A discovery in the Duke-Nus School of Medicine offers a new hope in the battle against pulmonary fibrosis, a weakening lung condition that progressively makes it more difficult for patients to breathe. Scientists have identified proteins in immune cells that, when blocked, could significantly reduce lung tissue healing.
Current treatments mainly control symptoms and improve the quality of life, without addressing the underlying cause of pulmonary fibrosis.
Although macrophages, an immune cell type, it was previously known to contribute to inflammation and scars in pulmonary fibrosis, the underlying mechanisms were not clear. After discovering that two proteins in macrophages, YAP and Taz, are involved in heart scars, school researchers sought to determine if these proteins play a similar role in the lungs and better understand how their activity influences the progression of the disease.
YAP and Taz are part of a critical molecular path that generally helps cells grow and repair. However, in a preclinical pulmonary fibrosis model, researchers discovered that these proteins can also contribute to harmful scars.
In his study, published in the European respiratory magazine, The researchers found that blocking YAP and Taz can stop the formation of scars and restore the immediate environment to one that fosters the regeneration of three ways:
Expanding a strong call to the arms: YAP and Taz drive inflammation by amplifying the effect of a molecule called CCL2. As a reference beacon, this signaling molecule attracts several immune cells to the affected areas of the lungs during lesions. However, when the lungs are recruited in excess, these immune cells can damage the organs by causing unofficial inflammation, which leads to tissue scars. The interruption of the connection between the two and CCL2 proteins reduces the number of recruited immune cells, which drives tissue scars.
Maintain a relationship of healthy immune cells: YAP and TAZ can damage the lungs by increasing inflammatory levels of immune cells, amplifying tissue inflammation. When these proteins are eliminated, immune cells that help repair and regenerate damaged tissue exceed their inflammatory counterparts, reducing pulmonary inflammation and allowing the organ to heal more effectively.
By interrupting the communication of proteins with a nearby path: these proteins can also exacerbate pulmonary fibrosis by influencing macrophages with fibroblasts, which are nearby cells that are key to repair damaged tissue and maintain the structure of the organs . The unregulated macrophage activity indicates excessively fibroblasts to respond to a lung injury, which leads to tissue scars. The inhibition of YAP and Taz interrupts communication between macrophages and fibroblasts, reducing damage to the lungs.
The main research scientist of Dr. MD Masum Mia of the Duke-Nus Metabolic and Metabolic Disorders Program, the first author of the study, said about the findings:
“This advance not only deepens our understanding of the specific molecular mechanisms responsible for pulmonary fibrosis, but could also lead to treatments that stop or even reinvest the pulmonary scars in the disease.”
Racing the way for new treatment options for pulmonary fibrosis
Global early phase clinical trials for novel therapies that go to YAP and Taz in Cancers, which are characterized by inflammation and immune scars, are underway, and the research team is exploring whether such therapies are viable for treating patients with fibrosis pulmonary.
The associated professor Manvendra Kumar Singh of the Duke-Nus cardiovascular and metabolic disorders program, lead author of the study, said about the next steps for the project:
“Pulmonary fibrosis is strongly linked to the unregulated activity of immune and connective tissue, as well as the loss of epithelial cells. By deepening these interactions that drive tissue scars, we can obtain deeper ideas and discover objectives Potential therapy for treatment. We will validate even more the roles of YAP and Taz in the disease and confirm the effectiveness of the therapies that inhibit these proteins, offering patients better results. “
In addition to pulmonary fibrosis, YAP and Taz are also involved in cardiac, liver and renal fibrosis, suggesting that therapies aimed at these proteins could offer a broader therapeutic potential for a range of fibrotic diseases.
Professor Patrick Tan, Senior Vice President of Research at Duke-Nus, commented:
“When focusing on the root causes of fibrosis, our new therapeutic approach offers the potential not only to handle, but also stop significantly or reverse the progression of pulmonary fibrosis. This advance could drastically improve the results of patients, reduce costs of long -term medical care and, finally, improve life expectancy and quality for patients worldwide. “
This new research, part of Duke-Nus’s efforts to develop biomedical solutions that improve patients’ lives, has the support of the National Research Foundation, Singapore, under the subsidy of open funds investigation of the National Research Council Medical (NMRC) (MOH-001625) and the individual investigation subsidy of open funds (MOH-001130) and administered by the Ministry of Health of Singapore through The NMRC office, Moh Holdings Pte Ltd.