A breath of fresh air for emphysema research
2021-07-19
(Press-News.org) Tokyo, Japan - Chronic obstructive pulmonary disease (COPD) causes illness and death worldwide. It is characterized by destruction of the walls of tiny air sacs in the lungs, known as emphysema, and a decline in lung function. Little has been known about the mechanisms by which it begins to develop. But now, researchers from Japan have found a protein that promotes the development of the early stages of emphysema, with the potential to be a therapeutic target.
COPD can be triggered by environmental factors such as cigarette smoking that result in lung inflammation. The development of inflammation involves the movement of molecules inside cells, and this "intracellular trafficking" is known to be associated with some diseases. The team searched for COPD-related proteins that are involved in trafficking and identified a protein called FCHSD1, which is associated with some diseases but with no currently known role in lung function.
It is possible to create a mouse model of emphysema by treating mice with an enzyme called elastase. The team developed a mouse line that was missing the FCHSD1 protein and studied the responses of these mice in comparison with normal mice when emphysema was induced. Normal mice showed a large increase in FCHSD1 after treatment, while mice lacking FCHSD1 were protected from the development of emphysema. These mice showed less airspace expansion owing to damage to the air sacs in the lungs, and had less inflammation and cell death, known as apoptosis.
The researchers went on to investigate the molecular mechanism by which FCHSD1 acts. A protein called NRF2 moves into the nucleus in response to stress and acts to defend against it. However, FCHSD1 binds to NRF2 and prevents it moving into the nucleus. "Mice with a FCHSD1 deficiency showed enhanced nuclear translocation of NRF2 and a smaller reduction in SIRT1 levels, which is seen to occur as emphysema develops," explains lead author Takahiro Kawasaki, "and this reduced inflammation and apoptosis of lung cells."
A potential therapy for COPD could therefore be to increase the activity of NRF2 to counteract FCHSD1. There are treatments currently available that target NRF2, and it may be that inhibiting FCHSD1 at the same time as targeting NRF2 could make these treatments more effective and prevent systemic complications. "Our findings may also lead to a specific therapeutic strategy to ameliorate, or even halt, the progression of emphysema by inhibiting FCHSD1," says Takashi Satoh, senior author of the paper.
COPD is a highly significant disease. The discovery of this mechanism by which FCHSD1 acts to promote the development of emphysema could lead to new treatments for many people.
INFORMATION:
The authors declare no competing interests. This work was supported by: the Japan Science and Technology Agency (JST) through funding for Specially Promoted Research (15H05704), a Grant-in-Aid for Young Scientists (A) (16H06234), a Grant-in-Aid for Challenging Exploratory Research (T17K195570), and a Grant-in-Aid for Scientific Research on Innovative Areas (18H05032); the Visionary Research Fund from Takeda Science Foundation and the Joint research chair of innate immunity supported by Otsuka Pharmaceutical Co., Ltd.; PRIME (17gm6110002h0001), ACT-M (17im0210108h0001), and the Research Program on Hepatitis (18fk0310106h0002 and 1 18fk0210041h0001) from the Japan Agency for Medical Research and Development, AMED.
The article, "Loss of FCHSD1 leads to amelioration of chronic obstructive pulmonary disease", was published in PNAS at DOI: 10.1073/pnas.2019167118.
[Attachments] See images for this press release:
ELSE PRESS RELEASES FROM THIS DATE:
2021-07-19
WINSTON-SALEM, NC, JULY 19, 2021 -- Wake Forest researchers and clinicians are using patient-specific tumor 'organoid' models as a preclinical companion platform to better evaluate immunotherapy treatment for appendiceal cancer, one of the rarest cancers affecting only 1 in 100,000 people. Immunotherapies, also known as biologic therapies, activate the body's own immune system to control, and eliminate cancer.
Appendiceal cancer is historically resistant to systemic chemotherapy, and the effect of immunotherapy is essentially unknown because clinical trials are difficult to perform due to lack of ...
2021-07-19
COLUMBUS, Ohio - When COVID-19 hit, affluent Columbus residents responded by taking significantly fewer trips to large grocery and big-box stores, apparently ordering more online and stocking up when they did go out to shop.
With fewer options available to them, low-income people had to double down on what they had always done: regular trips to the local dollar stores and small groceries to get their family's food.
That's the conclusion of a new study that analyzed traffic to Columbus grocery sellers before, during and after the COVID-19 lockdown.
Dollar stores and small local grocers in neighborhoods housing mostly low-income people of color didn't see as much of a decline in customers during the lockdown as did large grocery and big-box stores, ...
