Promising new target may treat pulmonary fibrosis

By uncovering the mechanism by which fibrous tissue cells in the lung multiply, researchers at The Saban Research Institute of Children's Hospital Los Angeles (CHLA), along with colleagues in Mexico and Canada, have identified a promising new approach for the treatment of pulmonary fibrosis.

Idiopathic pulmonary fibrosis or IPF- where the disease appears spontaneously and without a known cause - is a severe, chronic lung disease in which the rapid growth of fibrous tissue results in increasingly severe breathing difficulties and a high mortality rate.

Excessive signaling of the growth factor TGF-β is recognized as a central player in lung fibrosis, and its increased expression has been identified in both IPF patients and experimental models of the disease. However, in addition to its pro-fibrotic effect, TGF-β signaling is essential to aspects of other systems, such as appropriate immune response.

Therefore, complete therapeutic blockade of TGF-β pathway isn't ideal, says the study's principal investigator Wei Shi, MD, PhD, of the Developmental Biology and Regenerative Medicine research program at CHLA. "This is a very complicated signaling pathway, which promotes mesenchymal stem cell proliferation, while also acting as a tumor suppressant," said Shi, who is also an associate professor in the Department of Surgery, Keck School of Medicine of the University of Southern California. "Our goal was to find a way to target specific cells that result in fibrosis without affecting other cells."

Using a unique transgenic mouse model developed at The Saban Research Institute, the researchers were able to manipulate TGF-β signaling in adult lung mesenchymal cells at selected stages of lung fibrosis. They showed that the progression of fibrosis mediated by TGF-β was independent of early inflammatory processes during initiation of fibrosis - an understanding that is vital in designing therapeutic strategies to stop its progression in IPF patients.

Pulmonary fibrosis is a condition in which the tissue deep in your lungs becomes scarred over time. This tissue gets thick and stiff. That makes it hard for you to catch your breath, and your blood may not get enough oxygen.

Causes of pulmonary fibrosis include environmental pollutants, some medicines, some connective tissue diseases, and interstitial lung disease. Interstitial lung disease is the name for a large group of diseases that inflame or scar the lungs. In most cases, the cause cannot be found. This is called idiopathic pulmonary fibrosis.

Symptoms include

Shortness of breath
A dry, hacking cough that doesn't get better
Fatigue
Weight loss for no known reason
Aching muscles and joints
Clubbing, which is the widening and rounding of the tips of the fingers or toes