Pulmonary arterial hypertension (PAH) is caused, in part, because of an imbalance between anti- and pro-proliferative cellular signaling pathways. Cell proliferation, or the growth and maturation of a cell, is an important process that happens throughout the body. The TGF-beta superfamily plays an important role in managing these pathways – the ones that say “grow” and “stop growing.” In PAH, this imbalance affects the structure of the lung’s blood vessels, which leads to the primary symptoms of the disease.
Fibrosis, the hallmark symptom of systemic sclerosis, and what eventually leads to interstitial lung disease, is yet another process that is regulated by the TGF-beta superfamily. Known for its role in wound repair, the TGF-beta 1 pathway is responsible for promoting the proliferation of myofibroblasts, who in turn, build scar tissue. When the release of TGF-beta decreases, the myofibroblasts continue in their standard life cycle, ending in apoptosis. This planned cell death brings an end to the production of scar tissue, and the wound is allowed to heal normally. If TGF-beta is continuously secreted, the myofibroblasts continue to produce scar tissue unchecked, an aberrant behavior known as fibrosis. The overactivity of this TGF-beta pathway is responsible for fibrosis, which accumulates on the alveoli in the lungs. By limiting the secretion of TGF-beta, the pathological production of scar tissue can be slowed, and healthy respiration and circulation can resume.