinophilia.
MeSH term(s)	Humans ; Animals ; Retrospective Studies ; Asthma/complications ; Asthma/epidemiology ; Hypertension ; Hospitalization ; Mustelidae ; Pulmonary Eosinophilia ; Dyslipidemias/epidemiology ; Pulmonary Disease, Chronic Obstructive/epidemiology
Language	English
Publishing date	2024-01-18
Publishing country	Switzerland
Document type	Review ; Journal Article
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom14010126
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