The Experts below are selected from a list of 127329 Experts worldwide ranked by ideXlab platform
Jorge Correia-pinto - One of the best experts on this subject based on the ideXlab platform.
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Retinoic Acid: A Key Regulator of Lung Development
Biomolecules, 2020Co-Authors: Hugo Fernandes-silva, Jorge Correia-pinto, Henrique Araújo-silva, Rute S. MouraAbstract:Retinoic acid (RA) is a key molecular player in embryogenesis and adult tissue homeostasis. In embryo Development, RA plays a crucial role in the formation of different organ systems, namely, the respiratory system. During Lung Development, there is a spatiotemporal regulation of RA levels that assures the formation of a fully functional organ. RA signaling influences Lung specification, branching morphogenesis, and alveolarization by regulating the expression of particular target genes. Moreover, cooperation with other Developmental pathways is essential to shape Lung organogenesis. This review focuses on the events regulated by retinoic acid during Lung Developmental phases and pulmonary vascular Development; also, it aims to provide a snapshot of RA interplay with other well-known regulators of Lung Development.
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Molecular Aspects of Avian Lung Development
The Biology of the Avian Respiratory System, 2017Co-Authors: Rute S. Moura, Jorge Correia-pintoAbstract:The pulmonary system develops from a series of complex events that involve coordinated growth and differentiation of distinct cellular compartments. After Lung specification of the anterior foregut endoderm, branching morphogenesis occurs generating an intricate arrangement of airways. This process depends on epithelial-mesenchymal interactions tightly controlled by a network of conserved signaling pathways. These signaling events regulate cellular processes and control the temporal-spatial expression of multiple molecular players that are essential for Lung formation. Additionally, remodeling of the extracellular matrix establishes the appropriate environment for the delivery of diffusible regulatory factors that modulate these cellular processes. In this chapter, the molecular mechanisms underlying avian Lung Development are thoroughly revised. Fibroblast growth factor, WNT, sonic hedgehog, transforming growth factor-β, bone morphogenetic protein, vascular endothelial growth factor, and regulatory mechanisms such as microRNAs control cell proliferation, differentiation, and patterning of the embryonic chick Lung. With this section, we aim to provide a snapshot of the current knowledge of the molecular aspects of avian Lung Development.
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THE ROLE OF JAK–STAT3 SIGNALLING PATHWAY DURING FETAL Lung Development
Archives of Disease in Childhood, 2008Co-Authors: Cristina Nogueira-silva, Rute S. Moura, Susana Nunes, Jorge Correia-pintoAbstract:Background and Aim The process of Lung Development involves several effectors that exert its action via the JAK/STAT signalling pathway. The elucidation of the signalling pathways involved in Lung Development may lead to strategies to rescue pulmonary hypoplasia associated with a broad spectrum of human diseases. Our aim was thus to clarify the role of STAT3 during fetal Lung Development. Materials and Methods The STAT3 expression pattern was assessed by immunohistochemistry. Rat Lung explants were harvested at 13.5 days postconception and cultured during 4 days with piceatannol, an inhibitor of STAT3 phosphorylation (0, 0.01, 0.1, 1, 10, 20, 30 ng/ml). STAT3, MAPK (ERK1/2, JNK and p38) and PI3-AKT phosphorylation in explants was assessed by Western blot. Morphometric analysis was performed in all Lung explants. Results STAT3 was expressed by pulmonary endothelium during Lung Development. Higher doses of piceatannol inhibited the JAK/STAT3 pathway and decreased Lung growth. However, lower doses of piceatannol induced an increase of STAT3 phosphorylation (accordingly previously described in the literature) and also increased Lung growth. Moreover, Western blot demonstrated no difference on ERK1/2, JNK, p38 and PI3-AKT pathways. Conclusions These findings suggest that the JAK/STAT3 signalling pathway is a positive regulator of fetal Lung Development. Moreover, the STAT3 endothelial expression proposes an airway–vasculature interaction on branching regulation.
