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Molecular Pathogenesis and Diagnostics of Lung Diseases
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Molecular Pathogenesis and Diagnostics of Lung Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 October 2024) | Viewed by 8152

Special Issue Editor

Dr. Amanda Iglesias

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Guest Editor
1. Instituto de Investigación Sanitaria Illes Balears (IdISBa), 07120 Palma de Mallorca, Spain
2. Centro de Investigación Biomédica en Red in Respiratory Diseases (CIBERES), 28029 Madrid, Spain
Interests: COPD; miRNAs; biomarker
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The study of the biological pathways underlying the pathogenesis of respiratory diseases (such as COPD, lung cancer, lung fibrosis, and asthma, among others) is one of the most relevant fields for biomedical research in respiratory medicine. This Special Issue aims to focus on the most recent advances and molecular discoveries of the pathways and processes involved in lung pathogenesis, which could serve as a basis for the development of potential therapies and diagnostic tools, such as predictor biomarkers (specially microRNAs and other molecules that can be found in liquid and tissue biopsies). Original research, as well as review articles, are welcome in this Special Issue, although cutting-edge methodologies might also be considered. The spread of such advances will provide the basis and standards for further research and the development of new diagnostic and therapeutic approaches.

Dr. Amanda Iglesias
Guest Editor

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Published Papers (5 papers)

