Fig. 10.
Inflammatory cytokines induce ROS generation in hASM that leads to ER/SR stress with downstream impact of reduced Mfn2 expression (increased Drp1), uncoupling of mitochondria to the ER/SR membrane, decreased [Ca2+]mito buffering, which contributes to increased [Ca2+]cyt and force responses to ACh stimulation (hyper-reactive state). A decrease in [Ca2+]mito buffering also leads to mitochondrial dysfunction and a further increase in ROS generation. Reduced Mfn2 expression also leads to mitochondrial fragmentation (fission) and increased cell proliferation and remodeling (synthetic state). ROS, reactive oxidant species; hASM, human airway smooth muscle cells; ER/SR, endoplasmic reticulum/sarcoplasmic reticulum; ACh, acetycholine; Mfn2, mitofusin-2; Drp1, dynamin related protein 1.