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Ghrelin and obestatin: Different role in fetal Lung Development?
Peptides, 2008Co-Authors: Susana Nunes, Cristina Nogueira-silva, Rute S. Moura, Emanuel Dias, Jorge Correia-pintoAbstract:Ghrelin and obestatin are two proteins that originate from post-translational processing of the preproghrelin peptide. Various authors claim an opposed role of ghrelin and obestatin in several systems. Preproghrelin mRNA is significantly expressed in airway epithelium throughout Lung Development, predominantly during the earliest stages. The aim of this study was to evaluate the role of ghrelin and obestatin in fetal Lung Development in vitro. Immunohistochemistry studies were performed at different gestational ages in order to clarify the expression pattern of ghrelin, GHS-R1a, obestatin and GPR39 during fetal Lung Development. Fetal rat Lung explants were harvested at 13.5 days post-conception (dpc) and cultured during 4 days with increasing doses of total ghrelin, acylated ghrelin, desacyl-ghrelin, ghrelin antagonist (D-Lys(3)-GHRP-6) or obestatin. Immunohistochemistry studies demonstrated that ghrelin, GHS-R1a, obestatin and GPR39 proteins were expressed in primitive rat Lung epithelium throughout all studied gestational ages. Total and acylated ghrelin supplementation significantly increased the total number of peripheral airway buds, whereas desacyl-ghrelin induced no effect. Moreover, GHS-R1a antagonist significantly decreased Lung branching. Finally, obestatin supplementation induced no significant effect in the measured parameters. The present study showed that ghrelin has a positive effect in fetal Lung Development through its GHS-R1a receptor, whereas obestatin has no effect on Lung branching.
Martin Post - One of the best experts on this subject based on the ideXlab platform.
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Explant Culture for Studying Lung Development.
Methods in molecular biology (Clifton N.J.), 2018Co-Authors: Behzad Yeganeh, Claudia Bilodeau, Martin PostAbstract:Lung Development is a complex process that requires the input of various signaling pathways to coordinate the specification and differentiation of multiple cell types. Ex vivo culture of the Lung is a very useful technique that represents an attractive model for investigating many different processes critical to Lung Development, function, and disease pathology. Ex vivo cultured Lungs remain comparable to the in vivo Lung both in structure and function, which makes them more suitable than cell cultures for physiological studies. Lung explant cultures offer several significant advantages for studies of morphogenetic events that guide Lung Development including budding, branching, and fusion. It also maintains the native physiological interactions between cells in the developing Lung, enabling investigations of the direct and indirect signaling taking place between tissues and cells throughout the Developmental process. Studying temporal and spatial control of gene expression by transcriptional factors using different reporters to understand their regulatory function at different moments of Development is another valuable advantage of Lung explants culture.
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The molecular basis for abnormal human Lung Development.
Biology of the neonate, 2004Co-Authors: Frederick Groenman, Sharon Unger, Martin PostAbstract:Our understanding of Lung Development in the past two decades has moved from an anatomical to a histological basis and, most recently, to a molecular basis. Tissue interactions specify tracheal and Lung primordia formation, program branching morphogenesis of the airway epithelium and regulate epithelial differentiation. In addition, Lung Development is influenced by mechanical and humoral factors. The regulatory molecules involved in morphogenetic signaling include growth and transcription factors and extracellular matrix molecules. These morphogenetic signals are responsible for Lung patterning and differentiation. We will provide a brief overview of molecular signaling during early respiratory formation, airway branching, pulmonary vascularization and epithelial differentiation. We will then review aberrant morphogenetic signaling in human Lung abnormalities, such as tracheoesophageal fistula, congenital diaphragmatic hernia, pulmonary hyperplasia, alveolar capillary dysplasia, congenital cystic adenomatoid malformation and bronchopulmonary dysplasia.
