Asthma, COPD Potential New Target - FFA4. The latest results in the journal Science.

Asthma and chronic obstructive pulmonary disease (COPD) are chronic respiratory inflammatory diseases that affect more than 500 million people worldwide and are increasing in incidence.
, however, the control of these diseases by first-line treatment is not yet enough.
For example, in COPD, the combined application of corticosteroids, long-acting toxaline-resistant antagonists, and beta-epinephrine-espressants does not adequately control symptoms and disease exacerbation in many patients.
means that new therapeutic targets need to be identified for these diseases.
An international team of researchers, led by the University of Glasgow, published their latest findings in Science Translational Medicine on 19 August: FFA4, a member of the G protein consonant (GPCR) super-family, promotes respiratory relaxation and eliminates respiratory inflammation and can therefore be used as a target for the treatment of respiratory diseases associated with bronchial contractions and inflammation.
findings pave the way for new treatments for asthma and COPD.
photo source: Science Translational Medicine FFA4 can respond to free circulating fatty acids, including dietary omega-3 fatty acids in fish oil.
previous studies on FFA4 have mostly focused on the regulation of metabolic reactions associated with food intake.
recent studies have shown that FFA4 is expressed in large numbers in pulmonary supersethic cells, and that omega-3 fatty acids, acting through FFA4 litrans, may have some benefits for the repair of the upper octhytal cortical after catreta culture-induced damage.
addition, the role of FFA4 in pulmonary physiology is unclear.
in this study, scientists first used FFA4 selective agonist TUG-1197 and the active agonists TUG-891 for FFA1 and FFA4, and demonstrated FFA4-mediated smooth muscle thoscesia and bronchial dilation in mice.
, the maximum effective concentration of TUG-891 or TUG-1197 in the case of FFA4-mediated smooth muscle relaxation caused the mouse lung slicing gas channel to return to 70% to 80% of the pre-treatment diameter of kabacholine (bronchial shrinkant) (figure below).
image Source: Science Translational Medicine Further experiments have shown that in normal mice, the activation of FFA4 reduces lung resistance.
in mouse models of inflammatory diseases mediated by acute and chronic ozone pollution, house dust mites and cigarette smoke, FFA4 agonists reduced airway resistance, which was not present in mice without FFA4 expression.
TUG-1197 (0.364 mg/ml) was exposed to ozone (3 ppm, 3 hours) in the wild 24 hours before the lung resistance experiment and the bronchial esophation of acetylcholine induction (185 mg/ml) of acetylcholine induction (185 mg/ml) in mice.
(Photo Source: Science Translational Medicine) It's worth noting that FFA4 astrists have also been shown to significantly improve airway high reactivity and inflammation in mouse models of multiple respiratory diseases.
study, scientists also found FFA4 in human lung tissue, similar to what was observed in mice.
and FFA4 agitants also mediat the physiasics of the estosome smooth muscles.
microscopic image of the representative biopsy of the human bronch pipe.
ec-cortical cell layer, ASM-channel smooth muscle, LP-inherent layer.
(Photo Source: Science Translational Medicine) Finally, the study reveals that one of FFA4's mechanisms for smooth muscle relaxation in mice's gas ducts are released through prosultin E2 (PGE2), which is then mediated by EP2 prosthyroids.
, the study showed that FFA4 was expressed in mouse lung tissue under normal physiological conditions and mediated smooth muscle dilation of the tragasmi.
in respiratory disease models, FFA4 mediated airway smooth muscle relaxation and anti-inflammatory effects.
, the applicability of mouse studies to human diseases has also been validated.
data to support the long-chain free fatty acids- and fatty acids-borne FFA4 may be the target for treating airway diseases associated with bronchial contraction and inflammation.
Andrew Tobin, co-author of the paper, said: "We were surprised to be able to target a protein that has until now been thought to be activated by fish oil in the diet, relaxing airway muscles and preventing inflammation.
we are optimistic that by expanding this research, it will be possible to develop a new drug for asthma and COPD.
" Reference: 1 s new class of drugs reverses symptoms of asthma in animal models (Source: Medical press) 2 s Rudi Prihandoko et al. Pathophysio regulation of lung function by the free fatty acid receptor FFA4, Science Translational Medicine (2020). DOI: 10.1126/scitranslmed.aaw9009.