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Research

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16 pages, 2873 KiB  
Article
Transcriptome Analysis of Fibroblasts in Hypoxia-Induced Vascular Remodeling: Functional Roles of CD26/DPP4
by Yuri Suzuki, Takeshi Kawasaki, Koichiro Tatsumi, Tadasu Okaya, Shun Sato, Ayako Shimada, Tomoko Misawa, Ryo Hatano, Chikao Morimoto, Yoshitoshi Kasuya, Yoshinori Hasegawa, Osamu Ohara and Takuji Suzuki
Int. J. Mol. Sci. 2024, 25(23), 12599; https://doi.org/10.3390/ijms252312599 - 23 Nov 2024
Viewed by 383
Abstract
In hypoxic pulmonary hypertension (PH), pulmonary vascular remodeling is characterized by the emergence of activated adventitial fibroblasts, leading to medial smooth muscle hyperplasia. Previous studies have suggested that CD26/dipeptidyl peptidase-4 (DPP4) plays a crucial role in the pathobiological processes in lung diseases. However, [...] Read more.
In hypoxic pulmonary hypertension (PH), pulmonary vascular remodeling is characterized by the emergence of activated adventitial fibroblasts, leading to medial smooth muscle hyperplasia. Previous studies have suggested that CD26/dipeptidyl peptidase-4 (DPP4) plays a crucial role in the pathobiological processes in lung diseases. However, its role in pulmonary fibroblasts in hypoxic PH remains unknown. Therefore, we aimed to clarify the mechanistic role of CD26/DPP4 in lung fibroblasts in hypoxic PH. Dpp4 knockout (Dpp4 KO) and wild-type (WT) mice were exposed to hypoxia for 4 weeks. The degree of PH severity and medial wall thickness was augmented in Dpp4 KO mice compared with that in WT mice, suggesting that CD26/DPP4 plays a suppressive role in the development of hypoxic PH. Transcriptome analysis of human lung fibroblasts cultured under hypoxic conditions revealed that TGFB2, TGFB3, and TGFA were all upregulated as differentially expressed genes after DPP4 knockdown with small interfering RNA treatment. These results suggest that CD26/DPP4 plays a suppressive role in TGFβ signal-regulated fibroblast activation under hypoxic conditions. Therefore, CD26/DPP4 may be a potential therapeutic target in patients with PH associated with chronic hypoxia. Full article
(This article belongs to the Special Issue Molecular Pathogenesis and Diagnostics of Lung Diseases)
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20 pages, 2432 KiB  
Article
Cardiopulmonary Complications after Pulmonary Embolism in COVID-19
by Carla Suarez-Castillejo, Néstor Calvo, Luminita Preda, Rocío Córdova Díaz, Nuria Toledo-Pons, Joaquín Martínez, Jaume Pons, Miquel Vives-Borràs, Pere Pericàs, Luisa Ramón, Amanda Iglesias, Laura Cànaves-Gómez, Jose Luis Valera Felices, Daniel Morell-García, Belén Núñez, Jaume Sauleda, Ernest Sala-Llinàs and Alberto Alonso-Fernández
Int. J. Mol. Sci. 2024, 25(13), 7270; https://doi.org/10.3390/ijms25137270 - 2 Jul 2024
Viewed by 1016
Abstract
Although pulmonary embolism (PE) is a frequent complication in COVID-19, its consequences remain unknown. We performed pulmonary function tests, echocardiography and computed tomography pulmonary angiography and identified blood biomarkers in a cohort of consecutive hospitalized COVID-19 patients with pneumonia to describe and compare [...] Read more.
Although pulmonary embolism (PE) is a frequent complication in COVID-19, its consequences remain unknown. We performed pulmonary function tests, echocardiography and computed tomography pulmonary angiography and identified blood biomarkers in a cohort of consecutive hospitalized COVID-19 patients with pneumonia to describe and compare medium-term outcomes according to the presence of PE, as well as to explore their potential predictors. A total of 141 patients (56 with PE) were followed up during a median of 6 months. Post-COVID-19 radiological lung abnormalities (PCRLA) and impaired diffusing capacity for carbon monoxide (DLCOc) were found in 55.2% and 67.6% cases, respectively. A total of 7.3% had PE, and 6.7% presented an intermediate–high probability of pulmonary hypertension. No significant difference was found between PE and non-PE patients. Univariate analysis showed that age > 65, some clinical severity factors, surfactant protein-D, baseline C-reactive protein, and both peak red cell distribution width and Interleukin (IL)-10 were associated with DLCOc < 80%. A score for PCRLA prediction including age > 65, minimum lymphocyte count, and IL-1β concentration on admission was constructed with excellent overall performance. In conclusion, reduced DLCOc and PCRLA were common in COVID-19 patients after hospital discharge, but PE did not increase the risk. A PCRLA predictive score was developed, which needs further validation. Full article
(This article belongs to the Special Issue Molecular Pathogenesis and Diagnostics of Lung Diseases)
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15 pages, 3242 KiB  
Article
Effect of Obstructive Sleep Apnea during Pregnancy on Fetal Development: Gene Expression Profile of Cord Blood
by Laura Cànaves-Gómez, Aarne Fleischer, Josep Muncunill-Farreny, María Paloma Gimenez, Ainhoa Álvarez Ruiz De Larrinaga, Andrés Sánchez Baron, Mercedes Codina Marcet, Mónica De-La-Peña, Daniel Morell-Garcia, José Peña Zarza, Concepción Piñas Zebrian, Susana García Fernández and Alberto Alonso
Int. J. Mol. Sci. 2024, 25(10), 5537; https://doi.org/10.3390/ijms25105537 - 19 May 2024
Viewed by 1226
Abstract
Obstructive sleep apnea (OSA) is quite prevalent during pregnancy and is associated with adverse perinatal outcomes, but its potential influence on fetal development remains unclear. This study investigated maternal OSA impact on the fetus by analyzing gene expression profiles in whole cord blood [...] Read more.
Obstructive sleep apnea (OSA) is quite prevalent during pregnancy and is associated with adverse perinatal outcomes, but its potential influence on fetal development remains unclear. This study investigated maternal OSA impact on the fetus by analyzing gene expression profiles in whole cord blood (WCB). Ten women in the third trimester of pregnancy were included, five OSA and five non-OSA cases. WCB RNA expression was analyzed by microarray technology to identify differentially expressed genes (DEGs) under OSA conditions. After data normalization, 3238 genes showed significant differential expression under OSA conditions, with 2690 upregulated genes and 548 downregulated genes. Functional enrichment was conducted using gene set enrichment analysis (GSEA) applied to Gene Ontology annotations. Key biological processes involved in OSA were identified, including response to oxidative stress and hypoxia, apoptosis, insulin response and secretion, and placental development. Moreover, DEGs were confirmed through qPCR analyses in additional WCB samples (7 with OSA and 13 without OSA). This highlighted differential expression of several genes in OSA (EGR1, PFN1 and PRKAR1A), with distinct gene expression profiles observed during rapid eye movement (REM)-OSA in pregnancy (PFN1, UBA52, EGR1, STX4, MYC, JUNB, and MAPKAP). These findings suggest that OSA, particularly during REM sleep, may negatively impact various biological processes during fetal development. Full article
(This article belongs to the Special Issue Molecular Pathogenesis and Diagnostics of Lung Diseases)
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Review