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Apoptosis in Lung Development and Neonatal Lung Injury
Pediatric Research, 2004Co-Authors: Veronica Del Riccio, Minke Van Tuyl, Martin PostAbstract:A healthy organism maintains an integrated balance between proliferating, differentiating, and dying cells. Some cells are irreplaceable, some cells complete their functions and are then sacrificed, and some cells live a finite lifetime, to be replaced by another generation. Apoptosis is the last phase of a cell's destiny and a distinct form of programmed cell death. It is characterized by loss of cell function and rapid morphological changes, culminating in cell death without inflammation. Apoptosis has been found to play an important role in the normal regulation of organogenesis and morphogenesis during Development. Apoptosis is a fundamental feature in the Development of many tissue systems, including the immune and nervous systems, as well as in the Development of the kidneys and heart. The significance of apoptosis in Lung Development has been largely overlooked. Physical forces during Development may play a role in directing apoptosis in remodeling the Lung. This review summarizes current knowledge regarding apoptosis during Lung Development, with a particular emphasis on the potential role of mechanpotransduction as a stimulus for apoptosis.
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Overview of Lung Development
2003Co-Authors: Martin Post, Ian B. CoplandAbstract:Survival at birth depends on the adequate Development of the Lung in utero. Disorders of Lung growth, maturation and control of breathing continues to be some of the most important problems facing the neonatologist. Premature birth occurs in 5-10 % of all pregnancies, and one of the major complications with preterm birth is immaturity of the Lung. Despite modern management, many infants exhibit Lung dysfunction characterized by arrested Lung Development and interrupted alveolarization. This immature Lung phenotype, accounts for 75 % of early mortality and long-term disability in prematurely born infants. Infants that are most susceptible to Lung injury are typically extremely low-birth-weight (ELBW) infants, born between 24 and 28 weeks of gestation because their Lungs are delicate and have small gas exchange volumes. Over the past two decades molecular studies of Lung Development have started to shed light on the complex series of events that control proper formation of the Lung. Hopefully, a better understanding of the molecular basis of pulmonary Development will guide clinicians in the design of strategies to mimic normal Lung maturation in a premature infant. In this review we summarize the current thoughts on Lung Development, focusing on the molecular mechanisms controlling Lung growth and maturation up till birth.
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Shh/Gli Signalling during Murine Lung Development
Shh and Gli Signalling and Development, 1Co-Authors: Martin Rutter, Martin PostAbstract:Murine Lung Development is a complex process regulated by many factors guiding a carefully orchestrated series of events leading to mature Lung formation. Many Developmental pathways have been implicated in governing proper Lung formation. Most notably, the Shh/Gli pathway shown to be crucial to the Development of numerous other organ systems, is an absolute requirement for correct Lung formation. Many interactions between the Shh pathway and other fundamental Lung signalling molecules such as fibroblast growth factor 10 (Fgf10) have presented themselves. While the specifics of these interactions have yet to be elucidated, the consequence of their actions is paramount in guiding Lung Development.
Thomas J. Mariani - One of the best experts on this subject based on the ideXlab platform.
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Update on Molecular Biology of Lung Development—Transcriptomics
Clinics in perinatology, 2015Co-Authors: Thomas J. MarianiAbstract:This article highlights some of the significant advances in our understanding of Lung Developmental biology made over the last few years, which challenge existing paradigms and are relevant to a fundamental understanding of this process. Additional comments address how these new insights may be informative for chronic Lung diseases that occur, or initiate, in the neonatal period. This is not meant to be an exhaustive review of the molecular biology of Lung Development. For a more comprehensive, contemporary review of the cellular and molecular aspects of Lung Development, readers can refer to recent reviews by others.
