Study suggests lung fibrosis reversal using body's natural healing process

A recent study from a team led by Sean Fortier, M.D. and Marc Peters-Golden, M.D. of the Division of Pulmonary and Critical Care Medicine at the University of Michigan Medical School uncovered a pathway used during normal wound healing that has the potential to reverse idiopathic pulmonary fibrosis (IPF).

The most common type of lung fibrosis — scarring of the lungs -- is idiopathic, meaning of unknown cause. It is a chronic and progressive lung disease characterized by the gradual scarring and stiffening of lung tissue. The process by which lung injury either leads to healing or fibrosis relies in part on what happens to a cell called a fibroblast, which forms connective tissue.

During injury or illness, fibroblasts are activated, becoming myofibroblasts that form scar tissue by secreting collagen. When the job is done, these fibroblasts must be deactivated, or de-differentiated, to go back to their quiet state or undergo programmed cell death and be cleared.

In the study, using a mouse model, researchers simulated IPF by administering bleomycin, a chemotherapy agent that causes cell injury and confirmed that the resulting lung scarring resolved itself over about six weeks. By genetically eliminating MKP1 in fibroblasts of mice after establishing lung injury, the team saw that fibrosis continued uncontrolled. They also performed several additional studies using CRISPR techniques.

“This is the major distinction between normal wound healing and fibrosis – the persistence of activated myofibroblasts. That deactivation is controlled by molecular brakes. The study examined one of these brakes, called MKP1 – which the team found was expressed at lower levels in the fibroblasts of patients with IPF. We argued by contradiction: when you knock out this brake, fibrosis that would otherwise naturally disappear, persists and therefore MKP1 is necessary for spontaneous resolution of fibrosis.That’s totally in keeping with the fact that they do slow the progression, but they don’t halt or reverse disease,” said Fortier.