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28 pages, 1407 KiB  
Review
Extracellular Vesicle microRNA: A Promising Biomarker and Therapeutic Target for Respiratory Diseases
by Jiaxi Lv and Xianzhi Xiong
Int. J. Mol. Sci. 2024, 25(17), 9147; https://doi.org/10.3390/ijms25179147 - 23 Aug 2024
Viewed by 1370
Abstract
Respiratory diseases, including chronic obstructive pulmonary disease (COPD), asthma, lung cancer, and coronavirus pneumonia, present a major global health challenge. Current diagnostic and therapeutic options for these diseases are limited, necessitating the urgent development of novel biomarkers and therapeutic strategies. In recent years, [...] Read more.
Respiratory diseases, including chronic obstructive pulmonary disease (COPD), asthma, lung cancer, and coronavirus pneumonia, present a major global health challenge. Current diagnostic and therapeutic options for these diseases are limited, necessitating the urgent development of novel biomarkers and therapeutic strategies. In recent years, microRNAs (miRNAs) within extracellular vesicles (EVs) have received considerable attention due to their crucial role in intercellular communication and disease progression. EVs are membrane-bound structures released by cells into the extracellular environment, encapsulating a variety of biomolecules such as DNA, RNA, lipids, and proteins. Specifically, miRNAs within EVs, known as EV-miRNAs, facilitate intercellular communication by regulating gene expression. The expression levels of these miRNAs can reflect distinct disease states and significantly influence immune cell function, chronic airway inflammation, airway remodeling, cell proliferation, angiogenesis, epithelial-mesenchymal transition, and other pathological processes. Consequently, EV-miRNAs have a profound impact on the onset, progression, and therapeutic responses of respiratory diseases, with great potential for disease management. Synthesizing the current understanding of EV-miRNAs in respiratory diseases such as COPD, asthma, lung cancer, and novel coronavirus pneumonia, this review aims to explore the potential of EV-miRNAs as biomarkers and therapeutic targets and examine their prospects in the diagnosis and treatment of these respiratory diseases. Full article
(This article belongs to the Special Issue Molecular Pathogenesis and Diagnostics of Lung Diseases)
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12 pages, 3644 KiB  
Review
Vascular Endothelial Growth Factor as Molecular Target for Bronchopulmonary Dysplasia Prevention in Very Low Birth Weight Infants
by Serafina Perrone, Sara Manti, Luca Buttarelli, Chiara Petrolini, Giovanni Boscarino, Laura Filonzi, Eloisa Gitto, Susanna Maria Roberta Esposito and Francesco Nonnis Marzano
Int. J. Mol. Sci. 2023, 24(3), 2729; https://doi.org/10.3390/ijms24032729 - 1 Feb 2023
Cited by 11 | Viewed by 3256
Abstract
Bronchopulmonary dysplasia (BPD) still represents an important burden of neonatal care. The definition of the disease is currently undergoing several revisions, and, to date, BPD is actually defined by its treatment rather than diagnostic or clinic criteria. BPD is associated with many prenatal [...] Read more.
Bronchopulmonary dysplasia (BPD) still represents an important burden of neonatal care. The definition of the disease is currently undergoing several revisions, and, to date, BPD is actually defined by its treatment rather than diagnostic or clinic criteria. BPD is associated with many prenatal and postnatal risk factors, such as maternal smoking, chorioamnionitis, intrauterine growth restriction (IUGR), patent ductus arteriosus (PDA), parenteral nutrition, sepsis, and mechanical ventilation. Various experimental models have shown how these factors cause distorted alveolar and vascular growth, as well as alterations in the composition and differentiation of the mesenchymal cells of a newborn’s lungs, demonstrating a multifactorial pathogenesis of the disease. In addition, inflammation and oxidative stress are the common denominators of the mechanisms that contribute to BPD development. Vascular endothelial growth factor-A (VEGFA) constitutes the most prominent and best studied candidate for vascular development. Animal models have confirmed the important regulatory roles of epithelial-expressed VEGF in lung development and function. This educational review aims to discuss the inflammatory pathways in BPD onset for preterm newborns, focusing on the role of VEGFA and providing a summary of current and emerging evidence. Full article
(This article belongs to the Special Issue Molecular Pathogenesis and Diagnostics of Lung Diseases)
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