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Transcriptomic Analysis of Human Lung Development
American journal of respiratory and critical care medicine, 2009Co-Authors: Alvin T. Kho, Soumyaroop Bhattacharya, Kelan G. Tantisira, Vincent J. Carey, Roger Gaedigk, J. Steven Leeder, Isaac S. Kohane, Scott T. Weiss, Thomas J. MarianiAbstract:Rationale: Current understanding of the molecular regulation of Lung Development is limited and derives mostly from animal studies.Objectives: To define global patterns of gene expression during human Lung Development.Methods: Genome-wide expression profiling was used to measure the developing Lung transcriptome in RNA samples derived from 38 normal human Lung tissues at 53 to 154 days post conception. Principal component analysis was used to characterize global expression variation and to identify genes and bioontologic attributes contributing to these variations. Individual gene expression patterns were verified by quantitative reverse transcriptase–polymerase chain reaction analysis.Measurements and Main Results: Gene expression analysis identified attributes not previously associated with Lung Development, such as chemokine-immunologic processes. Lung characteristics attributes (e.g., surfactant function) were observed at an earlier-than-anticipated age. We defined a 3,223 gene developing Lung charact...
Lin Liu - One of the best experts on this subject based on the ideXlab platform.
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Chapter 15 – Lung Development
MicroRNA in Regenerative Medicine, 2015Co-Authors: Lin Liu, Pamela G. Lloyd, Myron E. HinsdaleAbstract:Morphologically, the Lung develops in five stages: embryonic, pseudoglandular, canalicular, saccular, and alveolar. Functionally, this Development is divided into epithelial, endothelial, and mesenchymal Development, each of which is controlled by interconnected transcriptional networks. The incorporation of microRNAs (miRNAs into these networks adds a new layer of regulation and complexity to Lung Development. Several miRNAs have been identified as participating in various aspects of Lung Development, including branching morphogenesis, proliferation, and differentiation of Lung cells. These miRNAs include the miR-17-92 cluster, miR-127, miR-375, and miR-150. miRNA dysregulation may result in Lung diseases.
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Role of GABA Receptors in Fetal Lung Development in Rats
PloS one, 2010Co-Authors: Narendranath Reddy Chintagari, Yang Wang, Nili Jin, Li Gao, Lin LiuAbstract:Fluid accumulation is critical for Lung distension and normal Development. The multi-subunit γ-amino butyric acid type A receptors (GABAA) mainly act by mediating chloride ion (Cl−) fluxes. Since fetal Lung actively secretes Cl−-rich fluid, we investigated the role of GABAA receptors in fetal Lung Development. The physiological ligand, GABA, and its synthesizing enzyme, glutamic acid decarboxylase, were predominantly localized to saccular epithelium. To examine the effect of activating GABAA receptors in fetal Lung Development in vivo, timed-pregnant rats of day 18 gestation underwent an in utero surgery for the administration of GABAA receptor modulators into the fetuses. The fetal Lungs were isolated on day 21 of gestation and analyzed for changes in fetal Lung Development. Fetuses injected with GABA had a significantly higher body weight and Lung weight when compared to phosphate-buffered saline (control)-injected fetuses. GABA-injected fetal Lungs had a higher number of saccules than the control. GABA increased the number of alveolar epithelial type II cells as indicated by surfactant protein C-positive cells. However, GABA decreased the number of α-smooth muscle actin-positive myofibroblasts, but did not affect the number of Clara cells or alveolar type I cells. GABA-mediated effects were blocked by the GABAA receptor antagonist, bicuculline. GABA also increased cell proliferation and Cl− efflux in fetal distal Lung epithelial cells. In conclusion, our results indicate that GABAA receptors accelerate fetal Lung Development, likely through an enhanced cell proliferation and/or fluid secretion.
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The role of pleiotrophin and β-catenin in fetal Lung Development
Respiratory research, 2010Co-Authors: Tingting Weng, Lin LiuAbstract:Mammalian Lung Development is a complex biological process, which is temporally and spatially regulated by growth factors, hormones, and extracellular matrix proteins. Abnormal changes of these molecules often lead to impaired Lung Development, and thus pulmonary diseases. Epithelial-mesenchymal interactions are crucial for fetal Lung Development. This paper reviews two interconnected pathways, pleiotrophin and Wnt/β-catenin, which are involved in fibroblast and epithelial cell communication during fetal Lung Development.
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MicroRNA-127 modulates fetal Lung Development.
