Molecular analysis identifies key differences in lungs of cystic fibrosis patients

A team of researchers from UCLA, Cedars-Sinai and the Cystic FibrosisFoundation has developed a first-of-its-kind molecular catalog of cells in healthy lungs and the lungs of people with cystic fibrosis.The catalog,described today in the journal Nature Medicine, reveals new subtypes of cells and illustrates how the disease changes the cellular makeup of the airways. The findings could help scientists in their search for specific cell types that represent prime targets for genetic and cell therapies for cystic fibrosis.“This new research has provided us with valuable insights into the cellular makeup of both healthy and diseased airways,”said Dr. Brigitte Gomperts, a co-senior author of the study and a member of the  Eli and Edythe Broad Center of  Regenerative Medicine and Stem Cell Research at UCLA.“If you can understand how things work in a state of health, it becomes easier to see what cellular and molecular changes occur in a disease state.”A progressive genetic disorder that affects more than 70,000 people worldwide, cystic fibrosis results from mutations to the CFTR gene. Cells that contain the defective protein encoded by the gene produce unusually thick and sticky mucus that builds up in the lungs and other organs.  This mucus clogs the airways, trapping germs and bacteria that can cause life-threatening infections and irreversible lung damage.While several new therapies can partially restore the function of these damaged pr...
Source: UCLA Newsroom: Health Sciences - Category: Universities & Medical Training Source Type: news

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Source: Epigenetics - Category: Genetics & Stem Cells Authors: Source Type: research
Airway epithelium forms a physical barrier that protects the lung from the entrance of inhaled allergens, irritants, or microorganisms. This epithelial structure is maintained by tight junctions, adherens junctions and desmosomes that prevent the diffusion of soluble mediators or proteins between apical and basolateral cell surfaces. This apical junctional complex also participates in several signaling pathways involved in gene expression, cell proliferation and cell differentiation. In addition, the airway epithelium can produce chemokines and cytokines that trigger the activation of the immune response. Disruption of thi...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Autophagy. 2021 Apr 27:1-18. doi: 10.1080/15548627.2021.1909406. Online ahead of print.ABSTRACTMacroautophagy/autophagy is a cellular catabolic process that results in lysosome-mediated recycling of organelles and protein aggregates, as well as the destruction of intracellular pathogens. Its role in the maintenance of the intestinal epithelium is of particular interest, as several autophagy-related genes have been associated with intestinal disease. Autophagy and its regulatory mechanisms are involved in both homeostasis and repair of the intestine, supporting intestinal barrier function in response to cellular stress thro...
Source: Autophagy - Category: Cytology Authors: Source Type: research
Abstract The use of synthetic ion transporters for alteration of the concentration of ions across cell membranes has drawn attention from scientists over the last two decades. This ion transport property has been sensibly used to reduce the viability of cancer cells mainly due to the disruption of their ion homeostasis, leading to the perturbation of their abnormal pH gradient. The use of the proanionophore strategy has been recently adopted to increase cellular deliverability and reduce unwanted cytotoxicity towards normal cells. Meanwhile, various anionophores exhibiting non-toxic behavior in epithelial cells ha...
Source: Chemical Communications - Category: Chemistry Authors: Tags: Chem Commun (Camb) Source Type: research
Abstract Respiratory diseases are one of the prime topics of concern in the current era due to improper diagnostics tools. Gene-editing therapy like Clustered regularly interspaced palindromic repeats-associated nuclease 9 (CRISPR/Cas9) is gaining popularity in pulmonary research opening up doors to invaluable insights on underlying mechanisms. CRISPR/Cas9 can be considered as a potential gene editing tool with a scientific community that is helping in the advancement of knowledge in respiratory health and therapy. As an appealing therapeutic tool, we hereby explore the advanced research on the application of CRIS...
Source: Current Gene Therapy - Category: Genetics & Stem Cells Authors: Tags: Curr Gene Ther Source Type: research
Tyrosine kinase inhibitors directed to the receptor for epidermal growth factor (EGFr TKIs) reverse the inhibitory effect of EGF on calcium ‐dependent chloride secretion across intestinal epithelial cells and potentiate secretory responses to carbachol (CCh). In addition, these drugs have a deleterious effect on barrier function. These effects likely contribute synergistically to the ability of EGFr TKIs to induce diarrhea. CCh activa ted ERK phosphorylation in a manner that was relatively insensitive to EGFr TKIs and delayed the deleterious effects of the drugs on barrier function. CaCC, calcium‐dependent chloride ion...
Source: Physiological Reports - Category: Physiology Authors: Tags: ORIGINAL RESEARCH Source Type: research
Lung diseases constitute a global health concern causing disability. According to WHO in 2016, respiratory diseases accounted for 24% of world population mortality, the second cause of death after cardiovascular diseases. The Kv7 channels family is a group of voltage-dependent K+ channels (Kv) encoded by KCNQ genes that are involved in various physiological functions in numerous cell types, especially, cardiac myocytes, smooth muscle cells, neurons, and epithelial cells. Kv7 channel α-subunits are regulated by KCNE1–5 ancillary β-subunits, which modulate several characteristics of Kv7 channels such as biop...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Abstract OBJECTIVES: Family with sequence similarity 13 member A (FAM13A) genetic variants have been associated with several chronic respiratory diseases including chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF) and lung cancer. The FAM13A protein includes a RhoGTPase activating protein (RhoGAP) domain known to participate in various cellular mechanisms including cell proliferation. While intensive genomic studies have been performed to reveal its involvement in lung diseases, the biological role of FAM13A protein is still not completely elucidated. RESU...
Source: Cell Research - Category: Cytology Authors: Tags: BMC Res Notes Source Type: research
Abstract E74-like factor 5 (ELF5) and ETS-homologous factor (EHF) are epithelial selective ETS family transcription factors (TFs) encoded by genes at chr11p13, a region associated with cystic fibrosis (CF) lung disease severity. EHF controls many key processes in lung epithelial function so its regulatory mechanisms are important. Using CRISPR/Cas9 technology, we removed three key cis-regulatory elements (CREs) from the chr11p13 region and also activated multiple open chromatin sites with CRISPRa in airway epithelial cells. Deletion of the CREs caused subtle changes in chromatin architecture and site-specific incr...
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research
Dysfunction of the pancreas is related to a number of diseases, most famously diabetes. Conditions such as cystic fibrosis-related diabetes (CFRD), are particularly difficult to study in a laboratory setting, but researchers at Cincinnati Children&rs...
Source: Medgadget - Category: Medical Devices Authors: Tags: Materials Medicine Source Type: blogs
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