Abi1 mediates airway smooth muscle cell proliferation and airway remodeling via Jak2/STAT3 signaling

Asthma is a complex pulmonary disorder with multiple pathological mechanisms. A key pathological feature of chronic asthma is airway remodeling, which is largely attributed to airway smooth muscle (ASM) hyperplasia that contributes to thickening of the airway wall and further drives asthma pathology. The cellular processes that mediate ASM cell proliferation are not completely elucidated. Using multiple approaches, we demonstrate that the adapter protein Abi1 (Abelson interactor 1) is upregulated in similar to 50% of ASM cell cultures derived from patients with asthma. Loss-of-function studies demonstrate that Abi1 regulates the activation of Jak2 (Janus kinase 2) and STAT3 (signal transducers and activators of transcription 3) as well as the proliferation of both nonasthmatic and asthmatic human ASM cell cultures. These findings identify Abi1 as a molecular switch that activates Jak2 kinase and STAT3 in ASM cells and demonstrate that a dysfunctional Abi1-associated pathway contributes to the progression of asthma.

Automated summary

Asthma is a complex pulmonary disorder with multiple pathological mechanisms. A key pathological feature is airway remodeling, which is largely caused by the abnormal proliferation of airway smooth muscle cells. An adapter protein called Abi1 has been identified as a molecular switch that regulates the activation of certain proteins and contributes to the progression of asthma.