Lung fibrosis is a debilitating chronic disease that is caused by scarring in the lungs making it progressively difficult to breathe with some patients requiring supplemental oxygen. According to the Pulmonary Fibrosis Foundation, more than 50,000 new cases are diagnosed annually. Treatment modalities for this disease remain challenging due to the unclear nature of the pathophysiological mechanism of pulmonary fibrosis. Currently, there are no effective treatments except lung transplantation.
Researchers From Standford Study The Mechanism of Lung Fibrosis
Doctor Wernig and colleagues at the Stanford Institute for Stem Cell Biology and Regenerative Medicine recently published their work regarding the mechanism of lung fibrosis. Wernig et al. showed that the fibroblasts proliferate similar to cancer cells by avoiding immune surveillance. Immune surveillance is the mechanism by which the body keeps tissues healthy and eliminates potential disease-causing cells. However, advanced cancerous cells have protective mechanisms to avoid being eaten. One of which, CD47, is used by cancer cells that stop macrophages from taking them up.
Another protective signaling protein is called PD-L1 which keeps macrophages and other cells from attacking them. In idiopathic lung disease, fibroblasts function in a very similar manner as malignant cancer cells. They proliferate to such an extent that they destroy the healthy lung structures, obliterating bronchioles and obstructing the route for air to travel in and out of the circulation.
The Role OF JUN Expression in Lung Fibrosis
In previously published research, Wernig et al. demonstrated that a gene called JUN, a transcription factor, is involved in the progression of pulmonary fibrosis in mice. In the current research, Wernig and colleagues showed that JUN expression in fibroblasts increases the expression of the immune-checkpoint genes CD274 (PD-L1) and CD47. Therefore, the up-regulation of JUN may be a primary contributor to maintaining the progression of fibrosis.
Additionally, the researchers showed increased expression and secretion of an inflammatory molecule called IL-6, which has effects on the immune system. The role of IL-6 and its association with chronic inflammatory disease was well established, but its underlying pathophysiology and its contribution to the process of fibrosis were not clear. Wernig and colleagues also observed that the JUN pathway is also a contributor to increased IL-6 levels which leads to positive feedback thus further amplifying the production of CD47. After blocking the cascade signaling of IL-6 and CD47 simultaneously showed an effective treatment in removing fibrotic cells. The research published by Wernig presents a novel therapeutic approach that can improve the progressive nature of pulmonary fibrosis.