Abstract
Unleashing rapamycin in fibrosis.
Highlights
Rapamycin is a macrocyclic antibiotic produced by the bacteria streptomyces hygroscopicus, with immunosuppressive and antiproliferative capabilities
While fibroblasts are thought to represent the end effector cell in laryngotracheal stenosis (LTS), by the time increased collagen deposition results in clinical stenosis of the larynx and trachea it is too late to effectively intervene medically, committing these patients to repeated surgical dilation and/or excision of fibrosis with the morbidity associated with invasive surgical procedures
In another study by our laboratory, we demonstrated scar fibroblasts were highly proliferative compared to normal fibroblasts yet used the inefficient metabolic process of aerobic glycolysis to preferentially drive hyperplasia to form scar
Summary
Rapamycin (sirolimus, rapamine) is a macrocyclic antibiotic produced by the bacteria streptomyces hygroscopicus, with immunosuppressive and antiproliferative capabilities. The excessive collagen deposition results in organ-specific injury, which in LTS manifests as airway obstruction and clinical dyspnea. While fibroblasts are thought to represent the end effector cell in LTS, by the time increased collagen deposition results in clinical stenosis of the larynx and trachea it is too late to effectively intervene medically, committing these patients to repeated surgical dilation and/or excision of fibrosis with the morbidity associated with invasive surgical procedures.
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