ABL kinase inhibition promotes lung regeneration through expansion of an SCGB1A1+ SPC+ cell population following bacterial pneumonia
Year: 2019
Type: article
Abstract: Significance Approximately 50,000 cases of Staphylococcus aureus pneumonia occur each year. These infections are associated with high mortality rates and frequently progress to multiorgan system failure. Treatment is limited to antibiotics and supportive care. Here we show that Abl kinase inhibition enhances proliferation and differentiation of a subpopulation of lung epithelial cells following pathogen-induced lung injury. We found that a subset of secretory cells in the lower airway expands to sites of injury in the alveolar epithelium to promote regeneration. Mice treated with an Abl kinase inhibitor recovered faster than vehicle control-treated mice following pathogen-induced lung injury. Therapeutic strategies to promote lung epithelial cell regeneration after injury could profoundly improve patient outcomes when used in combination with antibiotics and supportive care.
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Cystic Fibrosis Foundation, University of California, San Diego, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G1563617570, G1632105545, G1917348475, G1959571399, Medical Scientist Training Program, G2806675641, G4928896234, Role of Abl Kinases in immune cell signaling, G542087556, To define the role of SOX9 and Sox9+ cells in alveolar homeostasis and regeneration, G6744250931, G8567026310, UNC Cystic Fibrosis Research and Translation Core Center
OpenAlex ID: W2910276791