Physiological genomics, 2009Co-Authors: Manoj Bhaskaran, Yang Wang, Honghao Zhang, Tingting Weng, Pradyumna Baviskar, Yujie Guo, Deming Gou, Lin LiuAbstract:MicroRNAs (miRNAs) are small endogenous RNAs and are widely regarded as one of the most important regulators of gene expression in both plants and animals. To define the roles of miRNAs in fetal Lung Development, we profiled the miRNA expression pattern during Lung Development with a miRNA microarray. We identified 21 miRNAs that showed significant changes in expression during Lung Development. These miRNAs were grouped into four distinct clusters based on their expression pattern. Cluster 1 contained miRNAs whose expression increased as Development progressed, while clusters 2 and 3 showed the opposite trend of expression. miRNAs in cluster 4 including miRNA-127 (miR-127) had the highest expression at the late stage of fetal Lung Development. Quantitative real-time PCR validated the microarray results of six selected miRNAs. In situ hybridization demonstrated that miR-127 expression gradually shifted from mesenchymal cells to epithelial cells as Development progressed. Overexpression of miR-127 in fetal Lung organ culture significantly decreased the terminal bud count, increased terminal and internal bud sizes, and caused unevenness in bud sizes, indicating improper Development. These findings suggest that miR-127 may have an important role in fetal Lung Development.
Richard Keijzer - One of the best experts on this subject based on the ideXlab platform.
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Abnormal Lung Development in congenital diaphragmatic hernia.
Seminars in pediatric surgery, 2017Co-Authors: Dustin Ameis, Naghmeh Khoshgoo, Richard KeijzerAbstract:The outcomes of patients diagnosed with congenital diaphragmatic hernia (CDH) have recently improved. However, mortality and morbidity remain high, and this is primarily caused by the abnormal Lung Development resulting in pulmonary hypoplasia and persistent pulmonary hypertension. The pathogenesis of CDH is poorly understood, despite the identification of certain candidate genes disrupting normal diaphragm and Lung morphogenesis in animal models of CDH. Defects within the Lung mesenchyme and interstitium contribute to disturbed distal Lung Development. Frequently, a disturbance in the Development of the pleuroperitoneal folds (PPFs) leads to the incomplete formation of the diaphragm and subsequent herniation. Most candidate genes identified in animal models have so far revealed relatively few strong associations in human CDH cases. CDH is likely a highly polygenic disease, and future studies will need to reconcile how disturbances in the expression of multiple genes cause the disease. Herein, we summarize the available literature on abnormal Lung Development associated with CDH.
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MicroRNAs in Lung Development and Disease
Paediatric respiratory reviews, 2016Co-Authors: Dustin Ameis, Naghmeh Khoshgoo, Barbara M. Iwasiow, Phillip Snarr, Richard KeijzerAbstract:MicroRNAs (miRNAs) are small (∼22 nucleotides), non-coding RNA molecules that regulate gene expression post-transcriptionally by inhibiting target mRNAs. Research into the roles of miRNAs in Lung Development and disease is at the early stages. In this review, we discuss the role of miRNAs in pediatric respiratory disease, including cystic fibrosis, asthma, and bronchopulmonary dysplasia.
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MicroRNAs and Lung Development.
Pediatric pulmonology, 2012Co-Authors: Naghmeh Khoshgoo, Ramin Kholdebarin, Barbara M. Iwasiow, Richard KeijzerAbstract:MicroRNAs (miRNAs) constitute a large group of small (∼22 nucleotides), non-coding RNA sequences that are highly conserved among animals, plants and microorganisms, suggesting that microRNAs represent a highly conserved and important regulatory mechanism. They have been demonstrated to play an important role in gene regulation. Recently, miRNAs have become a major focus of interest for research in organ Development. Research focusing on the potential role of microRNAs during Lung Development is slowly starting to emerge. A number of miRNAs have been demonstrated to play important roles during early and late Lung Development. Several studies have begun to profile miRNA expression at various stages of Lung Development and this article provides an overview of the various miRNAs that have been implicated in Lung organogenesis.