2021-07-19
Tokyo, Japan - Designing materials that have the necessary properties to fulfill specific functions is a challenge faced by researchers working in areas from catalysis to solar cells. To speed up development processes, modeling approaches can be used to predict information to guide refinements. Researchers from The University of Tokyo Institute of Industrial Science have developed a machine learning model to determine characteristics of bonded and adsorbed materials based on parameters of the individual components. Their findings are published in Applied Physics Express.
Factors such as the length and strength of bonds in materials play ...
2021-07-19
Testing of an entire Italian town shows antibody levels remain high nine months after SARS-CoV-2 infection, whether symptomatic or asymptomatic.
Researchers from the University of Padua and Imperial College London tested more than 85 percent of the 3,000 residents of Vo', Italy, in February/March 2020 for infection with SARS-CoV-2, the virus that causes COVID-19, and tested them again in May and November 2020 for antibodies against the virus.
The team found that 98.8 percent of people infected in February/March showed detectable levels of antibodies in November, and there was no difference between people who had suffered symptoms of COVID-19 and those that had been symptom-free. The results are ...
2021-07-19
Why do alterations of certain genes cause cancer only in specific organs of the human body? Scientists at the German Cancer Consortium (DKTK), the Technical University of Munich (TUM), and the University Medical Center Göttingen have now demonstrated that cells originating from different organs are differentially susceptible to activating mutations in cancer drivers: The same mutation in precursor cells of the pancreas or the bile duct leads to fundamental different outcomes. The team discovered for the first time that tissue specific genetic interactions are responsible for the differential susceptibility of the biliary and the pancreatic epithelium towards ...
2021-07-19
The climate crisis will lead to changes in distribution and habitat loss of stony corals in the tropical Atlantic, shows a new study published by the open access publisher Frontiers. The loss of such coral species could have devastating consequences for the marine ecosystems they inhabit. The results of the study highlight an urgent need for coral reef management in the Atlantic.
Researchers at the University of São Paulo projected current and future distributions of three key reef building corals of the tropical Atlantic (Mussismilia hispida, Montastraea cavernosa and the Siderastrea complex). They ...
2021-07-19
To prepare for the next pandemic and provide a coordinated approach to vaccination across the country, Canada should create Canadian Immunization Services based on the Canadian Blood Services model, authors propose in CMAJ (Canadian Medical Association Journal).
The authors, including a leading health policy and immunization expert, a blood system expert and a former federal minister of health, are Dr. Kumanan Wilson, professor, Department of Medicine and member of the Centre for Health Law, Policy and Ethics, University of Ottawa; Dr. Graham Sher, CEO, Canadian Blood Services; and Dr. Jane Philpott, Dean, Faculty of Health Sciences, Queen's University.
"If we want to be better prepared for the ...
2021-07-19
Philadelphia, July 19, 2021 - University of Minnesota School of Public Health researchers recently completed a study to determine how food-insecure young (emerging) adults (18-29 years of age) adapted their eating and child feeding behaviors during the COVID-19 pandemic. The researchers also sought to identify barriers to food access and opportunities to improve local access to resources for emerging adults. Their END ...
2021-07-19
Oncotarget published "Ex vivo analysis of DNA repair targeting in extreme rare cutaneous apocrine sweat gland carcinoma" which reported a rare metastatic case with a PALB2 aberration identified previously as a familial susceptibility gene for breast cancer in the Finnish population.
As PALB2 exhibits functions in the BRCA1/2-RAD51-dependent homologous DNA recombination repair pathway, we sought to use ex vivo functional screening to explore sensitivity of the tumor cells to therapeutic targeting of DNA repair.
Drug screening suggested sensitivity of the PALB2 deficient cells to BET-bromodomain inhibition, and modest ...
2021-07-19
Oncotarget published "Caspase-11 and AIM2 inflammasome are involved in smoking-induced COPD and lung adenocarcinoma" which reported that cigarette smoking is the leading risk factor for COPD and lung cancer establishment.
Epidemiologically, COPD patients are 6.35 times more likely to develop lung cancer.
To mimic COPD, the authors exposed mice to nose-only cigarette smoke and used human samples of lung adenocarcinoma patients according to the smoking and COPD status.
Interestingly, higher expression of AIM2 in non-cancerous tissue of smoking COPD adenocarcinoma patients was correlated to a higher hazard ratio of poor survival ...
LAST 30 PRESS RELEASES:
[Press-News.org] A breath of fresh air for emphysema research
