| First Author | Johnson MT | Year | 2022 |
| Journal | Proc Natl Acad Sci U S A | Volume | 119 |
| Issue | 1 | PubMed ID | 34949717 |
| Mgi Jnum | J:326316 | Mgi Id | MGI:6861767 |
| Doi | 10.1073/pnas.2114557118 | Citation | Johnson MT, et al. (2022) STIM1 is a core trigger of airway smooth muscle remodeling and hyperresponsiveness in asthma. Proc Natl Acad Sci U S A 119(1):e2114557118 |
| abstractText | Airway remodeling and airway hyperresponsiveness are central drivers of asthma severity. Airway remodeling is a structural change involving the dedifferentiation of airway smooth muscle (ASM) cells from a quiescent to a proliferative and secretory phenotype. Here, we show up-regulation of the endoplasmic reticulum Ca(2+) sensor stromal-interacting molecule 1 (STIM1) in ASM of asthmatic mice. STIM1 is required for metabolic and transcriptional reprogramming that supports airway remodeling, including ASM proliferation, migration, secretion of cytokines and extracellular matrix, enhanced mitochondrial mass, and increased oxidative phosphorylation and glycolytic flux. Mechanistically, STIM1-mediated Ca(2+) influx is critical for the activation of nuclear factor of activated T cells 4 and subsequent interleukin-6 secretion and transcription of pro-remodeling transcription factors, growth factors, surface receptors, and asthma-associated proteins. STIM1 drives airway hyperresponsiveness in asthmatic mice through enhanced frequency and amplitude of ASM cytosolic Ca(2+) oscillations. Our data advocates for ASM STIM1 as a target for asthma therapy. |
